Poly(N-vinylcaprolactam) and Salicylic Acid Polymeric Prodrug Grafted onto Medical Silicone to Obtain a Novel Thermo- and pH-Responsive Drug Delivery System for Potential Medical Devices.

José M Cornejo-Bravo,Giovanni Palomino-Vizcaino,Mario Curiel-Alvarez,Héctor Magaña,Kenia Palomino,Benjamín Valdez-Salas,Emilio Bucio,Oscar M Pérez-Landeros

doi:10.3390/ma14051065

Abstract

New medical devices with anti-inflammatory properties are critical to prevent inflammatory processes and infections in medical/surgical procedures. In this work, we present a novel functionalization of silicone for medical use with a polymeric prodrug and a thermosensitive polymer, by graft polymerization (gamma rays), for the localized release of salicylic acid, an analgesic, and anti-inflammatory drug. Silicone rubber (SR) films were functionalized in two stages using graft polymerization from ionizing radiation (60Co). The first stage was grafting poly(N-vinylcaprolactam) (PNVCL), a thermo-sensitive polymer, onto SR to obtain SR-g-PNVCL. In the second stage, poly(2-methacryloyloxy-benzoic acid) (P2MBA), a polymeric prodrug, was grafted to obtain (SR-g-PNVCL)-g-P2MBA. The degree of functionalization depended on the concentrations of monomers and the irradiation dose. The films were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy/energy-dispersive X-ray spectrometry (SEM–EDX), thermogravimetric analysis (TGA), and contact angle. An upper critical solution temperature (UCST) of the films was demonstrated by the swelling degree as a temperature function. (SR-g-PNVCL)-g-P2MBA films demonstrated hydrolysis-mediated drug release from the polymeric prodrug, pH, and temperature sensitivity. GC–MS confirmed the presence of the drug (salicylic acid), after polymer hydrolysis. The concentration of the drug in the release media was quantified by HPLC. Cytocompatibility and thermo-/pH sensitivity of functionalized medical silicone were demonstrated in cancer and non-cancer cells.

Highlights

Medical devices are crucial for the success of many medical/surgical procedures today [1]
N-vinylcaprolactam 98% was obtained from Sigma-Aldrich
Toluene played a critical role in this phase, as it helped the swelling of the films, favoring the migration of the monomeric solution throughout the silicone polymeric matrix [55,56]

Summary

Introduction

Medical devices are crucial for the success of many medical/surgical procedures today [1] They are classified based on the type of device, risk, and time of use [2,3]. Class III devices are high risk, and implantation into patients is long or prolonged [5] Examples of these devices are coronary stents, pacemakers, and orthopedic and breast implants [6,7,8]. Some of the most widely used polymers are polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), and silicone rubber (SR) [11,12,13] These polymeric materials have been widely used in medical device production due to their thermal and mechanical stability, biocompatibility, cheap production, and compatibility with many sterilization methods [14,15]. The production of polymeric medical devices from additive manufacturing (3D printing) has increased due to the development of biocompatible scaffolds, precise device design, and minimal waste of materials during production [16,17,18]

Objectives

Methods

Results