The purpose of this work was to explore the feasibility of ethosomes for improving the anti-arthritic efficacy of topically administered tetrandrine, a bisbenzylisoquinoline alkaloid. Ethosomes were prepared by using ...The purpose of this work was to explore the feasibility of ethosomes for improving the anti-arthritic efficacy of topically administered tetrandrine, a bisbenzylisoquinoline alkaloid. Ethosomes were prepared by using the transmembrane pH-gradient loading method and characterized by mean diameter, morphology and entrapment efficiency. The prepared tetrandrine-loaded ethosomes exhibited spherical shape with about 78 nm of average diameter and entrapment efficiency of （52.87±3.81）%, whereas the liposomes had bigger size （99 nm） and higher entrapment efficiency （98.80±0.01）%. In addition, ethosomes exhibited favorable and enhanced penetration behavior as compared with liposomes. More importantly, tetrandrine-loaded ethosomes had a significantly better anti-adjuvant arthritis efficacy in rats compared to liposomes formulation, but no significant difference in the anti-arthritic efficacy between tetrandrine-loaded ethosomes and commercial dexamethasone ointment was observed. These results suggest that ethosomes would be a promising nanocarrier for topical delivery of tetrandrine across skin.展开更多
One key of constructing ideal transdermal drug delivery system(TDDS)is enhancing the percutaneous rate of drugs without sacrificing compatibility.Ethosomes(Eths)have excellent transdermal performance as well as good b...One key of constructing ideal transdermal drug delivery system(TDDS)is enhancing the percutaneous rate of drugs without sacrificing compatibility.Ethosomes(Eths)have excellent transdermal performance as well as good biocompatibility,and thus been widely used as drug carrier.Hydrogel has good 3-dimensional mesh structure which is convenience for drugs release and storage.In this study,Eths were introduced into silk fibroin(SF)/polyvinyl alcohol(PVA)composite hydrogel to construct a novel TDDS through a green process.The Ethsomes(Eths)-SF/PVA composite hydrogel TDDS showed good mechanical properties(stress:(0.236±0.032)MPa;strain:(65.74±2.45)%).Also,skin fibroblasts can grow and proliferate well on this TDDS,indicating that this material has a good cytocompatibility.Furthermore,with doxorubicin hydrochloride(Dox)as a model drug loaded in ethosomes,in vitro studies showed that this TDDS was able to transdermally release Dox efficiently.Our data suggested this novel system had a good potential for application in TDD,though further evaluative study still needed to carry out.展开更多
Ethosomes are permeation-enhancing carriers, which significantly promote drug delivery into skin. Thus,the introduction of ethosomes into electrospun nanofibers may result in good effect on transdermal drug delivery. ...Ethosomes are permeation-enhancing carriers, which significantly promote drug delivery into skin. Thus,the introduction of ethosomes into electrospun nanofibers may result in good effect on transdermal drug delivery. In this work,a novel ethosome-loaded silk fibroin( SF) /polyethylene oxide( PEO) composite nanofiber was fabricated based on a green electrospinning process. The ethosome-loaded SF /PEO nanofiber was round and smooth as shown by scanning electron microscopy( SEM),and the incorporation of ethosome didn't significantly affect the morphology of the electrospun SF /PEO nanofiber. The data of Fourier transform infrares(FTIR)spectra suggested the existence of ethosome on the SF /PEO nanofiber and the transmission electron microscopy(TEM) clearly showed the distribution of ethosome on the ethosome-loaded SF nanofibers. This ethosome-loaded SF nanofibrous mat may have a promising application in transdermal drug delivery systems.展开更多
The aim of the present study is the formulation of mefenamic acid ethosomal gel by hot and cold methods.To prepare the mefenamic acid transdermal gel,ethosomes was selected as colloidal carriers.Ethosomes were prepare...The aim of the present study is the formulation of mefenamic acid ethosomal gel by hot and cold methods.To prepare the mefenamic acid transdermal gel,ethosomes was selected as colloidal carriers.Ethosomes were prepared by cold and hot methods.The obtained ethosomes were characterized with vesicular diameter,zeta potential,drug content,entrapment efficiency and in-vitro diffusion studies.The five formulations of ethosomes prepared by cold and hot methods were compared.Among the 10 formulations of ethosomes,E5 was considered as the best formulation because of its mean vesicular diameter of 854 nm,zeta potential of 20 mV,drug content of 96.3%,entrapment efficiency of 94.4%,sustained drug release for 12 hr,i.e.94.4.Then the E5 formulations was incorporated into gel.A comparative study was made between the plain gel and the ethosomal gel.The Ethosomal gel was considered the best because of its highest drug content spreadability,pH(6.9)and the sustained drug release profile for 12 hr.By comparison,the cold method shows better results.展开更多
Recent studies have suggested that the anti-tumour effect of the programmed cell death protein 1 monoclonal antibody(aPD-1)depends on the expression of interleukin-12(IL-12)by dendritic cells(DCs).Since DCs are abunda...Recent studies have suggested that the anti-tumour effect of the programmed cell death protein 1 monoclonal antibody(aPD-1)depends on the expression of interleukin-12(IL-12)by dendritic cells(DCs).Since DCs are abundant in skin tissues,transdermal delivery of IL-12 targeting DCs may significantly improve the anti-tumour effect of aPD-1.In this study,a novel mannosylated chitosan(MC)-modified ethosome(Eth-MC)was obtained through electrostatic adsorption.The Eth-MC loaded with plasmid containing the IL-12 gene(pIL-12@Eth-MC)stimulated DCs to express mature-related molecular markers such as CD86,CD80,and major histocompatibility complex-II in a targeted manner.The pIL-12@Eth-MC was then mixed with polyvinyl pyrrolidone solution to make microspheres using the electrospray technique,and sprayed onto the surface of electrospun silk fibroin-polyvinyl alcohol nanofibres to obtain a PVP-pIL-12@Eth-MC/silk fibroin-polyvinyl alcohol composite nanofibrous patch(termed a transcutaneous immunization(TCI)patch).The TCI patch showed a good performance on transdermal drug release.Animal experiments on melanoma-bearing mice showed that topical application of the TCI patches promoted the expression of IL-12 and inhibited the growth of tumour.Furthermore,combined application of the TCI patch and aPD-1 showed a stronger anti-tumour effect than aPD-1 monotherapy.The combination therapy significantly promoted the expression of IL-12,interferon-γand tumour necrosis factor-α,the infiltration of CD4+and CD8+T cells into tumour tissues,and thus promoted the apoptosis of tumour cells.The present study provides a convenient and non-invasive strategy for improving the efficacy of immune checkpoint inhibitor therapy.This study was approved by the Institutional Animal Care and Use Committee at Donghua University(approval No.DHUEC-NSFC-2020-11)on March 31,2020.展开更多
基金National Natural Science Foundation of China (Grant No. 81172990)National Development of Significant New Drugs of China (New Preparation and New Technology,Grant No. 2009zx09310-001)+1 种基金National Key Science Research Program of China (973 Program, Grant No. 2009CB930300)Innovation Team of Ministry of Education (Grant No. BMU20110263)
文摘The purpose of this work was to explore the feasibility of ethosomes for improving the anti-arthritic efficacy of topically administered tetrandrine, a bisbenzylisoquinoline alkaloid. Ethosomes were prepared by using the transmembrane pH-gradient loading method and characterized by mean diameter, morphology and entrapment efficiency. The prepared tetrandrine-loaded ethosomes exhibited spherical shape with about 78 nm of average diameter and entrapment efficiency of （52.87±3.81）%, whereas the liposomes had bigger size （99 nm） and higher entrapment efficiency （98.80±0.01）%. In addition, ethosomes exhibited favorable and enhanced penetration behavior as compared with liposomes. More importantly, tetrandrine-loaded ethosomes had a significantly better anti-adjuvant arthritis efficacy in rats compared to liposomes formulation, but no significant difference in the anti-arthritic efficacy between tetrandrine-loaded ethosomes and commercial dexamethasone ointment was observed. These results suggest that ethosomes would be a promising nanocarrier for topical delivery of tetrandrine across skin.
基金Natural Science Foundation of Shanghai,China(No.12ZR1400300)the Innovation Foundation of Donghua University,China(No.EG2015067)+1 种基金the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry,China“111 Project”Biomedical Textile Materials Science and Technology,China(No.B07024)
文摘One key of constructing ideal transdermal drug delivery system(TDDS)is enhancing the percutaneous rate of drugs without sacrificing compatibility.Ethosomes(Eths)have excellent transdermal performance as well as good biocompatibility,and thus been widely used as drug carrier.Hydrogel has good 3-dimensional mesh structure which is convenience for drugs release and storage.In this study,Eths were introduced into silk fibroin(SF)/polyvinyl alcohol(PVA)composite hydrogel to construct a novel TDDS through a green process.The Ethsomes(Eths)-SF/PVA composite hydrogel TDDS showed good mechanical properties(stress:(0.236±0.032)MPa;strain:(65.74±2.45)%).Also,skin fibroblasts can grow and proliferate well on this TDDS,indicating that this material has a good cytocompatibility.Furthermore,with doxorubicin hydrochloride(Dox)as a model drug loaded in ethosomes,in vitro studies showed that this TDDS was able to transdermally release Dox efficiently.Our data suggested this novel system had a good potential for application in TDD,though further evaluative study still needed to carry out.
基金Natural Science Foundation of Shanghai,China(No.12ZR1400300)Fundamental Research Funds for the Central Universities of China+1 种基金"111 Project"Biomedical Textile Materials Science and Technology of China(No.B07024)Open Foundation of State Key Laboratory for Modification of Chemical Fibers and Polymer Materials(No.LK1111)
文摘Ethosomes are permeation-enhancing carriers, which significantly promote drug delivery into skin. Thus,the introduction of ethosomes into electrospun nanofibers may result in good effect on transdermal drug delivery. In this work,a novel ethosome-loaded silk fibroin( SF) /polyethylene oxide( PEO) composite nanofiber was fabricated based on a green electrospinning process. The ethosome-loaded SF /PEO nanofiber was round and smooth as shown by scanning electron microscopy( SEM),and the incorporation of ethosome didn't significantly affect the morphology of the electrospun SF /PEO nanofiber. The data of Fourier transform infrares(FTIR)spectra suggested the existence of ethosome on the SF /PEO nanofiber and the transmission electron microscopy(TEM) clearly showed the distribution of ethosome on the ethosome-loaded SF nanofibers. This ethosome-loaded SF nanofibrous mat may have a promising application in transdermal drug delivery systems.
文摘The aim of the present study is the formulation of mefenamic acid ethosomal gel by hot and cold methods.To prepare the mefenamic acid transdermal gel,ethosomes was selected as colloidal carriers.Ethosomes were prepared by cold and hot methods.The obtained ethosomes were characterized with vesicular diameter,zeta potential,drug content,entrapment efficiency and in-vitro diffusion studies.The five formulations of ethosomes prepared by cold and hot methods were compared.Among the 10 formulations of ethosomes,E5 was considered as the best formulation because of its mean vesicular diameter of 854 nm,zeta potential of 20 mV,drug content of 96.3%,entrapment efficiency of 94.4%,sustained drug release for 12 hr,i.e.94.4.Then the E5 formulations was incorporated into gel.A comparative study was made between the plain gel and the ethosomal gel.The Ethosomal gel was considered the best because of its highest drug content spreadability,pH(6.9)and the sustained drug release profile for 12 hr.By comparison,the cold method shows better results.
基金supported by the Science&Technology Commission of Shanghai Municipality of China,Nos.18490740400,20DZ2254900the National Key Research&Development Program of China,No.2018YFC1706200.
文摘Recent studies have suggested that the anti-tumour effect of the programmed cell death protein 1 monoclonal antibody(aPD-1)depends on the expression of interleukin-12(IL-12)by dendritic cells(DCs).Since DCs are abundant in skin tissues,transdermal delivery of IL-12 targeting DCs may significantly improve the anti-tumour effect of aPD-1.In this study,a novel mannosylated chitosan(MC)-modified ethosome(Eth-MC)was obtained through electrostatic adsorption.The Eth-MC loaded with plasmid containing the IL-12 gene(pIL-12@Eth-MC)stimulated DCs to express mature-related molecular markers such as CD86,CD80,and major histocompatibility complex-II in a targeted manner.The pIL-12@Eth-MC was then mixed with polyvinyl pyrrolidone solution to make microspheres using the electrospray technique,and sprayed onto the surface of electrospun silk fibroin-polyvinyl alcohol nanofibres to obtain a PVP-pIL-12@Eth-MC/silk fibroin-polyvinyl alcohol composite nanofibrous patch(termed a transcutaneous immunization(TCI)patch).The TCI patch showed a good performance on transdermal drug release.Animal experiments on melanoma-bearing mice showed that topical application of the TCI patches promoted the expression of IL-12 and inhibited the growth of tumour.Furthermore,combined application of the TCI patch and aPD-1 showed a stronger anti-tumour effect than aPD-1 monotherapy.The combination therapy significantly promoted the expression of IL-12,interferon-γand tumour necrosis factor-α,the infiltration of CD4+and CD8+T cells into tumour tissues,and thus promoted the apoptosis of tumour cells.The present study provides a convenient and non-invasive strategy for improving the efficacy of immune checkpoint inhibitor therapy.This study was approved by the Institutional Animal Care and Use Committee at Donghua University(approval No.DHUEC-NSFC-2020-11)on March 31,2020.
