Indomethacin release behaviors from pH and thermoresponsive poly(vinyl alcohol) and poly(acrylic acid) IPN hydrogels for site-specific drug delivery

Abstract

A temperature-and pH-responsive drug delivery system was studied by using interpenetrating polymer network (IPN) hydrogels constructed with poly(acrylic acid) (PAAc) and poly(vinyl alcohol) (PVA). The release of indomethacin incorporated into these hydrogels showed pulsatile patterns in response to both pH and temperature. Indomethacin diffused from the polymer matrices through the swelling and deswelling mechanism. The release amount increased at higher temperature because of the swelling caused by the dissociation of hydrogen bonding. The drastic change of drug release was achieved by alternating pH of the buffer solution and was attributed to the change of states of ionic groups within IPN hydrogels. The free water contents were calculated by using differential scanning calorimetry (DSC), and were proved to be the main factor in the swelling. These results demonstrated that the drug release could be controlled by the swelling/deswelling degree of IPN hydrogels as functions of pH and/or temperature.

Thermoresponsive Polymers for Biomedical Applications

“…Specifically, this requires the polymerization of both networks simultaneously and results in two intermixed networks that can only be separated by breaking bonds. These materials are of interest due to their ability to introduce new properties when the networks interact [95,96] or two different properties when acting independently.…”

“…In contrast to the studies discussed above, where the drug release was slowed by the temperature increase, Shin et al demonstrated a hydrogel with a positive thermoresponse, i.e., drug release increases with increasing temperature [95]. Specifically, an interpenetrating network of polyacrylic acid (PAA) and polyacrylamide (PAAm) forms hydrogels that swell above their upper critical solution temperature, UCST, due to hydrogen bonding between the two different networks being disrupted at higher temperatures allowing the networks to swell [95].…”

“…Specifically, an interpenetrating network of polyacrylic acid (PAA) and polyacrylamide (PAAm) forms hydrogels that swell above their upper critical solution temperature, UCST, due to hydrogen bonding between the two different networks being disrupted at higher temperatures allowing the networks to swell [95]. This preliminary work showed the possibility of increasing drug release with increased temperature [95]. Recent work on the same IPN with grafted β-cyclodextrin showed a faster thermoresponse and lower UCST (35 °C) and a lowered effect of salt on the swelling [96].…”

“…SIPNs consist of a crosslinked network with linear or branched polymer chains penetrating them. An example of this is the SIPN synthesized by Mundargi et al formed from crosslinked gellan gum microspheres with interpenetrating PNIPAAm chains [95]. Drug loading into the microspheres allows for pulsatile drug release.…”

Drug release behavior of a pH/temperature sensitive calcium alginate/poly(N-acryloylglycine) bead with core-shelled structure

“…The unique properties of a smart hydrogel imply that it can be used as a promising material in the biomedical and industrial applications. Some significant applications of hydrogels have been widely investigated including dialysis membranes [11], enzyme immobilization [12], tissue engineering [13], and drug controlled release systems [14][15][16][17] and so on. Among the smart materials, pH-and temperature-sensitive hydrogels have been paid more attentions because the two physiological factors are very important for the human body [18][19][20][21].…”