Characterization of Thermoresponsive Poly-N-Vinylcaprolactam Polymers for Biological Applications

Abstract

Poly-N-Vinylcaprolactam (PNVCL) is a thermoresponsive polymer that exhibits lower critical solution temperature (LCST) between 25 and 50 °C. Due to its alleged biocompatibility, this polymer is becoming popular for biomedical and environmental applications. PNVCL with carboxyl terminations has been widely used for the preparation of thermoresponsive copolymers, micro- and nanogels for drug delivery and oncological therapies. However, the fabrication of such specific targeting devices needs standardized and reproducible preparation methods. This requires a deep understanding of how the miscibility behavior of the polymer is affected by its structural properties and the solution environment. In this work, PNVCL-COOH polymers were prepared via free radical polymerization (FRP) in order to exhibit LCST between 33 and 42 °C. The structural properties were investigated with NMR, FT-IR and conductimetric titration and the LCST was calculated via UV-VIS and DLS. The LCST is influenced by the molecular mass, as shown by both DLS and viscosimetric values. Finally, the behavior of the polymer was described as function of its concentration and in presence of different biologically relevant environments, such as aqueous buffers, NaCl solutions and human plasma.

Thermoresponsive Chitosan-Grafted-Poly(N-vinylcaprolactam) Microgels via Ionotropic Gelation for Oncological Applications

“…The data disagreed with the LCST-molecular-mass dependence previously reported by Meeussen [144,145], Kirsh [201] and, later, by Cortez-Lemus [24]. According to Meeuseen's predictions, PNVCL must be at least 40 KDa to exhibit LCST lower than 35 • C [145,202], even though the Meeusen study did not account for PNVCL with carboxyl group terminations. Although it is known that the presence of terminations of compounds that enhance the hydrophilicity of PNVCL are known to increase the LCST of the polymer [203,204], the article did not provide an explanation for such a huge difference in the molecular mass values related to the LCST.…”

“…This seems apparently unreasonable considering the high molar ratio (122:1) used for the synthesis of PNVCL-COOH [14]. Despite the lack of insight about the miscibility behaviour of PNVCL-COOH, the following works on the development of CP-based delivery systems seem to neglect the problematic aspects of Prabaharan's work [12,16,18,20,192,202].…”

Precise Synthesis and Thermoresponsive Property of Poly(ethyl glycidyl ether) and Its Block and Statistic Copolymers with Poly(glycidol)

“…The dehydration reaction is accompanied by the entanglement of polymer chains when the temperature is higher than T cp , and its hydrophilicity, hydrophobicity, volume, micelle structure, etc., will change significantly as the temperature changes [24][25][26]. In recent years, poly(ethylene glycol) (PEG) [27], poly(N-isopropylacrylamide) (PNIPAM) [15], poly(poly-2-dimethylaminoethyl methacrylate) (PDMAEMA) [28], poly(N-vinyl caprolactam) (PNVCL) [29], poly(diethyl vinylphosphonate) (PDEVP) [30], and poly(oligoethylene glycol methacrylate) (POEGMA) [31], etc., have been widely studied.…”

Chitosan-Based Biocompatible Copolymers for Thermoresponsive Drug Delivery Systems: On the Development of a Standardization System

“…The small variation accounts for the fact that the length of the polymer has a minimal influence on the value of the LCST. In the case of "type I" polymers such as PNVCL, it is of crucial importance to consider that their solubility depends on the concentration and molecular mass to ensure the reproducibility of the synthesis process [112,[156][157][158][159][160][161].…”

“…Accordingly, the LCST point should be attributed to the point at which phase separation is observed, while the T CP point is associated with solution turbidity and the formation of heterogeneous milky phases [96,162]. TheT CP of a polymer can be easily modified via copolymerization [163][164][165][166] and end group modification [160,161] to tune the hydrophilic-hydrophobic balance of the polymer chains. Moreover, polymer-polymer, polymer-solvent and solvent-solvent interactions can be changed by using different polymer concentrations [96,127,161,167] and ionic strengths [96,127,161,168] and by mixing different polymers [96,127,169], which eventually results in the modification of the T CP .…”