Electrospinning of thermo-and pH-sensitive polymers as potential drug delivery systems

Abstract

This project aims to obtain an electrospun membrane of poly(N-vinylcaprolactam) (PNVCL), a thermosensitive polymer, as a drug delivery system. The advantage of the use of this polymer and of the manufacturing method adopted for this application lies in the thermosensitive nature of the polymer, which could allow controlled drug release, and the high specific surface area of the membranes. Several routes have been tested to obtain these membranes. During a first step, membranes of PNVCL and its mixtures with poly(ε-caprolactone) (PCL) were obtained. These were tested for the ability to deliver ketoprofen, a hydrophobic drug, in a controlled manner. Even if membranes were obtained, they did not exhibit the stability of morphology necessary for their use. Indeed, upon contact with water they dissolved which resulted in too rapid drug release. In order to solve these two problems, the PNVCL was modified to obtain both thermo-and pHsensitive copolymer poly(N Vinylcaprolactam-co-acrylic acid) (Poly (NVCL-co-AA)). Two nominal compositions of this copolymer were studied, a copolymer containing 20 and another 30mol% AA. The membranes obtained were tested for their ability to encapsulate and release a hydrophobic substance, ketoprofen, and a hydrophilic substance, caffeine. Regular fibers, the diameter of which increased when the active substance was incorporated, were obtained. The results also showed that while ketoprofen lost its crystalline form when incorporated into fiber, the same was not true for caffeine. The cytotoxicity of the various membranes obtained was evaluated by cell viability tests using cell lines of MTT and mouse embryonic fibroblasts (MEF cells). The release of ketoprofen and caffeine was studied at temperatures of 25 and 42°C and at pH of 1.2 and 7.4. For ketoprofen and caffeine, the release profile showed a higher release rate for a temperature below LCST (lower critical solution temperature: temperature at which polymers undergo distinct water- soluble/non-soluble in water phase transitions) (25oC) indicating a release based on the phenomenon of diffusion. pH has also been shown to affect the release kinetics. The results also showed that the copolymer containing 20 mol% AA was less cytotoxic to cells compared to the 30 mol% AA copolymers. The work carried out led to the development of a novel electrospun drug delivery system able to control the release of the hydrophilic and hydrophobic models of drugs. This system thus presents different release profiles depending on the model used and the conditions set (temperature/pH). The potential of the electrospinning technique as well as the thermo-and pH-sensitive copolymers highlighted in this project have indicated that thermo-and pH-sensitive poly(NVCL-co-AA) are promising candidates for controlling drug release.

Date	15 Nov 2021
Original language	American English
Awarding Institution	École de technologie supérieure
Supervisor	Nicole R. Demarquette (Supervisor) & Amilton M Dos Santos (Co-supervisor)