(630e) The Additives to PLGA Nanoparticles – Influence of the Glass Transition Temperature on Drug Release Behavior

Poly(D,L-lactic-co-glycolic acid) (PLGA) is a commonly used drug carrier in nanomedicines, owing to its low toxicity, biodegradability, and biocompatibility. In practice, PLGA particles protect the drugs from enzymatic reactions, ensuring the desired release profile. The particles' size adjustability facilitates their transportation through cell membrane barriers, and various preparation methods and surface modifications enhance their specificity to target particular organs, tissues, and cells, while minimizing toxicity at non-target sites. Typically, the characterization of PLGA nanoparticles involves determining their particle diameter, size distribution, morphology, and surface charge. However, the significance of the glass transition temperature (T_g) of nanoparticles in an aqueous dispersion is often overlooked, despite T_g being an important parameter of the drug loaded PLGA nanoparticles.

In this study, we aim to examine the impact of T_g of PLGA nanoparticles in two aspects: surfactant and loaded drug. To minimize the T_g increase from a secondary component in the particle matrix, we have opted for a non-polymeric surfactant, didodecyl dimethyl ammonium bromide (DMAB), as an alternative stabilizer during PLGA nanoparticle preparation, and compared its efficacy with that of the commonly used surfactant, polyvinyl alcohol (PVA). Our results showed that the T_g of both PVA and DMAB stabilized particle and bulk samples measured in wet conditions is significantly lower compared to that in dry conditions when residual surfactant is present, except for bulk PLGA containing DMAB. This observation may be attributed to the plasticizing effect of small surfactant molecules. Importantly, the T_g of particles in wet conditions is approaching physiological temperatures, where even minor variations in T_g could have a significant impact on drug release behaviors.

Additionally, flurbiprofen (FBP) was used as a model drug to investigate its plasticizing effect on PLGA nanoparticles. Our finding indicates that an increased drug loading efficiency of PLGA nanoparticles leads to reduction in T_g of the nanoparticles, which is in agreement with previous studies. Results from a release study of FBP-loaded PLGA particles will also be presented.