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.

The gut microbiota is a metabolically active biocatalytic system capable of transforming orally administered xenobiotics through reduction, hydrolysis, deconjugation, and related reactions. Among the most therapeutically tractable applications is the deliberate use of these reactions to activate prodrugs in the gastrointestinal tract. This review applies a strict mechanistic criterion: microbial metabolism must constitute a necessary or deliberately engineered step in generating the active therapeutic moiety. Under this definition, microbiota-activated prodrugs are distinguished from microbiota-mediated drug metabolism, microbiota-targeting interventions, microbiota-assisted delivery, and pH- or reactive oxygen species-responsive systems that do not require microbial chemical activation. This review synthesizes the enzymatic basis of activation, emphasizing azoreductases, β-glucuronidases, reductases, glycosidases, and microbial esterases; defines precision-design principles that prioritize functional rather than taxonomic targets; and examines how interindividual variation in enzyme abundance, expression, and activity can alter prodrug conversion. This review then proposes a causal-validation ladder linking purified enzymes and defined strains to donor microbiota, physiologically relevant gut models, gnotobiotic systems, and quantitative pharmacokinetic/pharmacodynamic studies. Finally, this review discusses companion functional diagnostics, ecological and manufacturing constraints, prospective patient stratification, and enzyme-prodrug co-design. By shifting the field from taxonomic correlation toward mechanism-based functional phenotyping, this review provides a practical framework for developing robust, patient-stratified microbiota-activated therapies in clinical development.