271075 A Predictive Model for Coupled Polymer Degradation, Erosion, and Drug Release in PLGA Biodegradable Stent Coatings

Tuesday, October 30, 2012: 4:35 PM
Allegheny III (Westin )
Xiaoxiang Zhu and Richard D. Braatz, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA

Drug release from Poly(D,L-lactic-co-glycolic acid) (PLGA) stent coatings typically has multiple stages and is an intricate process controlled by polymer degradation (change of polymer molecular weight), erosion (change of coating mass), and drug transport [1]. Designing such controlled release systems still heavily rely on trial-and-error experimental procedures. While models describing drug delivery from biodurable stent coatings are relatively abundant (e.g., [2, 3]), very limited models are currently available for bulk-eroding PLGA systems that take into account the impact of degradation and erosion on drug release, especially for PLGA stent coatings (e.g., [1, 4]).

This work focuses on the development of a predictive model for the coupled degradation, erosion, and drug release in PLGA stent coatings. Analytical expressions of PLGA coating degradation and erosion are derived, which greatly reduces the complexity of using a computational intensive model such as in [5]. The analytical model demonstrate good predictions of polymer molecular weight and coating erosion rates in different experiments reported in the literature [6-8]. Then an integrated model of drug release from a PLGA coating is presented. Simultaneous drug diffusion transport through the polymer matrix and pores is modeled for the first time for a stent coating and the model is validated for in vitrosirolimus release with good agreement with the experimental data in [6]. Such a contribution of drug release from diffusion through the porous structure is often overlooked in published models that assume the drug diffusivity is constant or solely dependent on polymer molecular weight change. The model developed here is potentially useful for optimizing the design of PLGA coatings to produce target drug release profiles.  


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[2]        S. Venkatraman and F. Boey, "Release profiles in drug-eluting stents: Issues and uncertainties," Journal of Controlled Release, vol. 120, p. 149-160, 2007.

[3]        X. Zhu, D. W. Pack, and R. D. Braatz, "Modelling intravascular delivery from drug-eluting stents with biodurable coating: investigation of anisotropic vascular drug diffusivity and arterial drug distribution," Computer Methods in Biomechanics and Biomedical Engineering, p. 1-12, 2012.

[4]        A. N. Ford, R. D. Braatz, and D. W. Pack, "Multi-Scale Modeling of PLGA Microparticle Drug Delivery Systems," in Proceedings of the 21st European Symposium on Computer Aided Process Engineering (ESCAPE-21), Chalkidiki, Greece, 2011, p. 1475-1479.

[5]        X. Zhu and R. D. Braatz, "Mathematical Modeling of Intravascular Drug Delivery In Drug-Eluting Stents with Biodegradable Coating," in AIChE Annual Meeting, Minneapolis, MN, 2011.

[6]        X. T. Wang, S. S. Venkatraman, F. Y. C. Boey, J. S. C. Loo, and L. P. Tan, "Controlled release of sirolimus from a multilayered PLGA stent matrix," Biomaterials, vol. 27, p. 5588-5595, 2006.

[7]        R. P. Batycky, J. Hanes, R. Langer, and D. A. Edwards, "A theoretical model of erosion and macromolecular drug release from biodegrading microspheres," Journal of Pharmaceutical Sciences, vol. 86, p. 1464-1477, 1997.

[8]        T. Xi, R. Gao, B. Xu, L. Chen, T. Luo, J. Liu, Y. Wei, and S. Zhong, "In vitro and in vivo changes to PLGA/sirolimus coating on drug eluting stents," Biomaterials, vol. 31, p. 5151-5158, 2010.

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