New Insight into the Mechanism of Drug Release from Poly(d,l-lactide) Film by Electron Paramagnetic Resonance.

Tatiana A Ivanova,Sergey V Kostjuk,Elena N Golubeva,Igor A Grigoriev,Natalia A Chumakova,Mikhail Ya Melnikov,Sergei V Kuzin

doi:10.3390/polym12123046

Abstract

A novel approach based on convolution of the electron paramagnetic resonance (EPR) spectra was used for quantitative study of the release kinetics of paramagnetic dopants from poly(d,l-lactide) films. A non-monotonic dependence of the release rate on time was reliably recorded. The release regularities were compared with the dynamics of polymer structure changes determined by EPR, SEM, and optic microscopy. The data obtained allow for the conclusion that the main factor governing dopant release is the formation of pores connected with the surface. In contrast, the contribution of the dopant diffusion through the polymer matrix is negligible. The dopant release can be divided into two phases: release through surface pores, which are partially closed with time, and release through pores initially formed inside the polymer matrix due to autocatalytic hydrolysis of the polymer and gradually connected to the surface of the sample. For some time, these processes co-occur. The mathematical model of the release kinetics based on pore formation is presented, describing the kinetics of release of various dopants from the polymer films of different thicknesses.

Highlights

Biodegradable polymers are the class of materials widely used in medicine that degrade in a body environment without producing toxic compounds [1]
In our previous work [35], we demonstrated the possibility of doping polylactide with nitroxide radicals using supercritical carbon dioxide
electron paramagnetic resonance (EPR) spectroscopy combined with modern methods of numerical analysis of spectra allowed for monitoring of the changes in the paramagnetic probe content both in the biodegradable polymeric matrix during hydrolysis and in the external environment simultaneously

Summary

Introduction

Biodegradable polymers are the class of materials widely used in medicine that degrade in a body environment without producing toxic compounds [1]. Polymer materials that decompose within a few hours (e.g., hydroxyethylcellulose) are used for the short-term delivery of medical substances [2]. Polymer forms that are stable in the body for several weeks or months (for example, polylactide and poly(lactide-co-glycolide) copolymers) are applied for the production of temporary prostheses [3,4] as well as for the creation of long-acting drug delivery systems [5]. Biodegradable polymers for medical purposes can be loaded with various bioactives—growth factors, anti-inflammatory drugs, etc. One of Polymers 2020, 12, 3046; doi:10.3390/polym12123046 www.mdpi.com/journal/polymers

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