Track: Formulation and Delivery - Chemical - Formulation - Excipients
Category: Late Breaking Poster Abstract
Biodegradable HydraleseTM (PGSU) (poly(glycerol sebacate) urethane) Microspheres for Controlled Drug Delivery
Purpose: Our team is developing microspheres manufactured from HydraleseTM (PGSU) (poly(glycerol sebacate) urethane), a flexible, synthetic biodegradable elastomer for controlled drug release capable of delivering sustained high drug loadings over a multi-month time period. Hydralese (PGSU) is synthesized by crosslinking poly(glycerol sebacate) (PGS) resin via polyol-isocyanate urethane chemistry and is known to have regenerative and anti-inflammatory properties. Hydralese (PGSU) can achieve steady release of active pharmaceutical ingredients (APIs) from a few weeks to more than a year depending on the crosslinking density and degradation rate. Hydralese (PGSU) degrades by surface erosion, thus maintaining its structure and mechanical strength throughout the duration of its lifespan. Consequently, a drug dispersed in the polymer matrix is released as the polymer matrix erodes, demonstrating that Hydralese (PGSU) can provide long-lasting, zero-order release kinetics for a more controlled drug delivery compared to bulk-eroding polyesters. These unique characteristics make Hydralese (PGSU) an ideal candidate for designing microspheres for steady drug release. The main challenge in developing Hydralese (PGSU) microspheres is timing the reaction between pre-polymer PGS resin and isocyanate as the polymer matrix is shaped into the microsphere. The aims of this study were: 1) to develop drug-loaded Hydralese (PGSU) microspheres by emulsification-solvent evaporation method; 2) to characterize the morphology, chemical structure, and crosslinking density of Hydralese (PGSU) microspheres and evaluate the factors affecting them, and 3) to study the drug release of model API from Hydralese (PGSU) microspheres. Methods: Drug-loaded and unloaded Hydralese (PGSU) microspheres were made by emulsification- solvent evaporation method. The dispersed phase was comprised of the pre-polymer PGS resin, crosslinker isocyanate, and tin catalyst dissolved in an organic solvent. The mass ratio of PGS-to-isocyanate was varied to achieve different crosslinking densities and therefore, different drug release profiles. Model water-soluble and insoluble API powders were dissolved or suspended in the dispersed phase, which was emulsified in oil. This was followed by evaporating the dispersed phase solvent while simultaneously curing Hydralese (PGSU) within the droplet to form microspheres at 60-100℃ for 1-24 hours. The microspheres were washed and dried at 40℃ under vacuum to remove any residual solvents. The time and temperature of curing affected the crosslinking density of the resulting Hydralese (PGSU) microspheres. The size and morphology of the Hydralese (PGSU) microspheres were studied using scanning electron microscopy (SEM). Their chemical structure was characterized by FTIR. Crosslinking density of the PGSU microspheres was determined by swell test in tetrahydrofuran (THF). Drug encapsulation and drug-loading efficiency were calculated and expressed as percentage. Results: Hydralese (PGSU) microspheres were successfully made using emulsification-solvent evaporation method. The reaction between the pre-polymer PGS resin and isocyanate took place in the emulsion droplets forming the PGSU elastomer into a microsphere. This reaction continued during the evaporation step as PGSU was driven to further cure under heat. The time and temperature of the evaporation step affected the crosslinking density of the final product proportionately. Hydralese (PGSU) microspheres were cured to completion by the end of the process. The SEM images show that the microspheres were spherical and had a smooth surface. The chemical structure of Hydralese (PGSU) was confirmed by the amide peaks in FTIR. Hydralese (PGSU) microspheres showed a controlled linear release of the API, with the amount of drug released depending on the crosslinking density of the microspheres. Conclusion: Hydralese (PGSU) microspheres are an excellent alternative to more conventional bulk-eroding polyester microspheres. Their size can be regulated for use in drug delivery or tissue engineering. The crosslinking density can be controlled to achieve the desired drug release profile. As the microspheres degrade and release their drug payload through surface erosion, they retain their flexibility and shape while continuously decreasing in diameter. The degradation products are metabolized by the body and cause no adverse immune reactions, ultimately demonstrating that our biodegradable Hydralese (PGSU) microspheres are an exceptional choice for sustained drug delivery and cell therapy applications.