Student Award for Outstanding Research Winner in the Undergraduate Category for the 2017 Society for Biomaterials Annual Meeting and Exposition, April 5–8, 2017, Minneapolis, Minnesota: Development and characterization of stimuli‐responsive hydrogel microcarriers for oral protein delivery

Abstract

A family of pH-responsive terpolymers composed of methacrylic acid (MAA), N-vinyl pyrrolidone (NVP), and poly(ethylene glycol) monomethylether monomethacrylate (PEGMMA) have been developed and evaluated for their pH-responsive swelling behavior, protein-loading capabilities, and cytocompatibility. These terpolymer hydrogels, designated as P((MAA-co-NVP)-g-EG), were synthesized with varying PEG chain lengths and monomer feed ratios. The incorporation of MAA into the terpolymer structure was quantified with potentiometric titration. Equilibrium and dynamic swelling studies confirmed the pH-responsive behavior of the hydrogel, with the system remaining collapsed/complexed in acidic pH conditions and swollen/decomplexed in neutral pH conditions. The ability of the hydrogels to partition protein into the swollen network was assessed for two model proteins of varying molecular weight: insulin and porcine growth hormone. Finally, the cytocompatibility of the hydrogels in the presence of two model intestinal cell lines was investigated and confirmed minimal cytotoxicity at and below 2.5 mg/mL. The developed P((MAA-co-NVP)-g-EG) hydrogels exhibit unique properties that could potentially be utilized for drug delivery and separation applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1243-1251, 2017.

Polymeric Hydrogels as Technology Platform for Drug Delivery Applications

“…The oral administration of peptides and proteins has become a great challenge in pharmaceutical research [58,59]. In this context, O’Connor et al [60] developed and characterized systems made of methacrylic acid (MAA), N -vinyl pyrrolidone (NVP) and PEG monomethyl ether monomethacrylate (PEGMMA) for the oral delivery of two proteins of different molecular weight, namely insulin and porcine growth hormone. These terpolymer hydrogels are sensitive to different pH conditions.…”

“…In addition, these hydrogels exhibit promising mucoadhesive properties for interaction with the lining of the upper small intestine mucosa. Finally, the compatibility of the hydrogels in two model intestinal cell lines (colon adenocarcinoma cells, Caco-2, and mature differentiated goblet cells, HT29-MTX) was investigated and a cytotoxicity of at least 2.5 mg/mL was found [60]. More recently, Treenate and Monvisade [61] developed a pH-sensitive hydrogel of hydroxyethylacryl chitosan and sodium alginate cross-linked with different divalent cationic cross-linkers such as Ca 2+ , Zn 2+ and Cu 2+ , and used paracetamol as water-soluble model drug.…”

Transport and delivery of interferon-α through epithelial tight junctions via pH-responsive poly(methacrylic acid-grafted-ethylene glycol) nanoparticles

“…For almost twenty five years, we have investigated intelligent, highly biocompatible carrier systems that can protect and deliver therapeutic agents, especially proteins, to their site of action [30,31,32,33,34]. For these systems to be effective, they also need to enable drug transport to the bloodstream, via a series of paracellular or transcellular mechanisms through the intestinal wall.…”