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Title: Optimization of Workup for Nanoparticle Incorporation into PLGA Microparticles: Novel Delivery Platform for Biologic Therapies
Authors: Robertson-Lavalle, Sophia
Advisors: Prud'homme, Robert K.
Department: Chemical and Biological Engineering
Class Year: 2016
Abstract: Protein and peptide therapeutics, also known as biologics, hold much promise in the prevention and treatment of diseases. Their specificity and potency set them apart from conventional small molecule drugs. However, the same structural complexity that leads to these favorable characteristics also creates significant challenges in formulation and delivery. Given a number of complications related to oral delivery, most biologics to date are delivered through injection. Unfortunately, this comes at the price of short drug half lives, the need for frequent dosing, and low patient compliance. A significant amount of research has been conducted to develop a parenteral delivery system that achieves high drug loading and controlled long-term release. Recently, a potential solution was proposed: nanoparticle (NP) embedded PLGA microparticles (MPs). NPs containing biologics are formed using inverted Flash NanoPrecipitation. The resulting stable and highly loaded dispersion undergoes a workup to be incorporated into PLGA MPs, via an oil-in-water emulsion. The final particle can be injected as a depot delivery system which releases the drug over periods of weeks or months. In this work, we present an optimized NP workup that improves reproducibility, scalability, and efficiency. We show that through the elimination of a precipitation step in the workup for NP incorporation into MPs, we not only achieve reproducibility, but also enable controlled release. This is because precipitation causes irreversible NP aggregation that presumably leads to variable dosage release from the final MP. Our work demonstrates that NPs produced via this optimized workup are successfully incorporated into PLGA MPs. By using dyes and fluorescently tagged biologics, we show that NPs are evenly distributed throughout the final MP, which we believe will lead to controlled drug release. Overall, this work represents a significant improvement in the groundwork for NP incorporation into PLGA MPs, a novel delivery platform for biologic therapies.
Extent: 72 pages
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Chemical and Biological Engineering, 1931-2017

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