An Oral Delivery System for Insulin

Abstract

Crosslinked 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) copolymer hydrogels were studied as drug delivery systems. Terephthalic acid was covalently linked with 2-hydroxyethyl methacrylate (HEMA), abbreviated as cross-linking agent (CA). Free radical copolymerization of HEMA and MAA with terephthetalic acid (CA) (2, 4, and 6%) as crosslinking agent were carried out at 70°C. The structure of the CA was confirmed by FT-IR, 1H-NMR and 13C-NMR spectroscopy. The composition of the crosslinked three-dimensional polymers were determined by FTIR spectroscopy. Glass transition temperature (Tg) of the network polymers was determined calorimetrically. The effect of copolymer composition on the swelling behavior and hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1) and simulated intestinal fluid (SIF, pH 7.4). The swelling and hydrolytic behavior of the copolymers depended on the content of MAA which caused a decrease in gel swelling in SGF or an increase in gel swelling in SIF. It was observed that in acidic media hydrogen bonds formed due to the protonation of the carboxylic acid groups of the MAA while in more basic or neutral conditions electrostatic repulsion occurred between the ionized carboxylic acid groups. This complex behavior affected the macroscopic swelling properties of the resultant hydrogels. The amount of drug release depended on the degree of hydrogel swelling and crosslinking.

Uptake and Transport of Novel Amphiphilic Polyelectrolyte-Insulin Nanocomplexes by Caco-2 Cells—Towards Oral Insulin

“…The large molecular weight and hydrophilic nature of proteins mean that they cannot diffuse across gastrointestinal tract (GIT) epithelial cells. In addition, enzymes present in the GIT degrade therapeutic proteins such that very little of the protein is available for absorption (9)(10)(11)(12)(13). Several different technologies have been used to facilitate oral protein absorption and prevent degradation.…”

Novel pH-sensitive hydrogels for colon-specific drug delivery

“…Initiation of 2,2-azobisisobutyronitrile (AIBN) was purified by crystallization from methanol. Enzyme-free simulated gastric fluid (SGF) (pH 1) or simulated intestinal fluid (SIF) (pH 7.4) were prepared according to the method described in the literature (Mahkam et al, 2006).…”

New pH-Sensitive Glycopolymers for Colon-Specific Drug Delivery

“…The amount of released drug was determined on a Philips PU 8620 ultraviolet spectrophotometer at the absorption maximum of the free drug in aqueous alkali (λ max = 245 nm) using a 1 cm quartz cell. Enzyme-free simulated gastric fluid (SGF) (pH 1) or simulated intestinal fluid (SIF) (pH 7.4) were prepared by the method described in the literature (Mahkam et al 2006). The HPLC apparatus consisted of Bruker LC-21, equipped with a Bruker UV-Vis detector model LC 313 I, Rheodyne loop injector, and a C18 reverse-phase column of Spherisorb-CN (250 × 4.6 mm id, particle size 5 μm) and was from Bischoff (Germany).…”