Predictive modeling of insulin release profile from cross-linked chitosan microspheres

S. Jose, J. F. Fangueiro, J. Smitha, T. A. Cinu, A. J. Chacko, K. Premaletha, E. B. Souto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)


Insulin-loaded microspheres composed of chitosan 3% (w/v), and loading 120 IU insulin were produced by emulsion cross-linking method. Cross-linking time was 5 h and glutaraldehyde 3.5% (v/v) was used as cross-linker. Swelling ratio studies were evaluated to predict release of insulin from chitosan microspheres. Bacitracin and sodium taurocholate were incorporated in the formulations as proteolytic enzyme inhibitor and absorption enhancer, respectively. In vitro insulin release studies were performed in phosphate buffer pH 7.4 and also in HCl pH 2 with and without trypsin. Activity of bacitracin was also evaluated. In vitro release showed a controlled profile up to 12 h and the formulation containing 0.15% (w/v) of bacitracin revealed a maximum biological activity of about 49.1 ± 4.1%. Mathematical modeling using Higuchi and Korsmeyer-Peppas suggested a non-Fickian diffusion as the mechanism of insulin release. Insulin-loaded chitosan microspheres for oral delivery showed to be an innovative and reliable delivery system to overcome conventional insulin therapy.

Original languageEnglish
Pages (from-to)249-253
Number of pages5
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - Feb 2013
Externally publishedYes


  • Bacitracin
  • Chitosan
  • Higuchi model
  • Insulin
  • Korsmeyer-Peppas model microspheres
  • Medicinal chemistry
  • Non-Fickian diffusion
  • Oral delivery


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