Alpha-mangostin(AMG),a natural xanthone extracted from Garcinia mangostana Linn,has a variety of pharmacological therapeutic effects such as antioxidant activity,antibacterial activity,anticancer,and anti-inflammatory...Alpha-mangostin(AMG),a natural xanthone extracted from Garcinia mangostana Linn,has a variety of pharmacological therapeutic effects such as antioxidant activity,antibacterial activity,anticancer,and anti-inflammatory[1].However,it has poor aqueous-solubility and dissolution,which results in low bioavailability.Solid self-emulsifying drug delivery system(solid-SEDDS),an effective pharmaceutical strategy,offers the potential for enhancing the oral bioavailability of poorly water-soluble drugs[2].Therefore,solid-SEDDS is of interest as a potential method for enhancing the solubility and dissolution of AMG.展开更多
The drug formulation design of self-emulsifying drug delivery systems(SEDDS)often requires numerous experiments,which are time-and money-consuming.This research aimed to rationally design the SEDDS formulation by the ...The drug formulation design of self-emulsifying drug delivery systems(SEDDS)often requires numerous experiments,which are time-and money-consuming.This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches.4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods.Random forest(RF)showed the best prediction performance with 91.3% for accuracy,92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation.The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy(89.51%).The central composite design(CCD)was used to screen the best ratio of oil-surfactant-cosurfactant.Finally,molecular dynamic(MD)simulation was used to investigate the molecular interaction between excipients and drugs,which revealed the diffusion behavior in water and the role of cosurfactants.In conclusion,this research combined machine learning,central composite design,molecular modeling and experimental approaches for rational SEDDS formulation design.The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.展开更多
Orally administered peptides or proteins are garnering increasing preference owing to their superiority in terms of patient compliance and convenience.However,the development of oral protein formulations has stalled d...Orally administered peptides or proteins are garnering increasing preference owing to their superiority in terms of patient compliance and convenience.However,the development of oral protein formulations has stalled due to the low bioavailability of macromolecules that encounter the aggressive gastrointestinal environment and harsh mucus villi barrier.Herein,we propose an ideal reverse micelle/self-emulsifying drug delivery system(RM/SEDDS)nanoplatform that is capable of improving the oral bioavailability of hydrophilic peptides by preventing enzymatic degradation and enhancing mucosal permeability.Upon the passage through the mucus,the self-emulsifying drug delivery system with optimal surface properties effectively penetrates the viscoelastic mucosal barrier,followed by the exposure of the inner reverse micelle amphipathic vectors,which autonomously form continua with the lipidic cell membrane and facilitate the internalization of drugs.This membrane-fusion mechanism inaugurates a new way for hydrophilic peptide delivery in the free form,circumventing the traditional impediments of the cellular internalization of nanocarriers and subsequent poor release of drugs.And more importantly,reverse micelles are not spatially specific to the laden drugs,which enables their delivery for a myriad of peptide clinical drugs.In conclusion,as an exquisitely designed nanoplatform,RM/SEDDS overcomes multiple physiological barriers and opens a new path for drug cellular entry,providing new prospects for the development of oral drug delivery systems.展开更多
Objective: To optimize a self-emulsifying drug delivery system(SEDDS) formulation for psoralen and isopsoralen(PSO and IPSO) isolated from Psoraleae Fructus.Methods: A D-optimal design was used to investigate the infl...Objective: To optimize a self-emulsifying drug delivery system(SEDDS) formulation for psoralen and isopsoralen(PSO and IPSO) isolated from Psoraleae Fructus.Methods: A D-optimal design was used to investigate the influence of oil percentage, surfactant percentage and cosurfactant percentage on several properties of SEDDS including particle size, polydispersity,equilibrium solubility, in situ intestine absorption rate and intestinal permeability. Furthermore, the desirability function approach was applied to obtain the optimal formulation for the system.Results: The oil percentage, surfactant percentage and cosurfactant percentage were optimized to be53.6%, 35.7% and 10.7%, respectively, which means the model is available.Conclusions: The D-optimal design is valuable to optimize the SEDDS formulation and understand formulation compositions’ functions on SEDDS properties.展开更多
文摘Alpha-mangostin(AMG),a natural xanthone extracted from Garcinia mangostana Linn,has a variety of pharmacological therapeutic effects such as antioxidant activity,antibacterial activity,anticancer,and anti-inflammatory[1].However,it has poor aqueous-solubility and dissolution,which results in low bioavailability.Solid self-emulsifying drug delivery system(solid-SEDDS),an effective pharmaceutical strategy,offers the potential for enhancing the oral bioavailability of poorly water-soluble drugs[2].Therefore,solid-SEDDS is of interest as a potential method for enhancing the solubility and dissolution of AMG.
基金financially supported by the Science and Technology Development Fund(FDCT)of Macao(0029/2018/A1,China)the University of Macao Research Grants(MYRG2019-00041-ICMS,China)performed in part at the High-Performance Computing Cluster(HPCC)which is supported by Information and Communication Technology Office(ICTO)of the University of Macao,China。
文摘The drug formulation design of self-emulsifying drug delivery systems(SEDDS)often requires numerous experiments,which are time-and money-consuming.This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches.4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods.Random forest(RF)showed the best prediction performance with 91.3% for accuracy,92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation.The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy(89.51%).The central composite design(CCD)was used to screen the best ratio of oil-surfactant-cosurfactant.Finally,molecular dynamic(MD)simulation was used to investigate the molecular interaction between excipients and drugs,which revealed the diffusion behavior in water and the role of cosurfactants.In conclusion,this research combined machine learning,central composite design,molecular modeling and experimental approaches for rational SEDDS formulation design.The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.
基金This work was supported by the National Key Research and Development Program of China(No.2022YFE0107800)National Natural Science Foundation of China(Nos.82073332,and 81673022)。
文摘Orally administered peptides or proteins are garnering increasing preference owing to their superiority in terms of patient compliance and convenience.However,the development of oral protein formulations has stalled due to the low bioavailability of macromolecules that encounter the aggressive gastrointestinal environment and harsh mucus villi barrier.Herein,we propose an ideal reverse micelle/self-emulsifying drug delivery system(RM/SEDDS)nanoplatform that is capable of improving the oral bioavailability of hydrophilic peptides by preventing enzymatic degradation and enhancing mucosal permeability.Upon the passage through the mucus,the self-emulsifying drug delivery system with optimal surface properties effectively penetrates the viscoelastic mucosal barrier,followed by the exposure of the inner reverse micelle amphipathic vectors,which autonomously form continua with the lipidic cell membrane and facilitate the internalization of drugs.This membrane-fusion mechanism inaugurates a new way for hydrophilic peptide delivery in the free form,circumventing the traditional impediments of the cellular internalization of nanocarriers and subsequent poor release of drugs.And more importantly,reverse micelles are not spatially specific to the laden drugs,which enables their delivery for a myriad of peptide clinical drugs.In conclusion,as an exquisitely designed nanoplatform,RM/SEDDS overcomes multiple physiological barriers and opens a new path for drug cellular entry,providing new prospects for the development of oral drug delivery systems.
文摘Objective: To optimize a self-emulsifying drug delivery system(SEDDS) formulation for psoralen and isopsoralen(PSO and IPSO) isolated from Psoraleae Fructus.Methods: A D-optimal design was used to investigate the influence of oil percentage, surfactant percentage and cosurfactant percentage on several properties of SEDDS including particle size, polydispersity,equilibrium solubility, in situ intestine absorption rate and intestinal permeability. Furthermore, the desirability function approach was applied to obtain the optimal formulation for the system.Results: The oil percentage, surfactant percentage and cosurfactant percentage were optimized to be53.6%, 35.7% and 10.7%, respectively, which means the model is available.Conclusions: The D-optimal design is valuable to optimize the SEDDS formulation and understand formulation compositions’ functions on SEDDS properties.
