Small intestine- and colon-specific smart oral drug delivery system with controlled release characteristic

Abstract

In recent years, there has been a significant increase in strategies for the development of small intestine (and colon)-specific oral drug-delivery systems to maximize the efficiency of therapeutic agents and reduce side effects. However, only a few strategies are capable of working in the complicated environment of the human intestinal tract. In this study, the preparation of a basic pH/temperature-responsive co-polymer (p-NIVIm) and its in-vitro-drug delivery function in the pH range of 1-8 and temperature range of 25-42 °C are reported. The basic copolymer was prepared by radical copolymerization of N-isopropyl acryl amide (NIPAAm) and N-vinylimidazole (VIm). The lower critical solution temperature (LCST) of p-NIVIm was higher in stomach pH (~1.0) conditions (36.5-42 °C) and lower in small intestine and/or colon pH (~8.0) conditions (35.8-38.2 °C). The ability to uptake a model protein (BSA) at body temperature and to release it in conditions of 37 °C and pH 1-8 was determined. The drug loading capacity (0.231 mg per 1.0 mg copolymer) and efficiency (92.4%) were high at 37 °C/pH 7. The drug carrier showed a slow release pattern at pH 1 (~0.084 mg; ~35%) and then a sudden release pattern (~0.177 mg; ~73%) at pH 8. The cytotoxicity of p-NIVIm to MCF-7 cells in vitro was minimal at concentrations <168.9 μg/mL after 72 h. The prepared copolymer with its pH-/temperature-responsive protein-entrapping and -releasing behavior at body temperature may potentially be applied as a novel small intestine (and colon)-specific oral drug delivery system.

Keywords: Colon; Controlled delivery; Oral drug-delivery systems; Small intestine; pH- and temperature-responsive copolymer.