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

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.

Disordering of Starch Films as a Factor Influencing the Release Rate of Biologically Active Substances

“…Furthermore, biodegradable polymeric carrier materials are becoming increasingly common in pharmaceutics for designing capsules, films, aerogels, and emulsions to be administered through the oral, buccal, sublingual, ocular, and transdermal routes. The applicability of polymers for biomedical purposes is determined by the drug release kinetics [ 13 , 14 ], which largely depends on the physical properties of the polymeric matrix (particle shape and size, porosity, and swelling capacity) [ 15 ]. In terms of chemical properties, the drug release rate is expected to be related to the polymer structure; thus, linear and amorphous polymers are supposed to be dissolved and hydrolyzed faster than branched and crystalline ones [ 16 ].…”

“…), as well as spatial distribution of paramagnetic molecules (spin probes) in the matrix [ 17 , 18 , 19 ]. Thus, the use of nitroxide radicals as a spin probe allows one to observe the mobility of dopant molecules at different stages of their release from the polymer matrix [ 15 , 20 ].…”

Spin-Labeled Diclofenac: Synthesis and Interaction with Lipid Membranes

“…Different variants of esterification and amidation reactions are well developed and widely used for the synthesis of esters and amides of many drugs [ 25 , 26 , 27 , 28 ]. For example, spin-labeled esters and amides of aspirin [ 29 ], ibuprofen [ 30 ], indomethacin [ 31 ] and diclofenac [ 32 , 33 ] were synthesized for their study using EPR. However, the loss of the carboxyl group in the original molecule of drugs is a significant drawback for their use as model objects of study.…”

pH of Water Intercalated into Graphite Oxide as Determined by EPR Spectroscopy

“…pH-sensitive spin probe method is a powerful tool for pH-measurements in systems which cannot be analyzed using macroscopic pH measuring equipment [24], [25], [26], [27]. This technique is extensively used for study of polymers [28] [29], biological membranes and proteins [30], [31], in vivo objects [32], [33], nanomaterials [34], [35] etc. In works [25], [32], [33],[36] pH-sensitive nitroxides were used for 3D-mapping of biological tissues and tumors.…”