ABSTRACT
In the past several decades, polymeric microparticles (MPs) have emerged as viable solutions to address the limitations of standard pharmaceuticals and their corresponding delivery methods. While there are many preclinical studies that utilize polymeric MPs as a delivery vehicle, there are limited FDA-approved products. One potential barrier to the clinical translation of these technologies is a lack of understanding with regard to the manufacturing process, hindering batch scale-up. To address this knowledge gap, we sought to first identify critical processing parameters in the manufacturing process of blank (no therapeutic drug) and protein-loaded double-emulsion poly(lactic-co-glycolic) acid MPs through a quality by design approach. We then utilized the design of experiments as a tool to systematically investigate the impact of these parameters on critical quality attributes (e.g., size, surface morphology, release kinetics, inner occlusion size, etc.) of blank and protein-loaded MPs. Our results elucidate that some of the most significant CPPs impacting many CQAs of double-emulsion MPs are those within the primary or single-emulsion process (e.g., inner aqueous phase volume, solvent volume, etc.) and their interactions. Furthermore, our results indicate that microparticle internal structure (e.g., inner occlusion size, interconnectivity, etc.) can heavily influence protein release kinetics from double-emulsion MPs, suggesting it is a crucial CQA to understand. Altogether, this study identifies several important considerations in the manufacturing and characterization of double-emulsion MPs, potentially enhancing their translation.
ABSTRACT
Immune homeostasis is maintained by a precise balance between effector immune cells and regulatory immune cells. Chronic deviations from immune homeostasis, driven by a greater ratio of effector to regulatory cues, can promote the development and propagation of inflammatory diseases/conditions (i.e., autoimmune diseases, transplant rejection, etc.). Current methods to treat chronic inflammation rely upon systemic administration of non-specific small molecules, resulting in broad immunosuppression with unwanted side effects. Consequently, recent studies have developed more localized and specific immunomodulatory approaches to treat inflammation through the use of local biomaterial-based delivery systems. In particular, this review focuses on (1) local biomaterial-based delivery systems, (2) common materials used for polymeric-delivery systems and (3) emerging immunomodulatory trends used to treat inflammation with increased specificity.
