On the Development of Chitosan-Graft-Poly(n-Isopropylacrylamide) by Raft Polymerization Technique

Abstract

The present paper aimed the synthesis of a functional biopolymer based on chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) using the "grafting from" technique via reversible addition-fragmentation chain transfer (RAFT) polymerization. Two different chain transfer agents, both compatible with the acrylic monomer were used. All intermediary products obtained from each step of chemical synthesis were quantified by ATR-FT-IR, 1 H-NMR and elemental analysis. Thermal properties confirmed that, with the chemical modification, chitosan structures became more complex and more thermally stable. The grafting efficiency was quantified as 40% and the final copolymer had double functionality, free amino groups and PNIPAAm segments on the side chains. Thanks to this, water solubility, pH and temperature sensitivity were achieved. The particle size of the aqueous solutions increased from 500 nm to 3.5 µm, with the increase of temperature from 25 to 50 °C. The lower critical solution temperature (LCST) of the solution was determined as 38-42 °C. CS-g-PNIPAAm could be used as a polymeric carrier within a pharmaceutical formulation for topical applications.

Development of Vaginal Carriers Based on Chitosan-Grafted-PNIPAAm for Progesterone Administration

“…Previously, the chitosan copolymer was proven to possess temperature and pH responsivity [ 19 , 25 ] similarly with the formulations based on voriconazole; hydrogels containing progesterone exhibited temperature and pH responsivity with respect to the swelling degree (Q%) and release profile. Another factor influencing the swelling and release parameters was the crosslinking degree given by the addition of polyvinyl alcohol (PVA).…”

“…As it can be observed, Q% had the highest values for sample P1, having least PVA content, particularly at T = 40 °C; determined Q was 4412%, being increased once the temperature was rising. This fact can be explained by the presence of the PNIPAAm segment which induced to the copolymer a LCST temperature of 41 °C [ 25 ]. With the increasing of the PVA content, the hydrogels network became denser, and the matrix was not able to absorb water in the same manner, resulting in a lower swelling degree.…”

“…Chitosan-graft–poly(N-isopropylacrylamide) copolymer (CS-g-PNIPAAm) [ 25 ] was synthesized. The synthesis’ details and experimental set-up were previously presented.…”

“…Graft copolymers of chitosan and poly(N-isopropylacrylamide) (PNIPAAm) showed previously that it may form a viscous hydrogel adherent to the contact surface [ 19 ]. Figure 1 describes the proposed mechanism of the chemical modification of chitosan [ 25 ].…”

Synthesis of Thermoresponsive Chitosan-graft-Poly(N-isopropylacrylamide) Hybrid Copolymer and Its Complexation with DNA

“…Also, nano and microgels made from Chit-g-PNIPAM have been proposed for oncological applications, such as bioactive drug delivery [43] and antibacterial applications [40,44]. Chit-g-PNIPAM copolymers are frequently employed in these applications, with a high proportion of NIPAM molecular units within the grafted Chit-g-PNIPAM structure [23,42,45,46]. Unfortunately, no information has been provided on the synthesis or thermoresponsive behavior of copolymers that cover a wide range of compositions, including those with low and high content of PNIPAM moieties, making it difficult to predict the parameters that determine the sharpness and intensity of the transition, which are critical for this kind of applications.…”