Molecular Structure of Physiologically‐Responsive Hydrogels Controls Diffusive Behavior

Abstract

SummaryPolymeric networks and the ensuing hydrogels of methacrylic acid and N-vinyl pyrrolidone were successfully synthesized using a UV-initiated free radical polymerization and characterized to assess their applicability as carriers for directed drug delivery. FT-IR spectroscopy revealed shifts in peak absorbances that indicated the presence of hydrogen bonding complexes between functional groups, while SEM imaging showed that the different comonomers affect the surface morphology of the microparticles. Dynamic pH swelling studies demonstrated the pH responsiveness of the carriers in gastric and intestinal conditions and revealed that systems containing higher concentrations of methacrylic acid experienced the highest degree of hydrogen bonding complexation in gastric conditions. The presence of NVP in the systems enhanced swelling. Equilibrium swelling studies revealed that the mesh size was sufficiently large to allow drug diffusion across the networks.

Surface-Modified P(HEMA-co-MAA) Nanogel Carriers for Oral Vaccine Delivery: Design, Characterization, and In Vitro Targeting Evaluation

“…47 Furthermore, a similar increase in pH transition values was previously reported for various copolymer pH-responsive networks containing MAA. 40,48,49 Owing to this transition, the nanogel particles exhibited an increase in zeta potential and a decrease in z -average diameter as pH was decreased in the experiment; at high pH values, pendent MAA groups are ionized, showing zeta potential values of −45 mV and leading to the dissociation of the interpolymer network. 20 The electrostatic repulsion causes the polymer complex to swell, and hence, z -average diameter values of 961.8 nm to 1.5 µm were observed, depending on the polymer composition (Figure 2).…”

“…These divergences in particle size are probably due to the degree of MAA present in the network; higher contents of ionizable monomer led to higher repulsion and dissociation within the polymer network. Previous studies on MAA copolymerized with N -vinylpyrrolidone (P(MAA- co -NVP)) reported a higher degree of hydrogen bonding complexation at low pH values when higher concentrations of MAA were employed, 49 which accounts for a larger z -average diameter transition in particles with higher contents of MAA. Furthermore, similar results were previously obtained with P(MAA- g -PEG) networks, 17 where a higher MAA feed ratio correlated with the more dynamic change in size on gel nanospheres as the pH was increased.…”

Stimulus-responsive hydrogels: Theory, modern advances, and applications

“…However, efforts in the lab have shifted toward the optimization of different complexation hydrogel networks for the oral delivery of a variety of protein therapeutics. One such example, developed by Carr et al, is P(MAA-co-NVP), a hydrogel network with a backbone composed of a copolymer of MAA and N -vinyl pyrrolidone (NVP) [85]. N -vinyl pyrrolidone is a highly hydrophilic monomer that can be readily polymerized into the backbone of the hydrogel network and possesses desirable properties such as mucoadhesion, minimal toxicity, hydrogen bonding groups, and a neutral charge.…”

Progress in Nanoparticulate Systems for Peptide, Proteins and Nucleic Acid Drug Delivery

“…Good candidates for drug carriers fulfilling the mentioned above requirements are polyanioninc gel microparticles which collapse at low and swell at high pH. Peppas and coworkers described synthesis of gel microparticles made from crosslinked poly{(methacrylic acid)-co-[poly(ethylene glycol) monomethyl ether methacrylate]} (it is poly(methyl methacrylate) with poly(ethylene oxide) grafts), P(MMA-g-PEG), microparticles containing poly[(methacrylic acid)-co-(2-methacryloxyethyl glucoside)] and microparticles from poly[(methcrylic acid)-co-N-vinylpyrrolidone] [71][72][73][74]. Tetraethylene dimethacrylate was used as a crosslinking agent in synthesis of microparticles.…”