Tailoring PLGA nanoparticle release profiles via centrifugal fractioning

Abstract

Event Abstract Back to Event Tailoring PLGA nanoparticle release profiles via centrifugal fractioning Dipankar Dutta1*, Mariama Salifu1*, Rachael W. Sirianni1, 2* and Sarah E. Stabenfeldt1* 1 Arizona State University, School of Biological and Health Systems Engineering, United States 2 Barrow Neurological Institute, Barrow Brain Tumor Research Center, United States Introduction: Poly(D,L-lactic-co­-glycolic) acid (PLGA)-based nanoparticles (NP) are uniquely posed to overcome limitations of conventional drug delivery systems. However, tailoring cargo/payload release profiles from PLGA NPs typically requires the optimization of the multi-parameter NP formulation, where small changes may cause drastic shifts in the resulting release profiles[1],[2]. In this study, we aimed to establish whether refining the average diameter of NP populations through centrifugal fractioning after particle formulation represents a feasible tool to tailor PLGA NP release characteristics. We hypothesized that the average NP size would directly affect protein loading and subsequent release characteristics. Materials and Methods: PLGA NPs were produced via double-emulsion followed by solvent evaporation to encapsulate the model protein, bovine serum albumin (BSA). NPs were then subjected to centrifugal fractioning protocols varying in both spin time and force. After separation of supernatant and pellet, NP size distributions of initial and fractioned groups were determined using scanning electron microscopy. Release profiles were quantified by determining protein encapsulation efficiencies and in vitro release assays. Statistical analyses were performed using analysis of variance with Tukey’s post-hoc test. Results and Discussion: Centrifugal fractioning significantly modulated NP size distribution as a function of spin time and force without negatively affecting yield and NP morphology. Average diameters for all groups in the study ranged between 211.2–707.5nm relative to 340.9nm for the initial batch of NPs. Additionally, we found the average NP diameter was related to marked alterations in encapsulation efficiencies (range: 36.4-49.4%; Fig 1A), burst release (range: 15.8-49.1%; Fig 1B), protein release rate (Fig 1C), and time for total cargo release (range: 38-78 days; Fig 1D). Our data corroborated previous reports relating NP size with such release characteristics[3],[4]. However, this is the first study, to our knowledge, to directly compare NP population size and protein release profile while holding all formulation parameters constant. Conclusion: Previous studies have evaluated the influence of the fabrication parameters on the cargo loading and release from PLGA particles to provide general formulation trends on obtaining broad release profile characteristics. However, seemingly simple changes in the NP formulation may ultimately lead to a loss of desirable attribute(s). We report that protein encapsulation efficiency and several parameters of the release curve are correlated to t. Thus centrifugal fractioning represents a potential tool for tuning NP properties without modifying formulation parameters. Figure 1: Encapsulation efficiency and duration of release was directly proportional to the average particle diameter (A and D). Conversely, the magnitude of the burst release and the rate of protein release were inversely proportional to average particle diameter (B and C). Linear regression was used to empirically model trends (solid line) with 95% confidence interval (dotted lines). NIH (1DP2HD084067; SES); NSF (1454282; SES); ASU Start-up Funds (SES); Ben and Catherine Ivy Foundation (RWS); DoD (W81XWH-14-1-0311; RWS)