pH‐responsive hydrogels with dispersed hydrophobic nanoparticles for the delivery of hydrophobic therapeutic agents

Abstract

To investigate the delivery of hydrophobic therapeutic agents, a new class of polymer carriers was synthesized. These carriers are composed of two components: (i) a pH-responsive hydrogel composed of methacrylic acid grafted with poly(ethylene glycol) tethers, P(MAA-g-EG), and (ii) hydrophobic poly(methyl methacrylate) (PMMA) nanoparticles. Before the P(MAA-g-EG) hydrogel was crosslinked, PMMA nanoparticles were added to the solution and upon exposure to UV light they were photoencapsulated throughout the P(MAA-g-EG) hydrogel structure. The pH-responsive behavior of P(MAA-g-EG) is capable of triggered release of a loaded therapeutic agent, such as a low molecular weight drug or protein, when it passes from the stomach (low pH) to upper small intestine (neutral pH). The introduction of PMMA nanoparticles into the hydrogel structure affected the swelling behavior, therapeutic agent loading efficiency, and solute release profiles. In equilibrium swelling conditions the swelling ratio of nanoparticle-containing hydrogels decreased with increasing nanoparticle content. Loading efficiencies of the model therapeutic agent fluorescein ranged from 38 – 51 % and increased with increasing hydrophobic content. Release studies from neat P(MAA-g-EG) and the ensuing P(MAA-g-EG) hydrogels containing nanoparticles indicated that the transition from low pH (2.0) to neutral pH (7.0) triggered fluorescein release. Maximum fluorescein release depended on the structure and hydrophobicity of the carriers used in these studies.

Intelligent recognitive systems in nanomedicine

“…Schoener et al investigated two systems that improved the loading and release of hydrophobic drugs like chemotherapeutics by including an interpenetrating network of hydrophobic poly(n-butyl acrylate) [18]. Alternatively, they also encapsulated hydrophobic poly(methyl methacrylate) nanoparticles into the pH-responsive hydrophilic networks [19]. …”

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

“…Several novel hybrid hydrogel materials have recently been developed to overcome this shortcoming [4,16,17]. In their work, Schoener et al [16] developed two types of hybrid hydrogels that had hydrophobic domains within the hydrophilic polymer network.…”

“…To overcome this limitation, Schoener and colleagues developed a second hydrogel architecture composed of P (MAA-g-EG) hydrogels containing hydrophobic poly(methyl methacrylate) (PMMA) nanoparticles [17]. The presence of PMMA nanoparticles in the hydrogel network altered the swelling behavior, loading efficiency, and release profiles of model hydrophobic drugs.…”

Bioactive composites fabricated by freezing-thawing method for bone regeneration applications

“…[20][21][22] The pH-sensitive hydrogels containing polyacrylic acid (PAA) has been widely used in the area of drug-delivery systems principally because of its biocompatibility. 23,24 In addition, pHsensitive polymers consist of pendant acidic or basic group that either accept or release protons in response to changes in environmental pH. Additionally, the incorporation of a copolymer such as PAA that will contribute to hydrogen bonding can increase the strength of the hydrogel.…”