(671g) Glass Transition Temperature in PLGA Nanoparticles

Since poly(lactic-co-glycolic acid) has been approved by U.S. FDA (Food and Drug Administration) in 1989, more than 20 PLGA formulations are available on the market in 30 years development. In application, PLGA particles protect the loaded drugs from enzymatic reactions to reach a designed release profile. The tunable size of the PLGA particles enhances the transport through cell membrane barriers. Diverse preparation methods and surface modifications improve PLGA particles specificity to reach the targeted organ, tissue, and cells, which minimizes the toxicity at other sites. Many researchers investigated the influence of particle size, polydispersity index (PDI), surface morphology, zeta potential, and drug loading efficiency on drug release behavior. Glass transition temperature (Tg) of PLGA particles, on the other hand, is an underreported property of current PLGA based drug delivery systems.

Studies showed that, even after purification, a small amount of residual polyvinyl alcohol (PVA), a common surfactant during particle synthesis, remains in the PLGA nanoparticle matrix. This residual PVA can be attached to the particle surface or remain inside the particle itself, and its weight percentage can be as high as 13 wt%. The surface attached surfactant is going to change the hydrophilicity of the particle thus leading to different cellular uptake. Therefore, measuring the residual surfactant is important in drug delivery of PLGA particles. Herein, we proposed a novel method to evaluate the remaining PVA by TMDSC (temperature modulated differential scanning calorimetry). According to our findings, nanoprecipitation PLGA nanoparticles had a residual PVA content of 8% ~ 12%, while particles prepared by nanoemulsion had between 6% to 10%. Results from ¹H nuclear magnetic resonance spectroscopy (NMR) and UV/Vis spectroscopy will also be presented.

Furthermore, we selected the non-polymeric surfactant didodecyl dimethyl ammonium bromide (DMAB) as alternative stabilizer in PLGA nanoparticle preparation in order to minimize the Tg increase from a second component in the particle matrix. Our results showed that Tg of DMAB-PLGA NPs is higher than that of bulk, which is in contrast to previous investigations of PS nanoparticles in confinement, suggesting the role of surfactant and interfaces in the Tg of PLGA particles may differ from that of PS.