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Title: Nanoparticle Encapsulation of Macromolecular Biologics by Hydrophobic Ion Pairing Flash NanoPrecipitation (HIP-FNP)
Authors: Rummaneethorn, Joe
Advisors: Prud'homme, Robert K
Department: Chemical and Biological Engineering
Certificate Program: Engineering Biology Program
Class Year: 2018
Abstract: Therapeutic biologics have garnered significant market in the pharmaceutical industry recently due to their therapeutic efficacy, derived their complex structures, which outclasses many small molecule drugs. However, delivery remains a challenge due to physiological challenges such as immune system detection and fast renal clearance. The structural complexity of biologics has posed difficulties for encapsulation in nanocarriers due to susceptible to loss of structural integrity and hence therapeutic efficacy under process conditions such as organic solvent exposure and sonication. Current available techniques that have successfully encapsulated biologics, such as liposomes, have suffered from low encapsulation efficiency and loading. Hydrophobic ion pairing (HIP) complexation has been used to successfully encapsulate lysozyme, a model protein, into nanoparticles with ion pairing reagents (IP) sodium dodecyl sulfate (SDS), sodium oleate (OA), and dextran sulfate sodium salt (DS). However, these techniques have also suffered from low encapsulation efficiency, low loading, and/or large particle sizes. Here we present a new nanoparticle (NP) fabrication technique that combines HIP complexation chemistry with Flash NanoPrecipitation (FNP)—HIP-FNP—for nanoparticle encapsulation of macromolecular biologics using lysozyme as a starting model. We studied the HIP complexation of lysozyme with SDS, OA, and DS under different pH and lysozyme:IP charge ratio conditions, and present three HIP-FNP methods for NP fabrication. Results of the study indicated NPs fabricated by HIP-FNP exhibit desirable size range (50-150nm) with narrow size distributions (PDI ~ 0.2), high encapsulation efficiency (90-100%), high lysozyme mass loading (30-50%), stability in water after 72 hours, and tunable release rates (5-50% lysozyme released after 14 days) by varying IP and charge ratios. Bioactivity of lysozyme was retained up to 100% after release. HIP-FNP presents a technique that is therapeutically and economically for industrial scale-up processing of biologics-encapsulated NP production.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Chemical and Biological Engineering, 1931-2018

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