The Effect of Fluid Shear Stress on the In Vitro Release Kinetics of Sirolimus from PLGA Films

Polymers

Zhaowei Chu¹  Quan Zheng²  Yubo Fan²  Hongyan Kang²  Xiao Yang²  Xiaoming Li² 

[1] Beijing Key Laboratory of Rehabilitation Technical Aids for Old-Age Disability, National Research Center for Rehabilitation Technical Aids, Beijing 100176, China;School of Biological Science and Medical Engineering, Beihang University, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing 100083, China;

关键词: sirolimus release;    PLGA degradation;    uniform shear stress;    parallel plate flow chamber;    drug-eluting stent;    biodegradable coating;    hemodynamics;   

DOI  :  10.3390/polym9110618

来源: DOAJ

【 摘 要 】

Drug-carrying coatings of stents implanted in blood vessels are exposed to various blood flows. This study investigated the effect of fluid shear stress on the in vitro release kinetics of sirolimus from poly(lactic-co-glycolic acid) (PLGA) films. The homemade parallel plate flow chamber was used to exert quantitative shear stress on the sirolimus-carrying film. By adjusting the flow rate of the release media in the chamber, three levels of shear stress (3.6, 12.0, and 36.0 dyn/cm2) were respectively applied. For each level of shear stress employed, the release kinetics of sirolimus from the PLGA films exhibited a four-phase profile: an initial burst release phase (Phase I), a lag phase (Phase II), a second burst release phase (Phase III), and a terminal release phase (Phase IV). During Phases I and II, sirolimus was released slowly and in small amounts (<10%); however, during Phases III and IV, the drug release increased considerably. Comparisons of different shear stresses indicated that greater shear stress resulted in earlier and faster sirolimus release, with more cumulative drug release observed. PLGA film degradations (molecular weight reduction, mass loss, and surface topographical variations) were also investigated to better explain the observed drug release behavior. Consequently, fluid shear stress was found to significantly accelerate the release of sirolimus from the PLGA matrices. Therefore, this study could provide a practical method for evaluating the in vitro drug release from polymer matrices under uniform shear stress, and might help improve the design of biodegradable coatings on drug-eluting stents.

【 授权许可】

Unknown