Limited control of drug release of commonly used poly(lactide-co-glycolide) (PLGA) and poly(lactic acid) (PLA) microparticles has led to the investigation of a tyrosine-derived polymer library with varying structure-property relationships that has the capability to control drug release rates from microparticles. A microparticle preparation method has been optimized using a continuous flow method to prepare particles ranging from 100-130 µm in size loaded with both hydrophilic and hydrophobic drugs. This delivery system allows for localized delivery of a wide range of therapeutic drugs. A thorough investigation into how polymer structure-property relationships effect drug encapsulation and release has been performed evaluating the tyrosol-derived polymer library against PLGA and PLA. The tyrosol-derived polymer library is an alternating AB polymer system with A either tyrosol or desaminotyrosine and B a diacid of varying carbon length. High encapsulation of a hydrophobic drug, dexamethasone, was achieved for all formulations prepared and all formed a miscible drug-polymer interface at 20% w/w loading which is key to achieving a controlled release system. PLGA and PLA exhibited 43% and 24% cumulative release respectively after 41 days, while tyrosol-derived polymers exhibited between 37-65% cumulative release depending on the polymer. By selecting a polymer with certain structure-property relationships, such as polymer hydrophobicity and mixed T<sub>g</sub> (polymer-drug) it is possible to directly control the release profile. Incorporation of drug at multiple loadings predicts the mixed T<sub>g</sub> and determines when the polymer-drug is no longer miscible, which has shown to correlate with release rates. Ongoing studies are using polymers containing polyethylene glycol in the polymer backbone as an attempt to obtain a faster releasing particle system.

Controlled Drug Release by Varying Polymer Structure-Property Relationships in Microparticles

ACS Fall 2020 Virtual Meeting

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