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.
Nanomicelles,self-assembling nanosized particles with a hydrophobic core and hydrophilic shell,are currently successfully used as carriers for targeted drug delivery systems via the enhanced permeability and retention（EPR） effect at the tumor sites.In this study,a near-infrared fluorescent cyanine dye（Cy7-NHS） was conjugated to poly（ethylene glycol）-block-poly（ε-caprolactone）（NH 2-PEG-b-PCL）,and the resulting Cy7-PEG-PCL was further mixed with mPEG-b-PCL to form nanomicelles as carriers for paclitaxel（PTX） delivery.Our results showed that the selected mPEG 4000-b-PCL 2500 copolymers self-assembled to form stable micelles with an average size of 30 nm in diameter and a zeta potential of approximately-3 mV.The micelles also exhibited more than 95% encapsulation efficiency of PTX when the molar ratio between paclitaxel and copolymers was 1/4.In vitro cytotoxicity study showed that the PTX-loaded nanomicelles had a similar cell growth inhibition efficacy to that of Taxol against human breast cancer MCF-7 cells.In vivo imaging showed that the Cy7-labeled nanomicelles could be passively targeted to tumor sites effectively after intravenous injection via the tail vein.Also,a strong anti-tumor activity was observed in the nude mice xenografted MCF-7 breast tumor after treatment with PTX-loaded micelles,similar to that of Taxol.As a result,the micelle drug delivery system designed in this paper has great potential in targeted imaging of tumors and chemotherapy.
