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

Overview

Journal Polymers (Basel)

Publisher MDPI

Date 2020 Dec 23

PMID 33353203

Citations 3

Authors

Natalia A Chumakova

Elena N Golubeva

Sergei V Kuzin

Tatiana A Ivanova

Igor A Grigoriev

Sergey V Kostjuk

Mikhail Ya Melnikov

Affiliations

Soon will be listed here.

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.

Citing Articles

Spin-Labeled Diclofenac: Synthesis and Interaction with Lipid Membranes.

Baranov D, Kashnik A, Atnyukova A, Dzuba S Molecules. 2023; 28(16).

PMID: 37630243 PMC: 10458756. DOI: 10.3390/molecules28165991.

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

Podgorbunskikh E, Kuskov T, Matveeva A, Ulihin A, Bychkov A, Lomovskiy I Polymers (Basel). 2023; 15(10).

PMID: 37242877 PMC: 10222158. DOI: 10.3390/polym15102303.

Solute Diffusion into Polymer Swollen by Supercritical CO by High-Pressure Electron Paramagnetic Resonance Spectroscopy and Chromatography.

Gromov O, Kostenko M, Petrunin A, Popova A, Parenago O, Minaev N Polymers (Basel). 2021; 13(18).

PMID: 34577959 PMC: 8466873. DOI: 10.3390/polym13183059.

References

Lindner W, Lippold B . Drug release from hydrocolloid embeddings with high or low susceptibility to hydrodynamic stress. Pharm Res. 1995; 12(11):1781-5. DOI: 10.1023/a:1016238427313. View

Messaritaki A, Black S, van der Walle C, Rigby S . NMR and confocal microscopy studies of the mechanisms of burst drug release from PLGA microspheres. J Control Release. 2005; 108(2-3):271-81. DOI: 10.1016/j.jconrel.2005.08.010. View

Kirilyuk I, Bobko A, Khramtsov V, Grigorev I . Nitroxides with two pK values--useful spin probes for pH monitoring within a broad range. Org Biomol Chem. 2005; 3(7):1269-74. DOI: 10.1039/b418707e. View

Raman C, Berkland C, Kim K, Pack D . Modeling small-molecule release from PLG microspheres: effects of polymer degradation and nonuniform drug distribution. J Control Release. 2005; 103(1):149-58. DOI: 10.1016/j.jconrel.2004.11.012. View

Antheunis H, van der Meer J, de Geus M, Heise A, Koning C . Autocatalytic equation describing the change in molecular weight during hydrolytic degradation of aliphatic polyesters. Biomacromolecules. 2010; 11(4):1118-24. DOI: 10.1021/bm100125b. View

Huang J, Mazzara J, Schwendeman S, Thouless M . Self-healing of pores in PLGAs. J Control Release. 2015; 206:20-9. DOI: 10.1016/j.jconrel.2015.02.025. View

Ramchandani M, Robinson D . In vitro and in vivo release of ciprofloxacin from PLGA 50:50 implants. J Control Release. 1998; 54(2):167-75. DOI: 10.1016/s0168-3659(97)00113-2. View

Grizzi I, Garreau H, Li S, Vert M . Hydrolytic degradation of devices based on poly(DL-lactic acid) size-dependence. Biomaterials. 1995; 16(4):305-11. DOI: 10.1016/0142-9612(95)93258-f. View

Giandalia G, De Caro V, Cordone L, Giannola L . Trehalose-hydroxyethylcellulose microspheres containing vancomycin for topical drug delivery. Eur J Pharm Biopharm. 2001; 52(1):83-9. DOI: 10.1016/s0939-6411(01)00145-x. View

10.

Shen E, Kipper M, Dziadul B, Narasimhan B . Mechanistic relationships between polymer microstructure and drug release kinetics in bioerodible polyanhydrides. J Control Release. 2002; 82(1):115-25. DOI: 10.1016/s0168-3659(02)00125-6. View

11.

Huang X, Brazel C . On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release. 2001; 73(2-3):121-36. DOI: 10.1016/s0168-3659(01)00248-6. View

12.

Wang Y, Pan J, Han X, Sinka C, Ding L . A phenomenological model for the degradation of biodegradable polymers. Biomaterials. 2008; 29(23):3393-401. DOI: 10.1016/j.biomaterials.2008.04.042. View

13.

Fredenberg S, Wahlgren M, Reslow M, Axelsson A . The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems--a review. Int J Pharm. 2011; 415(1-2):34-52. DOI: 10.1016/j.ijpharm.2011.05.049. View

14.

Sevim K, Pan J . A model for hydrolytic degradation and erosion of biodegradable polymers. Acta Biomater. 2017; 66:192-199. DOI: 10.1016/j.actbio.2017.11.023. View

15.

Stewart S, Dominguez-Robles J, Donnelly R, Larraneta E . Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications. Polymers (Basel). 2019; 10(12). PMC: 6401754. DOI: 10.3390/polym10121379. View

16.

Peppas N . 1. Commentary on an exponential model for the analysis of drug delivery: Original research article: a simple equation for description of solute release: I II. Fickian and non-Fickian release from non-swellable devices in the form of slabs, spheres,.... J Control Release. 2014; 190:31-2. View

17.

Reinhold S, Desai K, Zhang L, Olsen K, Schwendeman S . Self-healing microencapsulation of biomacromolecules without organic solvents. Angew Chem Int Ed Engl. 2012; 51(43):10800-3. PMC: 3817563. DOI: 10.1002/anie.201206387. View

18.

Fu Y, Kao W . Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems. Expert Opin Drug Deliv. 2010; 7(4):429-44. PMC: 2846103. DOI: 10.1517/17425241003602259. View

19.

Strobel C, Bormann N, Kadow-Romacker A, Schmidmaier G, Wildemann B . Sequential release kinetics of two (gentamicin and BMP-2) or three (gentamicin, IGF-I and BMP-2) substances from a one-component polymeric coating on implants. J Control Release. 2011; 156(1):37-45. DOI: 10.1016/j.jconrel.2011.07.006. View

20.

Gentile P, Chiono V, Carmagnola I, Hatton P . An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering. Int J Mol Sci. 2014; 15(3):3640-59. PMC: 3975359. DOI: 10.3390/ijms15033640. View