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Sustained release of biologics by poly(lactic-co-glycolic acid) particles and porous contact lenses
Sparks, Zachary
Sparks, Zachary
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2024
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2026-04-04
Abstract
A few decades back, a new class of drugs called biologics started gaining prominence. Biologics are a broad class of drugs which include protein, peptide, and nucleic acid-based therapies. Differences in sizes and stability compared to the small molecule drugs result in different challenges in development of biologics for treating diseases. Biologics are typically not delivered orally like small molecule drugs as they lose efficacy due to enzymes in the gut and have difficulty in passing through the epithelium to reach systemic circulation. Intravenous or subcutaneous injections and transdermal delivery are commonly used. Some challenges of biologic delivery could be addressed by incorporating biologics into biomaterials to improve stability and to sustain release to match the desired pharmacokinetics. This thesis focuses on designing biologic delivery approaches to achieve the desired pharmacokinetics for two applications – delivery of vaccine and delivery of ophthalmic drugs.
As new diseases and new variants of existing diseases arise, there is a need for development of new vaccines as well as improving existing vaccines by modifying formulations and improving delivery to achieve desirable pharmacokinetics with less frequent dosing. This thesis addresses both issues by developing particles for sustained release of influenza virus in combination with natural-killer T cell (NKT) agonist. Biodegradable poly (lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion method to load both NKT agonist α-galactosylceramide (α-GalCer) and the deactivated influenza virus. Particles were developed with >80% encapsulation efficiency and >2 months of release duration.
Ophthalmic drugs are frequently delivered via eye drops despite many deficiencies including rapid clearance from tears which limits bioavailability particularly for large molecular weight biologics. Biologics such as anti-VEGF are delivered via intravitreal injection, i.e., injection directly into the eye. As an alternative, contact lenses were designed to sustain release of biologics to achieve higher permeation in the eye and eliminate invasive injections. Lenses were made with a clear center and porous annulus to load proteins. Lenses were manufactured by a novel approach involving stepwise polymerization in a rotating tube to form a rod. The rod was cut into discs, dried, and lathe-cut into lenses. The approach was successful in manufacturing contact lenses with properties consistent with commercial lenses with the additional feature of loading biologics in the porous annulus, providing sustained release for a few hours.
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