Development of a thermosensitive grafted drug delivery system—synthesis and characterization of NIPAAm‐based grafts and hydrogel structure

Abstract

A thermosensitive grafted hydrogel was investigated for heating-activated drug release. The hydrogel was created by grafting oligomers of N-isopropylacrylamide-co-acrylamide (AAm) to a poly(2-hydroxyethyl methacrylate), or PHEMA, hydrogel. N-Isopropylacrylamide-co-AAm oligomers were synthesized with a range of compositions to raise the lower critical solution temperature (LCST) above physiological temperature. PHEMA hydrogels with these thermosensitive grafts were synthesized by free-radical solution polymerization, using an acrylated version of the oligomers. The oligomers were characterized for their molecular weight, LCSTs, and rate of response to a change in temperature. With the flexibility in tuning their properties by varying reaction parameters, these oligomers present possibilities in several fields, including drug delivery. The impact of cross-linking agent type and the amount and presence of grafts on the polymer network structure was found by determining the hydrogel mesh sizes. PHEMA gels cross-linked with methylenebisacrylamide had larger mesh sizes than those crosslinked with ethylene glycol dimethacrylate. Increasing amounts of cross-linking agent decreased mesh sizes. LCSTs exhibited by oligomers were slightly lower than those exhibited by polymer gels of the same composition. The grafting reaction was found to have only a slight impact on the hydrogel mesh size.

Engineering a sharp physiological transition state for poly(n‐isopropylacrylamide) through structural control

“…Because of this well‐defined transition, pNIPAAm has been extensively studied by many groups for applications in biotechnology, ranging from protein purification3 to drug delivery4, 5 to biosensing 6. One of the many requirements for successful application in biological systems is an LCST at physiological or higher temperatures 3, 5, 7, 8. For instance, although current technology enables the use of pNIPAAm systems in protein purification from acellular systems,3 increasing the LCST to physiological temperatures would make it possible to use pNIPAAm to extract hydrophilic proteins in the context of a continuing cell culture without extreme stresses on the cells.…”

“…Although several copolymer blends exist to raise the LCST with sharp transitions,9, 10 some of the most popular blends for biological applications such as acrylic acid (AAc) have a widening effect on the LCST. Copolymerization with AAc has the effect of widening the LCST from a transition that occurs over <0.5 °C to a transition that takes place over a range of 5–10 °C or even larger depending on the desired LCST 2, 7, 11. This increase in transition range is due to the inhibition of water exclusion and is less than ideal for any application requiring a sharply defined response 12.…”

Near‐infrared‐active and pH‐responsive fluorescent polymer‐integrated hybrid graphene oxide nanoparticles for the detection and treatment of cancer

“…However, the applicable property of widely tunable spectra, from the visible to NIR region, is relatively less extensively explored, except in recent papers demonstrating the possibility of using 3,4‐propylenedioxyselenophene (ProDOS) as a structural analog of PEDOT for photothermal effects . Thus, we expect that the photothermal applications of PEDOT:PSM and the pH‐responsive bioimaging role of PgP on an integrated hybrid rGO structure will point to the direction of the development of various multifunctional PTT agents …”

Tuning thermoresponsive behavior of diblock copolymers and their gold core hybrids

“…There are many excellent studies on PNIPAM polymers and copolymers [29,30,[36][37][38][39][40][41][42][43][44], but there are fewer studies of the effects of end groups on oligoethylene acrylates or methacrylates [45][46][47]. Recently, Theato and co-workers [45] studied end group effects on very low molecular weight homo poly[oligo(ethylene glycol) methacrylate] (POEGMA) chains (M n $ 3-4 kDa, measured by SEC against polystyrene).…”