Synthesis, Characterization, and Drug Delivery from pH- and Thermoresponsive Poly(N-Isopropylacrylamide)/Chitosan Core/Shell Nanocomposites Made by Semicontinuous Heterophase Polymerization

Abstract

Temperature- and pH-responsive core/shell nanoparticles were prepared by semicontinuous heterophase polymerization of N-isopropylacrylamide (NIPA) in the presence of chitosan micelles for drug delivery purposes. Micelles of chitosan, formed in an acetic acid aqueous solution at 70°C containing potassium persulfate, were fed with N-isopropylacrylamide (NIPA) at a controlled rate, to produce PNIPA/chitosan core/shell nanoparticles of about 350 nm. Then, the crosslinking agent, glutaraldehyde, was added to crosslink the nanoparticles. These nanocomposites were temperature- and pH-responsive, which make them suitable as controlled drug releasing agents. The nanoparticles exhibit thermoreversibility to heating-and-cooling cycles and show different responses depending on the releasing medium’s pH. Drug delivery tests were performed, employing as a model drug, doxycycline hyclate.

Drug Delivery from Stimuli-Responsive Poly(N-isopropylacrylamide-co-N-isopropylmethacrylamide)/Chitosan Core/Shell Nanohydrogels

“…Huang et al obtained pH- and temperature-sensitive PNIPA/CS core/shell nanoparticles by emulsion polymerization with a T VPT of 33.4 °C [ 25 ]. Alvarado et al reported the synthesis of PNIPA/CS core/shell nanoparticles by semi-continuous heterophase polymerization (SHP) with a T VPT of 34 °C [ 26 ]. However, the T VPT of these nanoparticles is lower than the temperatures in the human body in response to infection.…”

“…Huang et al reported a lower amount of drug released from NIPA/CS core/shell nanoparticles at alkaline pH than at acidic pH [ 23 ]. Alvarado et al on the release of doxycycline hyclate from NIPA/CS core/shell nanocomposites also reported that at alkaline pH, the amount released was much lower than at acidic pH [ 26 ].…”

“…NIPA, with a purity of 99%, was from Acros Organics (Waltham, MA, USA). Chitosan (CS) with a degree of de-acetylation of 68% [ 26 ]; NIPMA, 97% pure; the crosslinker N, N′-methylenbisacrylamide (NMBA), 99% pure; Brij 58, employed as the surfactant, and glutaraldehyde ((GA), 50% in water) were all from Sigma-Aldrich. The initiator, potassium persulfate (KPS), was ACS grade from Fermont.…”