Complexation hydrogels for oral insulin delivery: Effects of polymer dosing on in vivo efficacy

Anthony Tuesca, Koji Nakamura, Mariko Morishita, Jeffrey Joseph, Nicholas Peppas, Anthony Lowman

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Hydrogels comprised of poly(methacrylic acid) grafted with poly(ethylene glycol) (P(MAA-g-EG)) were characterized and examined for their potential as oral insulin carriers. Insulin loaded polymer (ILP) samples were made using two different polymer formulations. The values for the effective molecular weight between crosslinks, Me, and the network mesh size, ξ, were characterized and increased with increasing pH levels for both formulations. Insulin uptake studies indicated a high insulin loading efficiency for all samples tested, however release was dependent on the amount of insulin loaded. The effect of total polymer dosing was investigated by in situ administration in isolated ileal segments in rats. All ILP samples induced a hypoglycemic effect and an increase in insulin levels, proving that insulin was still biologically active. Insulin dosing amounts were varied by (i) maintaining a constant insulin fraction within an ILP sample while changing the amount of ILP and (ii) by varying the insulin fraction while dosing with the same amount of ILP. The total insulin absorption was dependent on both the amount of the polymer present and the concentration of insulin within an ILP sample, with a maximum relative bioavailability of 8.0%.

Original languageEnglish (US)
Pages (from-to)2607-2618
Number of pages12
JournalJournal of Pharmaceutical Sciences
Volume97
Issue number7
DOIs
StatePublished - Jul 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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