Synthesis, evaluation and release studies of NIPA nanopolymers presumed for temperature-controlled drug delivery

Abstract

The copolymers of N-isopropyl acrylamide (NIPA) have been studied extensively as drug carriers for antibacterial, cardiovascular, cytostatic, local anesthetic, and nonsteroidal anti-inflammatory agents, to deliver the required therapeutic effect. The aim of this work was to evaluate the effect of a series of newly synthesized thermosensitive polymeric NIPA derivatives on the release rate of naproxen sodium (NS) from hydrogels composed of hydroxypropyl methylcellulose (HPMC). NIPA derivatives P1-P4 were synthesized by precipitation polymerization without an emulsifier, and their structures were evaluated by NMR spectroscopy. Four formulations were prepared with NS (FP1-FP4), and rate of NS release from these systems was evaluated using a modified pharmacopeial method at 22 and 42°C. The release rate of NS followed a similar trend in all four of the formulations assessed at 22°C, which was the same as the reference formulation. However, the release rate of NS at 42°C was clearly faster in the samples containing the thermosensitive polymers P1-P4 compared with the reference formulation. These results clearly demonstrate that the use of thermosensitive polymeric derivatives of NIPA can increase the release rate of NS from hydrophilic gels based on HPMC.Graphical Abstract Diversity of release courses of naproxen sodium evaluated in formulation containing poly(ethylene glycol) dimethacrylate (PDA, left), and comparison of half-release times (T HR , right) of naproxen sodium formulations containing various thermosensitive polymers P1-P4.

Sustained Drug Release by Thermoresponsive Sol–Gel Hybrid Hydrogels of Poly(N‐Isopropylacrylamide‐co‐3‐(Trimethoxysilyl)Propyl Methacrylate) Copolymers

“…As the data indicate in this figure and in Table , although these are lower than that obtained at 20 °C, still relatively high extent of release is obtained after 360 min (68%–77% in three cases and 51% with the 5.3_G_TEOS sample). These findings are in sharp contrast to literature reports which present higher release above the GCT . These hybrids were made by attaching the PNIPAAm component to preformed smaller or larger dense or porous inorganic particles, and in addition to the interaction with the PNIPAAm phase, the entrapment or adsorption of the drugs in or onto these particles should be taken into account as well.…”

“…However, contradictory findings can be found in the literature. In the cases of a group of PNIPAAm containing hybrids, higher release rates and amount of released drugs are observed at temperatures above the LCST of the hybrid gels . These claim that the gel shrinkage during gel collapse at the LCST affords faster release than that from the swollen gels below the phase transition temperature.…”

“…and references therein). Hybrid gels of PNIPAAm, especially with various forms of silica, which is widely used in industry and in medical practice as well, are of special interest (see, e.g., refs . and references therein).…”

“…Several attempts have recently been reported on the utilization of PNIPAAm hybrid gels containing externally added particles as thermoresponsive drug release matrices . However, contradictory findings can be found in the literature.…”

Synthesis and Formulation of Thermosensitive Drug Carrier for Temperature Triggered Delivery of Naproxen Sodium

“…In the previous scientific work for synthesis potassium persulfate (KPS) was used as an initiator. It is the initiator which forms terminal anionic groups with an acidic nature [24].…”