Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate si...Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.展开更多
The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tu...The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.展开更多
SARS-CoV-2 has triggered a public health outbreak across the world, resulting in almost 5 million deaths as of January 2022. The arrival of vaccines has provided temporary relief, but these vaccines target the spike p...SARS-CoV-2 has triggered a public health outbreak across the world, resulting in almost 5 million deaths as of January 2022. The arrival of vaccines has provided temporary relief, but these vaccines target the spike protein, which is highly prone to mutation, making it impossible to develop a long-term cure for the coronavirus. As such, there is an urgent need for site-specific inhibition of the virus in the respiratory tract, as well as targeting the internal proteins of the virus itself. Past literature has identified 3CLpro and PLpro as enzymes essential to the replication of the virus, as they assemble almost the entirety of the viral genome;as such, inhibiting the activity of these enzymes can stymie the spread of the virus. This project proposes the use of inhaled drug delivery to inhibit Covid-19 by synthesizing a formulation that can travel directly to the lungs via inhalation. In order to streamline synthesis, existing FDA-approved drugs were analyzed using computational docking software and in vitro assays for inhibitory activity against these two enzymes. High-performing drugs were then encapsulated in PLGA nanoparticles to synthesize a drug delivery system, which was tested and characterized in vitro. Furthermore, in an effort to improve this drug delivery system relative to other drug delivery systems, the use of enzyme nanomotors was explored as a way to increase the accuracy of delivery by using computational simulations that mimicked conditions in the human body to model the velocity and trajectory of the nanomotors.展开更多
In the past decades,many materials have been studied as carriers for targeted drug delivery.However,there is a need for utilizable and selective carrier materials with few side effects.Here,the magnetic Ganoderma Luci...In the past decades,many materials have been studied as carriers for targeted drug delivery.However,there is a need for utilizable and selective carrier materials with few side effects.Here,the magnetic Ganoderma Lucidum Spores(mGLS)as a highly efficient targeted drug delivery carrier were explored.Then the regulatable targeted drug delivery system was verified by loading and releasing of the 5-Fluorouracil(5-FU).The results showed that the maximum of the loaded 5-FU reached 250.23 mg·g^(−1)in the mGLS.The cumulative release of the 5-FU for the drug delivery system could reach 80.11%and 67.14%in the PBS and HCl after 48 h,respectively.In addition,this system showed the good pharmacokinetic properties in vivo.After 12 h,the blood concentration in the 5-FU@mGLS group kept at 5.3µg·mL^(−1)and was four times higher than that in the 5-FU group.In summary,the GLS as a natural microscale core-shell structures appears the striking application in carrier material for oral drug delivery.展开更多
Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescen...Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.展开更多
Aminopeptidase N(APN)/CD13 is a transmembrane glycoprotein,which is overexpressed on tumor neovascular endothelial cells and most tumor cells,where it plays an important role in tumor angiogenesis.Peptides containing ...Aminopeptidase N(APN)/CD13 is a transmembrane glycoprotein,which is overexpressed on tumor neovascular endothelial cells and most tumor cells,where it plays an important role in tumor angiogenesis.Peptides containing the Asn-Gly-Arg(NGR)motif can specifically recognize APN/CD13 allowing them to act as tumor-homing peptides for the targeted delivery of anti-tumor drugs to tumor neovascular endothelial cells and tumor cells.This article reviews the literature and recent developments related to APN/CD13,its role in tumor growth and some antitumor drug delivery systems containing NGR peptides designed to target APN/CD13.展开更多
The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of...The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.展开更多
Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resi...Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.展开更多
Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic ...Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.展开更多
A novel light responsive nanosphere was constructed,and it was used as a drug carrier to investigate the loading and release properties of the Quercetin(QU).In this paper,mesoporous silica nanoparticles(MSN)were used ...A novel light responsive nanosphere was constructed,and it was used as a drug carrier to investigate the loading and release properties of the Quercetin(QU).In this paper,mesoporous silica nanoparticles(MSN)were used as a substrate,and 3-aminopropyl triethyoxysilane was used as a surface modification agent to introduce—NH_(2),and the azobenzene-4,4’-dicarboxylic acid(AZO)was used as light responsive agent to introduce the group of—N=N—,and thenβ-cyclodextrin(β-CD)was combined with AZO through host-guest interaction to construct light responsive nanoparticles(MSN@β-CD).The structure and properties of the carrier were analyzed by FTIR,BET,XPS,TGA,XRD,SEM and TEM.In vitro drug release studies showed the release rate of QU@MSN@β-CD(dark)was 12.19%within 72 h,but the release rate of QU@MSN@β-CD(light 10 min)was 26.09%,exhibiting a light-responsive property.The CCK8 tests demonstrated that MSN@β-CD could significantly decrease the toxicity of QU.Therefore,the controllable light-responsive drug delivery system has great application prospects.展开更多
Drug delivery via intra-articular(IA)injection has proved to be effective in osteoarthritis(OA)therapy,limited by the drug efficiency and short retention time of the drug delivery systems(DDSs).Herein,a series of modi...Drug delivery via intra-articular(IA)injection has proved to be effective in osteoarthritis(OA)therapy,limited by the drug efficiency and short retention time of the drug delivery systems(DDSs).Herein,a series of modified cross-linked dextran(Sephadex,S0)was fabricated by respectively grafting with linear alkyl chains,branched alkyl chains or aromatic chain,and acted as DDSs after ibuprofen(Ibu)loading for OA therapy.This DDSs expressed sustained drug release,excellent anti-inflammatory and chondroprotective effects both in IL-1βinduced chondrocytes and OA joints.Specifically,the introduction of a longer hydrophobic chain,particularly an aromatic chain,distinctly improved the hydrophobicity of S0,increased Ibu loading efficiency,and further led to significantly improving OA therapeutic effects.Therefore,hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.展开更多
Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and inflammation.Nevertheless,current therapeutic regimens are inadequate to promptly address the vast diversity...Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and inflammation.Nevertheless,current therapeutic regimens are inadequate to promptly address the vast diversity of potential pathogens.Omiganan,an antimicrobial peptide,has shown promise for neutralizing endotoxins and eliminating diverse pathogens.However,its clinical application is hindered by safety and stability concerns.Herein,we present a nanoscale drug delivery system(Omi-hyd-Dex@HA NPs)that selectively targets infectious microenvironments(IMEs)and responds to specific stimuli for efficient intervention in sepsis.The system consists of omiganan-dexamethasone conjugates linked by hydrazone bonds which self-assemble into nanoparticles coated with a hyaluronic acid(HA).The HA coating not only facilitates IMEs-targeting through interaction with intercellular-adhesion-molecule-1 on inflamed endotheliocytes,but also improves the biosafety of the nanosystem and enhances drug accumulation in primary infection sites triggered by hyaluronidase.The nanoparticles release dual drugs in IMEs through pH-sensitive cleavage of hydrazone bonds to eradicate pathogens and suppress inflammation.In multiple tissue infection and sepsis animal models,Omi-hyd-Dex@HA NPs exhibited rapid source control and comprehensive inflammation reduction,thereby preventing subsequent fatal complications and significantly improving survival outcomes.The bio-responsive and self-delivering nanosystem offers a promising strategy for systemic sepsis treatment in emergencies.展开更多
Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective deli...Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.展开更多
The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptom...The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.展开更多
With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of res...With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of respiratory diseases,clinical intervention is still mainly based on drug control of pulmonary symptoms.However,systemic drugs have disadvantages such as many adverse reactions and severe systemic side effects.In recent years,the research and development of local drug delivery systems for the respiratory tract has brought new changes to the treatment of respiratory diseases.Locally delivered drugs can directly act on the airways and have the characteristics of fast onset,good curative effect and small side effects.It is a simple,efficient and safe treatment method,which has a very significant effect,and has become a hot topic of current research and promotion.This paper briefly reviews the development track and latest research progress of respiratory local drug delivery systems at home and abroad,in order to provide reference for clinical workers in drug selection and application.展开更多
The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of lif...The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of life,but also imposes a substantial burden on the healthcare system.In spite of efforts made in clinical practice,treating DFU remains a challenging task.While mesenchymal stem cell(MSC)therapy has been extensively studied in treating DFU,the current efficacy of DFU healing using this method is still inadequate.However,in recent years,several MSCs-based drug delivery systems have emerged,which have shown to increase the efficacy of MSC therapy,especially in treating DFU.This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.展开更多
The number of people with eye diseases has increased with the use of electronics.However,the bioavailability of eye drops remains low owing to the presence of the ocular barrier and other reasons.Although many drug de...The number of people with eye diseases has increased with the use of electronics.However,the bioavailability of eye drops remains low owing to the presence of the ocular barrier and other reasons.Although many drug delivery systems have been developed to overcome these problems,they have certain limitations.In recent years,the development of contact lenses that can deliver drugs for long periods with high bioavailability and without affecting vision has increased the interest in using contact lenses for drug delivery.Hence,a review of the current state of research on drug delivery contact lenses has become crucial.This article reviews the key physical and chemical properties of drug-laden contact lenses,development and classification of contact lenses,and features of the commonly used materials.A review of the methods commonly used in current research to create contact lenses has also been presented.An overview on how drug-laden contact lenses can overcome the problems of high burst and short release duration has been discussed.Overall,the review focuses on drug delivery methods using smart contact lenses,and predicts the future direction of research on contact lenses.展开更多
BACKGROUND Intractable postherpetic neuralgia(PHN)can be difficult to manage even with aggressive multimodal therapies.Patients who experience uncontrolled refractory cranial PHN despite conservative treatment may ben...BACKGROUND Intractable postherpetic neuralgia(PHN)can be difficult to manage even with aggressive multimodal therapies.Patients who experience uncontrolled refractory cranial PHN despite conservative treatment may benefit from an intrathecal drug delivery system(IDDS).For craniofacial neuropathic pain,the traditional approach has been to place the intrathecal catheter tip below the level of the cranial nerve root entry zones,which may lead to insufficient analgesia.CASE SUMMARY We describe a 69-year-old man with a 1-year history of PHN after developing a vesicular rash in the ophthalmic division of cranial nerve V(trigeminal nerve)distribution.The pain was rated 7-8 at rest and 9-10 at breakthrough pain(BTP)on a numeric rating scale.Despite receiving aggressive multimodal therapies including large doses of oral analgesics(gabapentin 150 mg q12 h,oxycodone 5 mg/acetaminophen 325 mg q6 h,and lidocaine 5%patch 700 mg q12 h)and sphenopalatine ganglion block,there was no relief of pain.Subsequently,the patient elected to have an implantable IDDS with the catheter tip placed at the interpeduncular cistern.The frequency of BTP episodes decreased.The patient’s continuous daily dose was adjusted to 0.032 mg/d after 3 mo of follow-up and stopped 5 mo later.He did not report pain or other discomfort at outpatient follow-up 6 mo and 1 year after stopping intracisternal hydromorphone.CONCLUSION The use of interpeduncular cistern intrathecal infusion with low-dose hydromorphone by IDDS may be effective for severe craniofacial PHN.展开更多
Inflammatory bowel disease(IBD)is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization.With no curative therapy for IBD at present,the development of effective therapeutics...Inflammatory bowel disease(IBD)is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization.With no curative therapy for IBD at present,the development of effective therapeutics is highly advocated.Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention(EPR)effect caused by the inflammation.However,the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release.Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs,ligandmodified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects.This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands.Finally,challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.展开更多
The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid(HGA) conjugate for intravenous paclitaxel(PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles(PTX/HGA...The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid(HGA) conjugate for intravenous paclitaxel(PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles(PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio(TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects.展开更多
基金supported by the Deputy Research and Technology, Ardabil University of Medical Sciences。
文摘Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education (No. 20110071130011)the National Science and Technology Major Project (No. 2012ZX09304004)
文摘The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.
文摘SARS-CoV-2 has triggered a public health outbreak across the world, resulting in almost 5 million deaths as of January 2022. The arrival of vaccines has provided temporary relief, but these vaccines target the spike protein, which is highly prone to mutation, making it impossible to develop a long-term cure for the coronavirus. As such, there is an urgent need for site-specific inhibition of the virus in the respiratory tract, as well as targeting the internal proteins of the virus itself. Past literature has identified 3CLpro and PLpro as enzymes essential to the replication of the virus, as they assemble almost the entirety of the viral genome;as such, inhibiting the activity of these enzymes can stymie the spread of the virus. This project proposes the use of inhaled drug delivery to inhibit Covid-19 by synthesizing a formulation that can travel directly to the lungs via inhalation. In order to streamline synthesis, existing FDA-approved drugs were analyzed using computational docking software and in vitro assays for inhibitory activity against these two enzymes. High-performing drugs were then encapsulated in PLGA nanoparticles to synthesize a drug delivery system, which was tested and characterized in vitro. Furthermore, in an effort to improve this drug delivery system relative to other drug delivery systems, the use of enzyme nanomotors was explored as a way to increase the accuracy of delivery by using computational simulations that mimicked conditions in the human body to model the velocity and trajectory of the nanomotors.
基金This work was supported by National Key R&D Program of China(No.2018YFB1105400)Jilin Provincial Science and Technology Program(Nos.20190702002GH,2020C022-1,and YDZJ202102CXJD 007)Programme of Introducing Talents of Discipline to Universities(D17017).
文摘In the past decades,many materials have been studied as carriers for targeted drug delivery.However,there is a need for utilizable and selective carrier materials with few side effects.Here,the magnetic Ganoderma Lucidum Spores(mGLS)as a highly efficient targeted drug delivery carrier were explored.Then the regulatable targeted drug delivery system was verified by loading and releasing of the 5-Fluorouracil(5-FU).The results showed that the maximum of the loaded 5-FU reached 250.23 mg·g^(−1)in the mGLS.The cumulative release of the 5-FU for the drug delivery system could reach 80.11%and 67.14%in the PBS and HCl after 48 h,respectively.In addition,this system showed the good pharmacokinetic properties in vivo.After 12 h,the blood concentration in the 5-FU@mGLS group kept at 5.3µg·mL^(−1)and was four times higher than that in the 5-FU group.In summary,the GLS as a natural microscale core-shell structures appears the striking application in carrier material for oral drug delivery.
基金supported by Dalian Youth Science and Technology Star Project(2020RQ121)the National Science Fund for Distinguished Young Scholars of China(31925031)+1 种基金Doctoral Scientific Research Foundation of Liaoning Province(2020-BS-211)Liaoning Province Education Administration(J2020101)。
文摘Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.
基金This research was supported by the National Basic Research Program of China(No.2009CB930300)State Key Projects(No.2009ZX09310-001)the 863 Project(No.2007AA021811).
文摘Aminopeptidase N(APN)/CD13 is a transmembrane glycoprotein,which is overexpressed on tumor neovascular endothelial cells and most tumor cells,where it plays an important role in tumor angiogenesis.Peptides containing the Asn-Gly-Arg(NGR)motif can specifically recognize APN/CD13 allowing them to act as tumor-homing peptides for the targeted delivery of anti-tumor drugs to tumor neovascular endothelial cells and tumor cells.This article reviews the literature and recent developments related to APN/CD13,its role in tumor growth and some antitumor drug delivery systems containing NGR peptides designed to target APN/CD13.
文摘The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.
基金supported by the National Key R&D Program of China(Grant No.2022YFC3401404)the National Natural Science Foundation of China(Grant Nos.32170935 and 31930066).
文摘Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.
文摘Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.
文摘A novel light responsive nanosphere was constructed,and it was used as a drug carrier to investigate the loading and release properties of the Quercetin(QU).In this paper,mesoporous silica nanoparticles(MSN)were used as a substrate,and 3-aminopropyl triethyoxysilane was used as a surface modification agent to introduce—NH_(2),and the azobenzene-4,4’-dicarboxylic acid(AZO)was used as light responsive agent to introduce the group of—N=N—,and thenβ-cyclodextrin(β-CD)was combined with AZO through host-guest interaction to construct light responsive nanoparticles(MSN@β-CD).The structure and properties of the carrier were analyzed by FTIR,BET,XPS,TGA,XRD,SEM and TEM.In vitro drug release studies showed the release rate of QU@MSN@β-CD(dark)was 12.19%within 72 h,but the release rate of QU@MSN@β-CD(light 10 min)was 26.09%,exhibiting a light-responsive property.The CCK8 tests demonstrated that MSN@β-CD could significantly decrease the toxicity of QU.Therefore,the controllable light-responsive drug delivery system has great application prospects.
基金supported by National Natural Science Foundation of China(Grant No.82160430)Natural Science Foundation of Guangxi(Grant No.2020GXNSFAA159134 and 2019GXNSFAA185060)+1 种基金Guangxi Science and Technology Base and Talent Special Project(Grant No.GuikeAD19254003 and GuikeAD21075002)Nanning Qingxiu District Science and Technology Major Special Project(Grant No.2020013).
文摘Drug delivery via intra-articular(IA)injection has proved to be effective in osteoarthritis(OA)therapy,limited by the drug efficiency and short retention time of the drug delivery systems(DDSs).Herein,a series of modified cross-linked dextran(Sephadex,S0)was fabricated by respectively grafting with linear alkyl chains,branched alkyl chains or aromatic chain,and acted as DDSs after ibuprofen(Ibu)loading for OA therapy.This DDSs expressed sustained drug release,excellent anti-inflammatory and chondroprotective effects both in IL-1βinduced chondrocytes and OA joints.Specifically,the introduction of a longer hydrophobic chain,particularly an aromatic chain,distinctly improved the hydrophobicity of S0,increased Ibu loading efficiency,and further led to significantly improving OA therapeutic effects.Therefore,hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.
基金supported by the Program of the Scientific and Technological in Guiyang City(Grant No.Zhu Ke He[2020]-16-5)Program of Scientific and Technological Project in Guizhou Province(Grant No.[2020]4Y197,Qian Ke He Ji Chu ZK[2022]Yi Ban 516,Qian Ke He Ji Chu ZK[2021]Yi Ban 559)+3 种基金the Science and Technology Talents Growth Project in Education Department of Guizhou Province(Grant No.Qian Jiao He KY Zi[2021]4Y211)the Program of Science and Technology of Guizhou Provincial Health Commission(Grant No.gzwjkj2020-1-215)the Knowledge Innovation Special Project for Fundamental Research of Wuhan(Grant No.2022020801010461)the Sichuan Science and Technology Program(Grant No.2022NSFSC1420).
文摘Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and inflammation.Nevertheless,current therapeutic regimens are inadequate to promptly address the vast diversity of potential pathogens.Omiganan,an antimicrobial peptide,has shown promise for neutralizing endotoxins and eliminating diverse pathogens.However,its clinical application is hindered by safety and stability concerns.Herein,we present a nanoscale drug delivery system(Omi-hyd-Dex@HA NPs)that selectively targets infectious microenvironments(IMEs)and responds to specific stimuli for efficient intervention in sepsis.The system consists of omiganan-dexamethasone conjugates linked by hydrazone bonds which self-assemble into nanoparticles coated with a hyaluronic acid(HA).The HA coating not only facilitates IMEs-targeting through interaction with intercellular-adhesion-molecule-1 on inflamed endotheliocytes,but also improves the biosafety of the nanosystem and enhances drug accumulation in primary infection sites triggered by hyaluronidase.The nanoparticles release dual drugs in IMEs through pH-sensitive cleavage of hydrazone bonds to eradicate pathogens and suppress inflammation.In multiple tissue infection and sepsis animal models,Omi-hyd-Dex@HA NPs exhibited rapid source control and comprehensive inflammation reduction,thereby preventing subsequent fatal complications and significantly improving survival outcomes.The bio-responsive and self-delivering nanosystem offers a promising strategy for systemic sepsis treatment in emergencies.
文摘Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.
基金the financial support of Isfahan University of Medical Sciences by grant No.#199180.
文摘The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.
基金Hainan Innovation Team Project of Hainan(820CXTD448)Hainan Province Key R&D Program International Science and Technology Cooperation Project(GHYF2022011)+8 种基金Key R&D Projects in Hainan ProvincZDYF2020223Hainan Provincial Major Science and Technology Project(ZDKJ2021036)Hainan Provincial Natural Science Foundation of High-level Talent Project 2019RC212Chinese Academy of Medical Sciences Medical and Health Science and Technology Innovation Engineering Project(2019-12M-5-023)Major Science and Technology Project of Hainan Province(ZDKJ2021039,ZDKJ202004)Key Topics of Hainan Medical College's Educational and Scientific Research Projects(HYZD202111)National Natural Science Foundation of China(81860001,82011530049 and 82160012)Open Project of the Key Laboratory of Tropical Disease Prevention and Control of the NHC(2021NHCTDCKFKT21008)Hainan Provincial Clinical Medical Center Construction Project Fund。
文摘With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of respiratory diseases,clinical intervention is still mainly based on drug control of pulmonary symptoms.However,systemic drugs have disadvantages such as many adverse reactions and severe systemic side effects.In recent years,the research and development of local drug delivery systems for the respiratory tract has brought new changes to the treatment of respiratory diseases.Locally delivered drugs can directly act on the airways and have the characteristics of fast onset,good curative effect and small side effects.It is a simple,efficient and safe treatment method,which has a very significant effect,and has become a hot topic of current research and promotion.This paper briefly reviews the development track and latest research progress of respiratory local drug delivery systems at home and abroad,in order to provide reference for clinical workers in drug selection and application.
基金Supported by Science and Health Joint Medical Research Project of Chongqing,No.2022MSXM133Natural Science Foundation of Chongqing,No.CSTB2022NSCQ-MSX1522,No.CSTB2023NSCQ-MSX0246,No.CSTB2022NSCQ-MSX1271+1 种基金The First Batch of Key Disciplines on Public Health in Chongqing and ScienceHealth Joint Project of Dazu District Science and Technology Bureau,No.DZKJ,2022CCC1001.
文摘The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of life,but also imposes a substantial burden on the healthcare system.In spite of efforts made in clinical practice,treating DFU remains a challenging task.While mesenchymal stem cell(MSC)therapy has been extensively studied in treating DFU,the current efficacy of DFU healing using this method is still inadequate.However,in recent years,several MSCs-based drug delivery systems have emerged,which have shown to increase the efficacy of MSC therapy,especially in treating DFU.This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.
基金supported by the Scientific Research Project of Liaoning Province Education Department(2020LJC16)
文摘The number of people with eye diseases has increased with the use of electronics.However,the bioavailability of eye drops remains low owing to the presence of the ocular barrier and other reasons.Although many drug delivery systems have been developed to overcome these problems,they have certain limitations.In recent years,the development of contact lenses that can deliver drugs for long periods with high bioavailability and without affecting vision has increased the interest in using contact lenses for drug delivery.Hence,a review of the current state of research on drug delivery contact lenses has become crucial.This article reviews the key physical and chemical properties of drug-laden contact lenses,development and classification of contact lenses,and features of the commonly used materials.A review of the methods commonly used in current research to create contact lenses has also been presented.An overview on how drug-laden contact lenses can overcome the problems of high burst and short release duration has been discussed.Overall,the review focuses on drug delivery methods using smart contact lenses,and predicts the future direction of research on contact lenses.
基金Supported by National Natural Science Foundation of China,No.81891004Tianjin Natural Science Foundation of China,No.21JCQNJC01140.
文摘BACKGROUND Intractable postherpetic neuralgia(PHN)can be difficult to manage even with aggressive multimodal therapies.Patients who experience uncontrolled refractory cranial PHN despite conservative treatment may benefit from an intrathecal drug delivery system(IDDS).For craniofacial neuropathic pain,the traditional approach has been to place the intrathecal catheter tip below the level of the cranial nerve root entry zones,which may lead to insufficient analgesia.CASE SUMMARY We describe a 69-year-old man with a 1-year history of PHN after developing a vesicular rash in the ophthalmic division of cranial nerve V(trigeminal nerve)distribution.The pain was rated 7-8 at rest and 9-10 at breakthrough pain(BTP)on a numeric rating scale.Despite receiving aggressive multimodal therapies including large doses of oral analgesics(gabapentin 150 mg q12 h,oxycodone 5 mg/acetaminophen 325 mg q6 h,and lidocaine 5%patch 700 mg q12 h)and sphenopalatine ganglion block,there was no relief of pain.Subsequently,the patient elected to have an implantable IDDS with the catheter tip placed at the interpeduncular cistern.The frequency of BTP episodes decreased.The patient’s continuous daily dose was adjusted to 0.032 mg/d after 3 mo of follow-up and stopped 5 mo later.He did not report pain or other discomfort at outpatient follow-up 6 mo and 1 year after stopping intracisternal hydromorphone.CONCLUSION The use of interpeduncular cistern intrathecal infusion with low-dose hydromorphone by IDDS may be effective for severe craniofacial PHN.
基金funded by the Science and Technology Development Fund,Macao S.A.R(Grant No.0023/2019/A and SKLQRCM(UM)-2020-2022,China)National Key Research and Development Program of China(Grant No.2017YFE0191500)the Research Fund of the University of Macao,Macao S.A.R.(Grant No.MYRG2019-00143-ICMS,China)
文摘Inflammatory bowel disease(IBD)is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization.With no curative therapy for IBD at present,the development of effective therapeutics is highly advocated.Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention(EPR)effect caused by the inflammation.However,the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release.Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs,ligandmodified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects.This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands.Finally,challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.
基金supported by the National Natural Science Foundation of China(No.81173006)Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.JKGQ201107)+1 种基金the Jiangsu Natural Science Foundation of China(No.BK20131312)the 12th of Six Talent Peak Foundation of Jiangsu Province
文摘The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid(HGA) conjugate for intravenous paclitaxel(PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles(PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio(TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects.
