Self-nanoemulsifying drug delivery systems for oral insulin delivery: In vitro and in vivo evaluations of enteric coating and drug loading

Ping Li, Angel Tan, Clive A. Prestidge, Hanne Mørck Nielsen, Anette Müllertz

Research output: Contribution to journalArticleResearchpeer-review

59 Citations (Scopus)

Abstract

This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w/w), were readily dispersed in water to form nanoemulsions of 35 nm and vesicles of 300 nm. The association efficiency of non-complexed insulin in the dispersed SNEDDS was 18.6%, and was increased to 73.1% for insulin-phospholipid complex (at 10% loading level). The morphology of the dispersed SNEDDS changed from nanoemulsion droplets to vesicular structures with increasing complex loading levels. A pH-dependent insulin release profile was observed for SNEDDS filled into capsules coated with the enteric polymer, Eudragit® L100. Using a Caco-2 cell model, it was observed that the transport of insulin was enhanced by factors of 7.7- and 9.3- for SNEDDS loaded with 2.5 and 10% complex, respectively. In healthy fasted rats, administration of SNEDDS (10% complex) filled in enteric-coated capsules produced a 2.7-fold and 3.4-fold enhancement in the relative bioavailability and glucose reduction, respectively. This study shows the effectiveness of combining SNEDDS (loaded with insulin-phospholipid complex) with enteric-coated capsules for enhancing the oral absorption and efficacy of insulin.

Original languageEnglish
Pages (from-to)390-398
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume477
Issue number1-2
DOIs
Publication statusPublished - 30 Dec 2014
Externally publishedYes

Keywords

  • Enteric coating
  • Hypoglycemia
  • Insulin
  • Oral drug delivery
  • Pharmacokinetic
  • SNEDDS

Cite this