Application of Paclitaxel-loaded EGFR Peptide-conjugated Magnetic Polymeric Liposomes for Liver Cancer Therapy

Developing the methodologies that allow for safe and effective delivery of therapeutic drugs to target sites is a very important research area in cancer therapy.In this study,polyethylene glycol(PEG)-coated magnetic polymeric liposome(MPL)nanoparticles(NPs)assembled from octadecyl quatemized carboxymethyl chitosan(OQC),PEGylated OQC,cholesterol,and magnetic NPs,and functionalized with epithelial growth factor receptor(EGFR)peptide,were successfully prepared for in-vivo liver targeting.The two-step liver targeting strategy,based on both magnetic force and EGFR peptide conjugation,was evaluated in a subcutaneous hepatocellular carcinoma model of nude mouse.The results showed that EGFR-conjugated MPLs not only accumulated in the liver by magnetic force,but could also diffuse into tumor cells as a result of EGFR targeting.In addition,paclitaxel(PTX)was incorporated into small EGFR-conjugated MPLs(102.0土0.7 nm),resulting in spherical particles with high drug encapsulation efficiency(>90%).The use of the magnetic targeting for enhancing the transport of PTX-loaded EGFR-conjugated MPLs to the tumor site was further confirmed by detecting PTX levels.In conclusion,PTX-loaded EGFR-conjugated MPLs could potentially be used as an effective drug delivery system for targeted liver cancer therapy.

Alginate-coated quaternized chitosan nanoparticles for oral delivery of insulin

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.