The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) ...The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.展开更多
In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles(MSNs) with a functio...In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles(MSNs) with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanoparticles, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.展开更多
Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro-and nano-scale.On the nanoscale,they are potential novel smart materials for drug delivery systems that could combine the ...Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro-and nano-scale.On the nanoscale,they are potential novel smart materials for drug delivery systems that could combine the relative strengths of liposome and polymersome drug delivery systems without their respective weaknesses.However,little is known about their properties and how they could be tailored.Currently,most methods of investigation are limited to the microscale.Here we provide a brief review on hybrid vesicle systems with a specific focus on recent developments demonstrating that nanoscale hybrid vesicles have different properties from their macroscale counterparts.展开更多
Parenteral sustained release drug formulations, acting as preferable platforms for longterm exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypode...Parenteral sustained release drug formulations, acting as preferable platforms for longterm exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypodermic injection. Therefore, issues including needle-phobic, needle-stick injuries and inappropriate reuse of needles would hamper the further applications of these delivery platforms. Microneedles (MNs) as a potential alternative system for hypodermic needles can benefit from minimally invasive and self-administration. Recently, polymeric microneedle-mediated sustained release systems (MN@SRS) have opened up a new way for treatment of many diseases. Here, we reviewed the recent researches in MN@SRS for transdermal delivery, and summed up its typical design strategies and applications in various diseases therapy, particularly focusing on the applications in contraception, infection, cancer, diabetes, and subcutaneous disease. An overview of the present clinical translation difficulties and future outlook of MN@SRS was also provided.展开更多
Glaucoma,a leading cause of irreversible blindness,affects more than 64 million people worldwide and is expected to grow in number due to the aging global population and enhanced methods of detection.Although topical ...Glaucoma,a leading cause of irreversible blindness,affects more than 64 million people worldwide and is expected to grow in number due to the aging global population and enhanced methods of detection.Although topical therapies are often effective when used as prescribed,the drawbacks of current medical management methods include poor patient adherence,local and systemic side effects,and in some cases,limited therapeutic efficacy.Novel ocular drug delivery platforms promise to deliver differentiated drug formulations with targeted delivery leveraging patient-independent administration.Several platforms are in various stages of development with promising pre-clinical and clinical data.The Bimatoprost Sustained Release (SR) intracameral implant was approved in the United States in March of 2020,making it the first long-term injectable therapy available for the treatment of glaucoma.This review aims to provide an update on novel sustained release drug delivery systems that are available today as well as those that might be commercialized in coming years.展开更多
In this paper, it was investigated that the effect of parameters such as the ionic strength, pH, counter-ion type of release medium, particle size, and cross linkage of cation exchange resin on the release of model dr...In this paper, it was investigated that the effect of parameters such as the ionic strength, pH, counter-ion type of release medium, particle size, and cross linkage of cation exchange resin on the release of model drug pseudoephedrine hydrochloride (PE) from uncoated drug-resin complex. The drug-resin complex was prepared by the reaction of PE with strongly acidic cation exchange resin (001×4, 001×7, 001×14). The result showed that the loading of PE increased with the increase of temperatures. The release of PE from drug-resin complex at 37℃ was monitored in vitro. From the experiments, it was found that the release rate of PE depends on the pH, composition of the releasing media, increased at lower pH media or with increase of ionic strength of media. Moreover, the release rate of PE was inversely proportional to the cross-linkage and particle size of the cation exchange resin.展开更多
Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we...Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.展开更多
The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosy...The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosystem, liposomes naturally come under the spotlight of this trend. This review summarizes the latest development about the design and construction of photo-responsive liposomes with gold nanoparticles for the controlled drug release. Alongside, we overview the mechanism involved in this process and the representative applications.展开更多
In the present study,we prepared nattokinase-loaded self-double-emulsifying drug delivery system(SDEDDS)and investigated its preliminary pharmacodynamics.The type and concentration of oil phase,inner aqueous phase and...In the present study,we prepared nattokinase-loaded self-double-emulsifying drug delivery system(SDEDDS)and investigated its preliminary pharmacodynamics.The type and concentration of oil phase,inner aqueous phase and emulsifier were screened to prepare optimum nattokinase-loaded SDEDDS.Next,the optimum formulations were characterized based on microstructure,volume-weighted mean droplet size,self-emulsifying rate,yield,storage stability,in vitro release and in vivo pharmacodynamics studies.The water/oil/watermultiple emulsions exhibited typicalmultiple structure,with relatively small volumeweighted mean droplet size 6.0±0.7μm and high self-emulsifying ability(self-emulsifying time<2 min).Encapsulation of nattokinase was up to 86.8±8.2%.The cumulative release of nattokinase within 8 h was about 30%,exhibiting a sustained release effect.The pharmacodynamics study indicated that nattokinase-loaded SDEDDS could significantly prolong the whole blood clotting time in mouse and effectively improve the carrageenan-induced tail thrombosis compared with nattokinase solution.Moreover,we showed that SDEDDS could successfully self-emulsify into water/oil/water multiple emulsions upon dilution in dispersion medium with gentle stirring and effectively protect nattokinase activity in gastric environment.Our findings suggested that SDEDDS could be a promising strategy for peptide and protein drugs by oral administration.展开更多
Hybrid drug delivery systems(DDS) have been prepared by grafting poly(NIPAM-co-MPS) chains on multimodal porous silica nanoparticles having an inner mesoporous structure and an outer thin layer of micropores. The hybr...Hybrid drug delivery systems(DDS) have been prepared by grafting poly(NIPAM-co-MPS) chains on multimodal porous silica nanoparticles having an inner mesoporous structure and an outer thin layer of micropores. The hybrid thermoresponsive DDS were fully characterized and loaded with a model drug. The in vitro drug release tests are carried out at below and above the lower critical solution temperature(LCST) of the copolymer. The results have revealed that due to the presence of small diameter(~1.3 nm) micropores at the periphery of the particles, the collapsed globules of the thermoresponsive copolymer above its LCST hinders the complete release of the drug which resulted in a reverse thermoresponsive drug release profile by the hybrid DDS.展开更多
Electrospinning is a very simple and versatile process by which polymer nanofibers with di-ameters ranging from a few nanometers to sev-eral micrometers can be produced using an electrostatically driven jet of polymer...Electrospinning is a very simple and versatile process by which polymer nanofibers with di-ameters ranging from a few nanometers to sev-eral micrometers can be produced using an electrostatically driven jet of polymer solution or polymer melt. Significant progress has been made in this process throughout the past few years and electrospinning has advanced its ap-plications in many fields, including pharmaceu-tics. Electrospun nanofibers show great prom-ise for developing many types of novel drug delivery systems (DDS) due to their special characteristics and the simple but useful and effective top-down fabricating process. The current state of electrospun nanofiber-based DDS is focused on drug-loaded nanofiber preparation from pharmaceutical and biode-gradable polymers and different types of DDS. However, there are more opportunities to be exploited from the electrospinning process and the corresponding drug-loaded nanofibers for drug delivery. Additionally, some other related challenges and the possible resolutions are outlined in this review.展开更多
Conventional tumor-targeted drug delivery systems(DDSs)face challenges,such as unsatisfied systemic circulation,low targeting efficiency,poor tumoral penetration,and uncontrolled drug release.Recently,tumor cellular m...Conventional tumor-targeted drug delivery systems(DDSs)face challenges,such as unsatisfied systemic circulation,low targeting efficiency,poor tumoral penetration,and uncontrolled drug release.Recently,tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas.With the introduction of several additional functionalities,the properties of these smart DDSs including size,surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting,and eventually achieve desired drug release for an optimized therapeutic efficiency.This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery.Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli,including pH,glutathione,adenosine-triphosphate,reactive oxygen species,enzyme and inflammatory factors are summarized.Special emphasis of this review is placed on their responsive mechanisms,drug loading models,drawbacks and merits.Several typical multi-stimuli responsive DDSs are listed.And the main challenges and potential future development are discussed.展开更多
An oil-in-water (O/W) solvent evaporation method was used to prepare biodegradable microspheresbased on poly(D,L-lactic acid) (PLA). Nifedipine, a hydrophobic drug, was chosen as a model molecule in the studyof drug e...An oil-in-water (O/W) solvent evaporation method was used to prepare biodegradable microspheresbased on poly(D,L-lactic acid) (PLA). Nifedipine, a hydrophobic drug, was chosen as a model molecule in the studyof drug entrapment and release. Effect of preparation conditions on the size, morphology, drug loading, and releaseprofiles of micropheres was investigated. Based on in vitro release experimental findings, a diffusion/dissolutionmodel was presented for quantitative description of the resulting release behaviors and drug release kinetics fromPLA microspheres analyzed. The mathematical models were used to predict the effect of microstructure on theresulting drug release. It provided an approach to determine the suitable structure parameters for microspheres toachieve desired drug release behaviors.展开更多
This review provides a glimpse of the potential of the biodegradable phos-phoryl-containing polymers in medical applications. Undoubtedly these polymerspossess unique properties that are yet to be fully understood. Ma...This review provides a glimpse of the potential of the biodegradable phos-phoryl-containing polymers in medical applications. Undoubtedly these polymerspossess unique properties that are yet to be fully understood. Many areas warrantfurther investigation and much optimization remains to be done. The fascinatingchemistry of phosphorus poses interesting hurdles but at the same time leavesample room for polymer scientists to exercise their creativity in designinginteresting biomaterials. As the mutual understanding between basic and clinicalscientists on the need of medical devices and the capabilities of these newbiomaterials expands, imaginative application of new biomaterials to other medi-cal applications can be expected.展开更多
The intention behind the present work was to develop a microsponge based novel dosage form for sustained delivery of domperidone.Quasi-emulsion solvent diffusion method was employed using Eudragit RS-100 with various ...The intention behind the present work was to develop a microsponge based novel dosage form for sustained delivery of domperidone.Quasi-emulsion solvent diffusion method was employed using Eudragit RS-100 with various drug-polymer ratios for the preparation of microsponges.For optimization purposes,several factors which affect microparticles’physical properties were investigated.Characterization techniques followed for the formed microsponges were DSC,FTIR,SEM,XRD and particle size analysis,along with morphology,drug loading and in vitro drug release.It was found that there were no chemical interactions between drugs and polymers used as per DSC and FTIR results.The drug-polymer ratio showed remarkable impact on drug content,encapsulation efficiency and particle size.SEM micrographs revealed that microsponges were spherical in shape with porous surface,and had 104±0.22μm mean particle size.The microsponges were then loaded in capsules followed by in vitro drug release study;which depicted that microsponges with drug-polymer ratio of 1:2 were more proficient to give extended drug release of 76.38%at the end of 8 h,superior in contrast to conventional marketed formulation Domstal®,which got exhausted incredibly earlier by releasing 82.57%drug at the end of 1⁄2 h only.Hence,the developed microsponge based formulation of domperidone would be an expectant,promising substitute to conventional therapy of gastroparesis,emesis and alike gastric ailments.展开更多
The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution an...The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution and design a sustained release system.MWNTs were modified with a carboxyl group by acid treatment and then complex with PAMAM.PAMAM-MWNTs were investigated as a scaffold for loading the model drug,Carvedilol(CAR),using three different methods(the fusion method,the incipient wetness impregnation method,and the solvent method).The effects of different pore size,specific surface area and physical state were systematically studied using FT-IR,TGA,SEM,DSC,nitrogen adsorption,XPS and XRD.All the samples made by PAMAM-MWNTs to load the drug had a marked effect on the drug-loading capacity as well as drug dissolution,especially theⅡ-30%.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
We have developed a controlled-release drug carrier. Smartly controlled-release polymer nanoparticles were firstly synthesized through RAFT polymerization as the controlled-release core. The structural and particle pr...We have developed a controlled-release drug carrier. Smartly controlled-release polymer nanoparticles were firstly synthesized through RAFT polymerization as the controlled-release core. The structural and particle properties of polymer nanoparticles were characterized by nuclear magnetic resonance spectroscopy (1H-NMR), scanning electron microscope (SEM) and X-ray spectroscopy (EDX). Mesoporous materials were selected as the shell materials to encapsulate the smart core as the stable shell. The mesoporous shell was characterized by transmission electron microscopy (TEM) and scanning electron microscope (SEM). All the results showed that a well-defined core-shell structure with mesoporous structure was obtained, and this controllable delivery system will have the great potential in nanomedicine.展开更多
Personalized drugs,as well as disease-specific and condition-dependent drug release,have been highly desired in drug delivery systems for effective and safe therapies.Four-dimensional(4 D)printing,as a newly emerging ...Personalized drugs,as well as disease-specific and condition-dependent drug release,have been highly desired in drug delivery systems for effective and safe therapies.Four-dimensional(4 D)printing,as a newly emerging technique to develop drug capsules,displays unique advantages that can autonomously control drug release according to the actual physiological circumstances.Herein,core-shell structured hydrogel capsules were developed using a multimaterial extrusion-based 4 D printing method,which consists of a model drug as the core and UV cross-linked poly(N-isopropylacrylamide)(PNIPAM)hydrogel as the shell.Owing to the lower critical solution temperature(LCST)-induced shrinking/swelling properties,the prepared PNIPAM hydrogel capsules showed temperature-responsive drug release along with the topography changes in the cross-linked PNIPAM network.The in vitro drug release test confirmed that the PNIPAM hydrogel capsules can autonomously control their drug release behaviors according to changes in ambient temperature.Moreover,the increased shell thickness of these capsules causes an obvious reduction in drug release rate,distinctly indicating that the drug release behavior can be well adjusted by setting the shell thickness of the capsules.The proposed 4 D printing strategy pioneers the paradigm of smart drug release by showing great potential in the smart controlled release of drugs and macromolecular active agents.展开更多
The term Diabetes Mellitus (DM) comprises a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in the secretion and/or action of insulin. The Insulin therapy constitutes the pre...The term Diabetes Mellitus (DM) comprises a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in the secretion and/or action of insulin. The Insulin therapy constitutes the preferred treatment for DM, consisting of daily subcutaneous insulin injections to control blood glucose levels. The chitosan studied for Biomedicine is a biomaterial that can be used for controlled release of drugs whose release rate can be controlled by Sodium Tripolyphosphate (TPP), which is an ionic cross linker of the chitosan. Present study, therefore, was aimed to develop and evaluate membranes of chitosan and chitosan cross linked by TPP for use in controlled release of insulin system, with the purpose of obtaining an alternative to the injectable administration of this drug. The developed membranes were characterized by the techniques of Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), High Performance Liquid Chromatography (HPLC) and Evaluation of Cell Viability of Macrophages (MTT). With the FTIR technique the interaction between chitosan, tripolyphosphate and insulin was identified. Chemical elements present in chitosan, insulin and sodium tripolyphosphate membranes were detected by EDX technique. By SEM technique, the changes in the morphology of the membrane containing insulin, with the presence of granular particles of varying sizes, could be observed when compared to pure chitosan. With HPLC assay insulin was identified and it was shown that it gets separated from chitosan membrane even when the membrane was cross linked by the TPP, though at a reduced rate. The crosslinking agent was effective to control the rate of insulin release. The biocompatibility of the prepared membranes was confirmed by cell viability of macrophages using the MTT assay. The developed membranes, therefore, have potential for use as a biomaterial in controlled release systems for insulin.展开更多
基金supported by the National Natural Science Foundation of China(81771006)。
文摘The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.
基金supported by the Chinese Natural Science Foundation Project (Grant No. 30970784 and 81171455)a National Distinguished Young Scholars Grant (Grant No. 31225009) from the National Natural Science Foundation of China+5 种基金the National Key Basic Research Program of China (Grant No. 2009CB930200)the Chinese Academy of Sciences (CAS) ‘Hundred Talents Program’ (Grant No. 07165111ZX)the CAS Knowledge Innovation Program, and the State HighTech Development Plan (Grant No. 2012AA020804)the ‘Strategic Priority Research Program’ of the Chinese Academy of Sciences (Grant No. XDA09030301)NIH/NIMHD 8 G12 MD007597USAMRMC W81XWH-10-1-0767 grants
文摘In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles(MSNs) with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanoparticles, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.
基金the work from the European Research Council under the European Union's Seventh Framework Program(FP/2007-2013)/ERC grant agreement No.310034the Austrian Science Fund(FWF)grant No.I 3064.
文摘Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro-and nano-scale.On the nanoscale,they are potential novel smart materials for drug delivery systems that could combine the relative strengths of liposome and polymersome drug delivery systems without their respective weaknesses.However,little is known about their properties and how they could be tailored.Currently,most methods of investigation are limited to the microscale.Here we provide a brief review on hybrid vesicle systems with a specific focus on recent developments demonstrating that nanoscale hybrid vesicles have different properties from their macroscale counterparts.
基金financial support from the National Natural Science Foundation of China (32071342 and 31922042)Guangdong Special Support Program (2019TQ05Y209)the Fundamental Research Funds for the Central Universities (19ykzd31)。
文摘Parenteral sustained release drug formulations, acting as preferable platforms for longterm exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypodermic injection. Therefore, issues including needle-phobic, needle-stick injuries and inappropriate reuse of needles would hamper the further applications of these delivery platforms. Microneedles (MNs) as a potential alternative system for hypodermic needles can benefit from minimally invasive and self-administration. Recently, polymeric microneedle-mediated sustained release systems (MN@SRS) have opened up a new way for treatment of many diseases. Here, we reviewed the recent researches in MN@SRS for transdermal delivery, and summed up its typical design strategies and applications in various diseases therapy, particularly focusing on the applications in contraception, infection, cancer, diabetes, and subcutaneous disease. An overview of the present clinical translation difficulties and future outlook of MN@SRS was also provided.
文摘Glaucoma,a leading cause of irreversible blindness,affects more than 64 million people worldwide and is expected to grow in number due to the aging global population and enhanced methods of detection.Although topical therapies are often effective when used as prescribed,the drawbacks of current medical management methods include poor patient adherence,local and systemic side effects,and in some cases,limited therapeutic efficacy.Novel ocular drug delivery platforms promise to deliver differentiated drug formulations with targeted delivery leveraging patient-independent administration.Several platforms are in various stages of development with promising pre-clinical and clinical data.The Bimatoprost Sustained Release (SR) intracameral implant was approved in the United States in March of 2020,making it the first long-term injectable therapy available for the treatment of glaucoma.This review aims to provide an update on novel sustained release drug delivery systems that are available today as well as those that might be commercialized in coming years.
文摘In this paper, it was investigated that the effect of parameters such as the ionic strength, pH, counter-ion type of release medium, particle size, and cross linkage of cation exchange resin on the release of model drug pseudoephedrine hydrochloride (PE) from uncoated drug-resin complex. The drug-resin complex was prepared by the reaction of PE with strongly acidic cation exchange resin (001×4, 001×7, 001×14). The result showed that the loading of PE increased with the increase of temperatures. The release of PE from drug-resin complex at 37℃ was monitored in vitro. From the experiments, it was found that the release rate of PE depends on the pH, composition of the releasing media, increased at lower pH media or with increase of ionic strength of media. Moreover, the release rate of PE was inversely proportional to the cross-linkage and particle size of the cation exchange resin.
基金The authors gratefully acknowledge financial support from National Natural Science Foundation of China(81872818)National Key R&D Program of China(2021YFE0115200).
文摘Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.
文摘The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosystem, liposomes naturally come under the spotlight of this trend. This review summarizes the latest development about the design and construction of photo-responsive liposomes with gold nanoparticles for the controlled drug release. Alongside, we overview the mechanism involved in this process and the representative applications.
基金supported by National Natural Science Foundation of China(No.81373338).
文摘In the present study,we prepared nattokinase-loaded self-double-emulsifying drug delivery system(SDEDDS)and investigated its preliminary pharmacodynamics.The type and concentration of oil phase,inner aqueous phase and emulsifier were screened to prepare optimum nattokinase-loaded SDEDDS.Next,the optimum formulations were characterized based on microstructure,volume-weighted mean droplet size,self-emulsifying rate,yield,storage stability,in vitro release and in vivo pharmacodynamics studies.The water/oil/watermultiple emulsions exhibited typicalmultiple structure,with relatively small volumeweighted mean droplet size 6.0±0.7μm and high self-emulsifying ability(self-emulsifying time<2 min).Encapsulation of nattokinase was up to 86.8±8.2%.The cumulative release of nattokinase within 8 h was about 30%,exhibiting a sustained release effect.The pharmacodynamics study indicated that nattokinase-loaded SDEDDS could significantly prolong the whole blood clotting time in mouse and effectively improve the carrageenan-induced tail thrombosis compared with nattokinase solution.Moreover,we showed that SDEDDS could successfully self-emulsify into water/oil/water multiple emulsions upon dilution in dispersion medium with gentle stirring and effectively protect nattokinase activity in gastric environment.Our findings suggested that SDEDDS could be a promising strategy for peptide and protein drugs by oral administration.
文摘Hybrid drug delivery systems(DDS) have been prepared by grafting poly(NIPAM-co-MPS) chains on multimodal porous silica nanoparticles having an inner mesoporous structure and an outer thin layer of micropores. The hybrid thermoresponsive DDS were fully characterized and loaded with a model drug. The in vitro drug release tests are carried out at below and above the lower critical solution temperature(LCST) of the copolymer. The results have revealed that due to the presence of small diameter(~1.3 nm) micropores at the periphery of the particles, the collapsed globules of the thermoresponsive copolymer above its LCST hinders the complete release of the drug which resulted in a reverse thermoresponsive drug release profile by the hybrid DDS.
文摘Electrospinning is a very simple and versatile process by which polymer nanofibers with di-ameters ranging from a few nanometers to sev-eral micrometers can be produced using an electrostatically driven jet of polymer solution or polymer melt. Significant progress has been made in this process throughout the past few years and electrospinning has advanced its ap-plications in many fields, including pharmaceu-tics. Electrospun nanofibers show great prom-ise for developing many types of novel drug delivery systems (DDS) due to their special characteristics and the simple but useful and effective top-down fabricating process. The current state of electrospun nanofiber-based DDS is focused on drug-loaded nanofiber preparation from pharmaceutical and biode-gradable polymers and different types of DDS. However, there are more opportunities to be exploited from the electrospinning process and the corresponding drug-loaded nanofibers for drug delivery. Additionally, some other related challenges and the possible resolutions are outlined in this review.
基金Supported by the Huxiang Young Talent Program of Hunan Province(2018RS3005)The Project of Innovation-driven Plan in Central South University(2020CX048)+3 种基金Hunan Provincial Natural Science Foundation of China(2019JJ60071,2020JJ4680)the Shenghua Yuying Project of Central South University,the Hunan Provincial Postgraduate Research and Innovation Project(CX20190242)Postgraduate Independent Exploration and Innovation Project of Central South University(2019zzts1017,2019zzts750)the Key Research Fund of Hunan Provincial Education Department(18A211).
文摘Conventional tumor-targeted drug delivery systems(DDSs)face challenges,such as unsatisfied systemic circulation,low targeting efficiency,poor tumoral penetration,and uncontrolled drug release.Recently,tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas.With the introduction of several additional functionalities,the properties of these smart DDSs including size,surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting,and eventually achieve desired drug release for an optimized therapeutic efficiency.This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery.Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli,including pH,glutathione,adenosine-triphosphate,reactive oxygen species,enzyme and inflammatory factors are summarized.Special emphasis of this review is placed on their responsive mechanisms,drug loading models,drawbacks and merits.Several typical multi-stimuli responsive DDSs are listed.And the main challenges and potential future development are discussed.
文摘An oil-in-water (O/W) solvent evaporation method was used to prepare biodegradable microspheresbased on poly(D,L-lactic acid) (PLA). Nifedipine, a hydrophobic drug, was chosen as a model molecule in the studyof drug entrapment and release. Effect of preparation conditions on the size, morphology, drug loading, and releaseprofiles of micropheres was investigated. Based on in vitro release experimental findings, a diffusion/dissolutionmodel was presented for quantitative description of the resulting release behaviors and drug release kinetics fromPLA microspheres analyzed. The mathematical models were used to predict the effect of microstructure on theresulting drug release. It provided an approach to determine the suitable structure parameters for microspheres toachieve desired drug release behaviors.
文摘This review provides a glimpse of the potential of the biodegradable phos-phoryl-containing polymers in medical applications. Undoubtedly these polymerspossess unique properties that are yet to be fully understood. Many areas warrantfurther investigation and much optimization remains to be done. The fascinatingchemistry of phosphorus poses interesting hurdles but at the same time leavesample room for polymer scientists to exercise their creativity in designinginteresting biomaterials. As the mutual understanding between basic and clinicalscientists on the need of medical devices and the capabilities of these newbiomaterials expands, imaginative application of new biomaterials to other medi-cal applications can be expected.
文摘The intention behind the present work was to develop a microsponge based novel dosage form for sustained delivery of domperidone.Quasi-emulsion solvent diffusion method was employed using Eudragit RS-100 with various drug-polymer ratios for the preparation of microsponges.For optimization purposes,several factors which affect microparticles’physical properties were investigated.Characterization techniques followed for the formed microsponges were DSC,FTIR,SEM,XRD and particle size analysis,along with morphology,drug loading and in vitro drug release.It was found that there were no chemical interactions between drugs and polymers used as per DSC and FTIR results.The drug-polymer ratio showed remarkable impact on drug content,encapsulation efficiency and particle size.SEM micrographs revealed that microsponges were spherical in shape with porous surface,and had 104±0.22μm mean particle size.The microsponges were then loaded in capsules followed by in vitro drug release study;which depicted that microsponges with drug-polymer ratio of 1:2 were more proficient to give extended drug release of 76.38%at the end of 8 h,superior in contrast to conventional marketed formulation Domstal®,which got exhausted incredibly earlier by releasing 82.57%drug at the end of 1⁄2 h only.Hence,the developed microsponge based formulation of domperidone would be an expectant,promising substitute to conventional therapy of gastroparesis,emesis and alike gastric ailments.
基金the National Basic Research Program of China(973 Program)(No.2009CB930300)National Natural Science Foundation of China(No.81273449).
文摘The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution and design a sustained release system.MWNTs were modified with a carboxyl group by acid treatment and then complex with PAMAM.PAMAM-MWNTs were investigated as a scaffold for loading the model drug,Carvedilol(CAR),using three different methods(the fusion method,the incipient wetness impregnation method,and the solvent method).The effects of different pore size,specific surface area and physical state were systematically studied using FT-IR,TGA,SEM,DSC,nitrogen adsorption,XPS and XRD.All the samples made by PAMAM-MWNTs to load the drug had a marked effect on the drug-loading capacity as well as drug dissolution,especially theⅡ-30%.
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Funded by National Natural Science Foundation of China (Nos.51861135313,U1663225,U1662134,21711530705,21673282,21473246)Fundamental Research Funds for the Central Universities (Nos.19lgpy112,19lgzd16,2019IB005)+3 种基金National Key R&D Program of China (No.2017YFC1103800)Program for Changjiang Scholars and Innovative Research Team in University (No.IRT_15R52)International Science&Technology Cooperation Program of China (No.2015DFE52870)Jilin Province Science and Technology Development Plan (No.20180101208JC)
文摘We have developed a controlled-release drug carrier. Smartly controlled-release polymer nanoparticles were firstly synthesized through RAFT polymerization as the controlled-release core. The structural and particle properties of polymer nanoparticles were characterized by nuclear magnetic resonance spectroscopy (1H-NMR), scanning electron microscope (SEM) and X-ray spectroscopy (EDX). Mesoporous materials were selected as the shell materials to encapsulate the smart core as the stable shell. The mesoporous shell was characterized by transmission electron microscopy (TEM) and scanning electron microscope (SEM). All the results showed that a well-defined core-shell structure with mesoporous structure was obtained, and this controllable delivery system will have the great potential in nanomedicine.
基金supported by the National Key R&D Program of China(No.2018YFB1105100)。
文摘Personalized drugs,as well as disease-specific and condition-dependent drug release,have been highly desired in drug delivery systems for effective and safe therapies.Four-dimensional(4 D)printing,as a newly emerging technique to develop drug capsules,displays unique advantages that can autonomously control drug release according to the actual physiological circumstances.Herein,core-shell structured hydrogel capsules were developed using a multimaterial extrusion-based 4 D printing method,which consists of a model drug as the core and UV cross-linked poly(N-isopropylacrylamide)(PNIPAM)hydrogel as the shell.Owing to the lower critical solution temperature(LCST)-induced shrinking/swelling properties,the prepared PNIPAM hydrogel capsules showed temperature-responsive drug release along with the topography changes in the cross-linked PNIPAM network.The in vitro drug release test confirmed that the PNIPAM hydrogel capsules can autonomously control their drug release behaviors according to changes in ambient temperature.Moreover,the increased shell thickness of these capsules causes an obvious reduction in drug release rate,distinctly indicating that the drug release behavior can be well adjusted by setting the shell thickness of the capsules.The proposed 4 D printing strategy pioneers the paradigm of smart drug release by showing great potential in the smart controlled release of drugs and macromolecular active agents.
文摘The term Diabetes Mellitus (DM) comprises a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in the secretion and/or action of insulin. The Insulin therapy constitutes the preferred treatment for DM, consisting of daily subcutaneous insulin injections to control blood glucose levels. The chitosan studied for Biomedicine is a biomaterial that can be used for controlled release of drugs whose release rate can be controlled by Sodium Tripolyphosphate (TPP), which is an ionic cross linker of the chitosan. Present study, therefore, was aimed to develop and evaluate membranes of chitosan and chitosan cross linked by TPP for use in controlled release of insulin system, with the purpose of obtaining an alternative to the injectable administration of this drug. The developed membranes were characterized by the techniques of Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), High Performance Liquid Chromatography (HPLC) and Evaluation of Cell Viability of Macrophages (MTT). With the FTIR technique the interaction between chitosan, tripolyphosphate and insulin was identified. Chemical elements present in chitosan, insulin and sodium tripolyphosphate membranes were detected by EDX technique. By SEM technique, the changes in the morphology of the membrane containing insulin, with the presence of granular particles of varying sizes, could be observed when compared to pure chitosan. With HPLC assay insulin was identified and it was shown that it gets separated from chitosan membrane even when the membrane was cross linked by the TPP, though at a reduced rate. The crosslinking agent was effective to control the rate of insulin release. The biocompatibility of the prepared membranes was confirmed by cell viability of macrophages using the MTT assay. The developed membranes, therefore, have potential for use as a biomaterial in controlled release systems for insulin.
