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Journal of Chinese Pharmaceutical Sciences ›› 2014, Vol. 23 ›› Issue (12): 823-829.DOI: 10.5246/jcps.2014.12.104

• Original articles • Previous Articles     Next Articles

Alginate-coated quaternized chitosan nanoparticles for oral delivery of insulin

Juan Bai, Jiancheng Wang*   

  1. Department of Pharmaceutics, School of Pharmaceutical Science, Peking University Health Science Center, Beijing 100191, China
  • Received:2014-05-29 Revised:2014-06-04 Online:2014-12-25 Published:2014-06-20
  • Contact: Tel.: 86-10-82805932
  • Supported by:
    NSFC projects (Grant No. 81273455 and 81072597), grants from Ministry of Education (Grant No. NCET-11-0014 and BMU20110263), and the funding support from State Key Laboratory of Long-acting and Targeting Drug Delivery System, LUYE PHARMA.

Abstract:

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 quaternized chitosan nanoparticles (HTCC-T NPs) were prepared by ionic gelation of HTCC using tripolyphosphate (TPP). The alginate-coated quaternized 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 coatingcould 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.

Key words: Quaternized chitosan, Alginate, Insulin, Nanoparticles, Oral delivery

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