International Journal of Pharmaceutics 2016-01-30

pH-Responsive polymeric micelles based on amphiphilic chitosan derivatives: Effect of hydrophobic cores on oral meloxicam delivery.

Thisirak Woraphatphadung, Warayuth Sajomsang, Pattarapond Gonil, Alongkot Treetong, Prasert Akkaramongkolporn, Tanasait Ngawhirunpat, Praneet Opanasopit

Index: Int. J. Pharm. 497 , 150-60, (2016)

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Abstract

The amphiphilic chitosan derivatives, N-naphthyl-N,O-succinyl chitosan (NSCS), N-octyl-N-O-succinyl chitosan (OSCS) and N-benzyl-N,O-succinyl chitosan (BSCS), were synthesized. Meloxicam (MX) was loaded into polymeric micelles (PMs), and the effects of hydrophobic moieties of the inner core segment on the loading efficiency, stability of MX-loaded PMs, cytotoxicity, drug release, and porcine small intestine permeation were investigated. Among the hydrophobic cores, the N-octyl moiety revealed the highest MX loading efficiency and most stable MX-loaded PMs compared to the other hydrophobic cores. All PMs were spherically shaped (size 213-282 nm) and had low toxicity against Caco-2 cells. The release of MX from PMs was found to be dependent on both hydrophobic cores and hydrophilic shells. In acidic medium at 0-2h, low cumulative MX release was obtained in the MX-loaded OSCS PMs compared to MX-loaded NSCS PMs and MX-loaded BSCS PMs as well as MX free drug. However, when the pH was increased to 6.8, the MX release significantly increased in all MX-loaded PMs. Furthermore, the intestinal permeation rates of MX from all MX-loaded PMs were not significantly different. These results suggest that MX was successfully incorporated into the PMs at high efficiency and good stability by optimizing the hydrophobic moieties of the inner core segments.Copyright © 2015 Elsevier B.V. All rights reserved.