In the present work, we aimed to develop alginate-coated chitosan nanoparticles for oral insulin delivery. The N-[（2-hydroxy- 3-trimethylammonium）propyl] chitosan chloride （HTCC） was synthesized, and the quatemize...In the present work, we aimed to develop alginate-coated chitosan nanoparticles for oral insulin delivery. The N-[（2-hydroxy- 3-trimethylammonium）propyl] chitosan chloride （HTCC） was synthesized, and the quatemized chitosan nanoparticles （HTCC-T NPs） were prepared by ionic gelation of HTCC using tripolyphosphate （TPP）. The alginate-coated quatemized chitosan nanoparticles （HTCC-A NPs） were prepared by coating HTCC-T NPs with alginate （ALG） solution under mild agitation. Particle size, zeta potential, surface morphology, drug loading and entrapment efficiency of HTCC-A NPs were characterized using Zeta-sizer, TEM and HPLC assays. It was found that HTCC-A NPs exhibited uniform spherical particles with the size of （322.2±8.5） nm and positive charges （14.1±0.6） mV. Our data showed that the release behavior of HTCC-A NPs was quite different from that of HTCC-T NPs （without ALG coating） when incubated with various medium at different pH values in vitro, suggesting that ALG coating over the HTCC-T NPs improved the release profile of insulin from the NPs for a successful oral delivery. The ALG coating could also improve the stability of insulin against enzymatic degradation. From circular dichroism spectrum, it was revealed that HTCC-A NPs were capable of maintaining the conformation of insulin. The relative pharmacological bioavailability of HTCC-A NPs was 8.0%±2.5% by intraduodenal administration. The HTCC-A NPs significantly increased （P〈0.05） the relative pharmacological availability （2.2 folds） compared with HTCC-T NPs after oral administration. HTCC-A NPs significantly enhanced the in vivo oral absorption of insulin and exhibited promising potentials for oral delivery.展开更多
基金NSFC projects(Grant No.81273455 and 81072597)grants from Ministry of Education(Grant No.NCET-11-0014 and BM U20110263)the funding support from State Key Laboratory of Long-acting and Targeting Drug Delivery System,LUYE PHARMA
文摘In the present work, we aimed to develop alginate-coated chitosan nanoparticles for oral insulin delivery. The N-[（2-hydroxy- 3-trimethylammonium）propyl] chitosan chloride （HTCC） was synthesized, and the quatemized chitosan nanoparticles （HTCC-T NPs） were prepared by ionic gelation of HTCC using tripolyphosphate （TPP）. The alginate-coated quatemized chitosan nanoparticles （HTCC-A NPs） were prepared by coating HTCC-T NPs with alginate （ALG） solution under mild agitation. Particle size, zeta potential, surface morphology, drug loading and entrapment efficiency of HTCC-A NPs were characterized using Zeta-sizer, TEM and HPLC assays. It was found that HTCC-A NPs exhibited uniform spherical particles with the size of （322.2±8.5） nm and positive charges （14.1±0.6） mV. Our data showed that the release behavior of HTCC-A NPs was quite different from that of HTCC-T NPs （without ALG coating） when incubated with various medium at different pH values in vitro, suggesting that ALG coating over the HTCC-T NPs improved the release profile of insulin from the NPs for a successful oral delivery. The ALG coating could also improve the stability of insulin against enzymatic degradation. From circular dichroism spectrum, it was revealed that HTCC-A NPs were capable of maintaining the conformation of insulin. The relative pharmacological bioavailability of HTCC-A NPs was 8.0%±2.5% by intraduodenal administration. The HTCC-A NPs significantly increased （P〈0.05） the relative pharmacological availability （2.2 folds） compared with HTCC-T NPs after oral administration. HTCC-A NPs significantly enhanced the in vivo oral absorption of insulin and exhibited promising potentials for oral delivery.
