Hybrid responsive hydrogel carriers for oral delivery of low molecular weight therapeutic agents

Abstract

Hydrogels have been influential in the development of controlled release systems for a wide variety of therapeutic agents. These materials are attractive as carriers for transmucosal and intracellular drug delivery because of their inherent biocompatibility, tunable physicochemical properties, basic synthesis, and ability to be physiologically responsive. Due to their hydrophilic nature, hydrogel-based carrier systems are not always the best systems for delivery of small molecular weight, hydrophobic therapeutic agents. In this work, versatile hydrogel-based carriers composed of copolymers of methyl methacrylate (MMA) and acrylic acid (AA) were designed and synthesized to create formulations for oral delivery of small molecular weight therapeutic agents. Through practical material selection and careful design of copolymer composition and molecular architecture, we engineered systems capable of responding to physiological changes, with tunable physicochemical properties that are optimized to load, protect, and deliver their payloads to their intended site of action. The synthesized carriers’ ability to respond to changes in pH, to load and release small molecular weight drugs, and biocompatibility were investigated. Our results suggest these hydrophilic networks have great potential for controlled delivery of small-molecular weight, hydrophobic and hydrophilic agents.

Effect of network mesh size and swelling to the drug delivery from pH responsive hydrogels

“…Hydrogel films composed of the copolymers MMA and AA–P(MMA‐ co ‐AA) were synthesized using UV initiated photopolymerizations as summarized previously . Three different blends of the copolymers of AA and MMA were synthesized.…”

“…Similarly, Caldorera‐Moore et al . developed anionic coblended networks of poly(methyl methacrylate‐ co ‐acrylic acid) P(MMA‐ co ‐AA) microparticles, for the oral delivery of two small‐molecular‐weight agents, diltiazem and fluorescein …”

“…To overcome the barriers of loading and responsive release of low‐molecular‐weight drug, the chemical composition of the hydrogel networks must be tailored to produce swelling and release behaviors that allow efficient drug delivery. Previously, our group tailored the chemical composition of MMA‐ co ‐AA microparticles composed of the copolymer blends of MMA/AA to provide a swelling profile optimal for the oral delivery of diltiazem, a hydrophilic, low‐molecular‐weight drug (MW = 414.5 g/mol) and fluorescein, a hydrophobic, low‐molecular‐weight drug (MW = 332.3 g/mol) . The AA, a hydrophilic monomer, in these P(MMA‐ co ‐AA) copolymer networks allowed the aqueous swelling of the hydrogels and improved drug solubility.…”

“…The AA, a hydrophilic monomer, in these P(MMA‐ co ‐AA) copolymer networks allowed the aqueous swelling of the hydrogels and improved drug solubility. Whereas, the methyl methacrylate, a more hydrophobic monomer, allowed the hydrogels to load and retain the hydrophobic drug effectively . Caldorera‐Moore et al .…”

“…Caldorera‐Moore et al . observed as the amount of MMA in copolymer network increased, the swelling ratio decreased suggesting a decrease in mesh size, but correlated with an increase in loading efficiency …”