Physicochemical behavior and cytotoxic effects of p(methacrylic acid–g-ethylene glycol) nanospheres for oral delivery of proteins

Abstract

The challenges faced to orally deliver therapeutic agents with unfavorable physicochemical properties, such as proteins, have been the primary motivation for the design and development of novel oral delivery systems that could circumvent biological barriers. In this work, we examined complexation-sensitive hydrogel nanospheres composed of poly[methacrylic acid-grafted-poly(ethylene glycol)] (P(MAA-g-EG)), on a model biological environment. For this purpose, a gastrointestinal cell culture model, the Caco-2 cell line, was employed to investigate the cytotoxic effects of the polymeric carrier and its effects on the cell monolayer integrity. The determination of the cytotoxic effects of the polymer network on the cell monolayer was performed by a colorimetric assay and by the counting of viable cells using the trypan blue exclusion method. Electrophysiological measurements were performed to measure the transepithelial electrical resistance changes in the monolayers in the presence and absence of the nanosphere suspension. The examination of the physicochemical interactions of the P(MAA-g-EG) nanosphere system with Caco-2 cell monolayers revealed that these systems possessed low cytotoxicity and were capable of opening the tight junctions between epithelial cells, therefore significantly reducing the transepithelial electrical resistance.

Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology

“…For example, pH-responsive hydrogels composed of PEG-containing ionic networks have been applied for the oral delivery of proteins such as insulin [96,97] and calcitonin. [98,99] By incorporating enzymes within environmentally responsive hydrogels, researchers have created drug-delivery systems that are responsive to biological analytes. For example, an important class of polymers for drug delivery are glucose-responsive hydrogels that are based on polymers incorporating glucose oxidase within their network.…”

Calcium alginate nanocarriers as possible vehicles for oral delivery of insulin

“…Apart from these, the other disadvantages include low patient compliance, the high costs of a sterile manufacturing process and the need for qualified personal to administer the injections. Various administration routes of insulin delivery are also reported such as pulmonary delivery [3], transdermal delivery [4], nasal delivery [5] and oral delivery [6].…”

Self-Assembly of Stimuli-Responsive Water-Soluble [60]Fullerene End-Capped Ampholytic Block Copolymer

“…This type of reversible change has far-reaching consequences on aggregation, phase behavior, and solubility, leading to widespread applications in drug delivery systems [22], in devices as actuators [23], artificial muscles, and controlled molecular gates and switches [24] Studies conducted on the stimuli-responsive drug-release behavior of block copolymers have demonstrated their possible applications [25], [26]. Since PMAA and PDMAEMA are proven to be stimuli-responsive and biocompatible [27], studies have been conducted on P(MAA-b-DMAEMA) block copolymers by a few groups. Gohy et al investigated the association behavior of a series of mono-dispersed P(MAA-b-DMAEMA) ampholytic diblock copolymers in water in the dilute regime as a function of pH and concentration [28].…”