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.

Chitosan is a natural polysaccharide that is considered to be biocompatible, biodegradable and non-toxic. The polymer has been used in drug delivery applications for its positive charge, which allows for adhesion with and recognition of biological tissues via non-covalent interactions. In recent times, chitosan has been used for the preparation of graft copolymers with thermoresponsive polymers such as poly-N-vinylcaprolactam (PNVCL) and poly-N-isopropylamide (PNIPAM), allowing the combination of the biodegradability of the natural polymer with the ability to respond to changes in temperature. Due to the growing interest in the utilization of thermoresponsive polymers in the biological context, it is necessary to increase the knowledge of the key principles of thermoresponsivity in order to obtain comparable results between different studies or applications. In the present review, we provide an overview of the basic principles of thermoresponsivity, as well as a description of the main polysaccharides and thermoresponsive materials, with a special focus on chitosan and poly-N-Vinyl caprolactam (PNVCL) and their biomedical applications.

Microgels can be considered soft, porous and deformable particles with an internal gel structure swollen by a solvent and an average size between 100 and 1000 nm. Due to their biocompatibility, colloidal stability, their unique dynamicity and the permeability of their architecture, they are emerging as important candidates for drug delivery systems, sensing and biocatalysis. In clinical applications, the research on responsive microgels is aimed at the development of “smart” delivery systems that undergo a critical change in conformation and size in reaction to a change in environmental conditions (temperature, magnetic fields, pH, concentration gradient). Recent achievements in biodegradable polymer fabrication have resulted in new appealing strategies, including the combination of synthetic and natural-origin polymers with inorganic nanoparticles, as well as the possibility of controlling drug release remotely. In this review, we provide a literature review on the use of dual and multi-responsive chitosan-grafted-poly-(N-vinylcaprolactam) (CP) microgels in drug delivery and oncological applications.