Colon-targeted oral delivery is crucial for the treatment of colon-related diseases, as this delivery strategy enables precise drug administration to the diseased site, enhances drug bioavailability, and improves pati...Colon-targeted oral delivery is crucial for the treatment of colon-related diseases, as this delivery strategy enables precise drug administration to the diseased site, enhances drug bioavailability, and improves patient com- pliance. In particular, nanoparticle-based oral formulations shield drugs from the harsh gastrointestinal environment, and selectively increase drug colon cells, thus elevating concentration inside diseased therapeutic efficacy while reducing systemic toxicity. In this review, we elaborate recent progress in this area, with emphasis on the patho- physiological characteristics of colon site and design strategies to take advantage of these characteristics for colon targeting.展开更多
Oral administration is the best way for the most patients due to the good compliance,and intestinal epithelium is the main barrier of oral drug absorption.In order to overcome the small intestine epithelial barrier to...Oral administration is the best way for the most patients due to the good compliance,and intestinal epithelium is the main barrier of oral drug absorption.In order to overcome the small intestine epithelial barrier to orally deliver water-insoluble drugs,deoxycholic acid(DA),a substrate of the intestinal bile acid transporters,conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)(DA-PEOz-PLA)was designed and synthesized,and deoxycholic acid-modified polymeric micelles composed of DA-PEOz-PLA and mPEG-PLA were fabricated to encapsulate model drug coumarin 6(C6)based on intestinal bile acid pathway.The structure of DA-PEOz-PLA was confirmed using 1 H NMR and TLC,and the molecular weight measured by GPC was 10034 g/mol with a PDI of 1.51.The C6-loaded polymeric micelles with drug loading content of 0.085%were characterized to have 40.11 nm in diameter and uniform spherical morphology observed by TEM.Furthermore,the deoxycholic acid-modified polymeric micelles were demonstrated to further enhance the transmembrane transport efficiency.The mechanic study evidenced that anchorage of deoxycholic acid onto the micelles surface enriched their transcellular transport pathway.Therefore,the designed deoxycholic acid-modified polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs.展开更多
基金supported by the National Natural Science Foundation of China(81471779)the National Thousand Young Talents Programthe Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning
文摘Colon-targeted oral delivery is crucial for the treatment of colon-related diseases, as this delivery strategy enables precise drug administration to the diseased site, enhances drug bioavailability, and improves patient com- pliance. In particular, nanoparticle-based oral formulations shield drugs from the harsh gastrointestinal environment, and selectively increase drug colon cells, thus elevating concentration inside diseased therapeutic efficacy while reducing systemic toxicity. In this review, we elaborate recent progress in this area, with emphasis on the patho- physiological characteristics of colon site and design strategies to take advantage of these characteristics for colon targeting.
基金The National Natural Science Foundation of China(Grant No.81673366).
文摘Oral administration is the best way for the most patients due to the good compliance,and intestinal epithelium is the main barrier of oral drug absorption.In order to overcome the small intestine epithelial barrier to orally deliver water-insoluble drugs,deoxycholic acid(DA),a substrate of the intestinal bile acid transporters,conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)(DA-PEOz-PLA)was designed and synthesized,and deoxycholic acid-modified polymeric micelles composed of DA-PEOz-PLA and mPEG-PLA were fabricated to encapsulate model drug coumarin 6(C6)based on intestinal bile acid pathway.The structure of DA-PEOz-PLA was confirmed using 1 H NMR and TLC,and the molecular weight measured by GPC was 10034 g/mol with a PDI of 1.51.The C6-loaded polymeric micelles with drug loading content of 0.085%were characterized to have 40.11 nm in diameter and uniform spherical morphology observed by TEM.Furthermore,the deoxycholic acid-modified polymeric micelles were demonstrated to further enhance the transmembrane transport efficiency.The mechanic study evidenced that anchorage of deoxycholic acid onto the micelles surface enriched their transcellular transport pathway.Therefore,the designed deoxycholic acid-modified polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs.
