The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circum...The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results.In addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc delivery.This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain delivery.Based on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration.The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out.Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the brain.These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.展开更多
AIM: To design and investigate the efficacy of a modified nanostructured lipid carrier loaded with genistein(Gen-NLC) to inhibit human lens epithelial cells(HLECs) proliferation.·METHODS: Gen-NLC was made by melt...AIM: To design and investigate the efficacy of a modified nanostructured lipid carrier loaded with genistein(Gen-NLC) to inhibit human lens epithelial cells(HLECs) proliferation.·METHODS: Gen-NLC was made by melt emulsification method. The morphology, particle size(PS), zeta potentials(ZP), encapsulation efficiency(EE) and in vitro release were characterized. The inhibition effect of nanostructured lipid carrier(NLC), genistein(Gen) and Gen-NLC on HLECs proliferation was evaluated by cell counting kit-8(CCK-8) assay, gene and protein expression of the proliferation marker Ki67 were evaluated with real-time quantitative polymerase chain reaction(RT-q PCR) and immunofluorescence analyses.·RESULTS: The mean PS of Gen-NLC was 80.12±1.55 nm with a mean polydispersity index of 0.11±0.02. The mean ZP was-7.14 ±0.38 m V and the EE of Gen in the nanoparticles was 92.3% ±0.73%. Transmission electron microscopy showed that Gen-NLC displayed spherical-shaped particles covered by an outer-layer structure. In vitro release experiments demonstrated a prolonged drug release for 72 h. The CCK-8 assay results showed the NLC had no inhibitory effect on HLECs and Gen-NLC displayed a much more prominent inhibitory effect on cellular growth compared to Gen of the same concentration. The m RNA and protein expression of Ki67 in LECs decreased significantly in Gen-NLC group.·CONCLUSION: Sustained drug release by Gen-NLCs may impede HLEC growth.展开更多
The objective of this study was to prepare nanostructured lipid carrier(NLC)-based topical gel of Ganoderma Triterpenoids(GTs) and evaluate their effects on frostbite treatment. GT-NLCs was prepared by the high pressu...The objective of this study was to prepare nanostructured lipid carrier(NLC)-based topical gel of Ganoderma Triterpenoids(GTs) and evaluate their effects on frostbite treatment. GT-NLCs was prepared by the high pressure homogenization method and then characterized by morphology and analyses of particle size, zeta potential, entrapment efficiency(EE), and drug loading(DL). The NLCs was suitably gelled for skin permeation studies in vitro and pharmacodynamic evaluation in vivo, compared with the GT emulgel. The GT-NLC remained within the colloidal range and was uniformly dispersed after suitably gelled by carbopol preparation. Transmission electron microscopy(TEM) study showed GT-NLCs was spherical in shape. The EE(%) and DL(%) could reach up to(81.84 ± 0.60)% and(2.13 ± 0.12)%, respectively. The result of X-ray diffractograms(XRD) showed that GTs were in an amorphous state in the NLC-gel. In vitro permeation studies through rat skin indicated that the amount of GTs permeated through skin of GT-NLCs after 24 h was higher than that of GT emulsion, and GT-NLCs increased the accumulative amounts of GTs in epidermis 7.76 times greater than GT emulsion. GT-NLC-gel was found to possess superior therapeutic effect for frostbite, compared with the GT emulgel. The NLC based topical gel of GTs could improve-their therapeutic effect for frostbite.展开更多
基金supported by Fundacao para a Ciência e a Tecnologia(FCT)(SFRH/136177/2018,Portugal)the Applied Molecular Biosciences Unit-UCIBIO which is fnanced by national funds from FCT(UIDP/04378/2020 and UIDB/04378/2020)。
文摘The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results.In addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc delivery.This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain delivery.Based on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration.The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out.Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the brain.These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.
基金Supported by the National Natural Science Foundation for Distinguished Young Scholars of China (No. 81100654)
文摘AIM: To design and investigate the efficacy of a modified nanostructured lipid carrier loaded with genistein(Gen-NLC) to inhibit human lens epithelial cells(HLECs) proliferation.·METHODS: Gen-NLC was made by melt emulsification method. The morphology, particle size(PS), zeta potentials(ZP), encapsulation efficiency(EE) and in vitro release were characterized. The inhibition effect of nanostructured lipid carrier(NLC), genistein(Gen) and Gen-NLC on HLECs proliferation was evaluated by cell counting kit-8(CCK-8) assay, gene and protein expression of the proliferation marker Ki67 were evaluated with real-time quantitative polymerase chain reaction(RT-q PCR) and immunofluorescence analyses.·RESULTS: The mean PS of Gen-NLC was 80.12±1.55 nm with a mean polydispersity index of 0.11±0.02. The mean ZP was-7.14 ±0.38 m V and the EE of Gen in the nanoparticles was 92.3% ±0.73%. Transmission electron microscopy showed that Gen-NLC displayed spherical-shaped particles covered by an outer-layer structure. In vitro release experiments demonstrated a prolonged drug release for 72 h. The CCK-8 assay results showed the NLC had no inhibitory effect on HLECs and Gen-NLC displayed a much more prominent inhibitory effect on cellular growth compared to Gen of the same concentration. The m RNA and protein expression of Ki67 in LECs decreased significantly in Gen-NLC group.·CONCLUSION: Sustained drug release by Gen-NLCs may impede HLEC growth.
基金supported by Beijing Natural Science Foundation of China(No.7122176)National Natural Science Foundation of China(No.81102821)National Key New Drugs Innovation Foundation(Nos.2014ZX09J14106-01A and CWS11J165)
文摘The objective of this study was to prepare nanostructured lipid carrier(NLC)-based topical gel of Ganoderma Triterpenoids(GTs) and evaluate their effects on frostbite treatment. GT-NLCs was prepared by the high pressure homogenization method and then characterized by morphology and analyses of particle size, zeta potential, entrapment efficiency(EE), and drug loading(DL). The NLCs was suitably gelled for skin permeation studies in vitro and pharmacodynamic evaluation in vivo, compared with the GT emulgel. The GT-NLC remained within the colloidal range and was uniformly dispersed after suitably gelled by carbopol preparation. Transmission electron microscopy(TEM) study showed GT-NLCs was spherical in shape. The EE(%) and DL(%) could reach up to(81.84 ± 0.60)% and(2.13 ± 0.12)%, respectively. The result of X-ray diffractograms(XRD) showed that GTs were in an amorphous state in the NLC-gel. In vitro permeation studies through rat skin indicated that the amount of GTs permeated through skin of GT-NLCs after 24 h was higher than that of GT emulsion, and GT-NLCs increased the accumulative amounts of GTs in epidermis 7.76 times greater than GT emulsion. GT-NLC-gel was found to possess superior therapeutic effect for frostbite, compared with the GT emulgel. The NLC based topical gel of GTs could improve-their therapeutic effect for frostbite.
