Polymeric nanoparticles, such as poly (lactide-co-glycolic acid) (PLGA) and polylactide acid (PLA), have been widely developed as drug delivery systems in the past few decades. PLGA and PLA are frequently used for their biocompatibility, nontoxicity, and biodegradation. There are many factors such as particle size, drug solubility, polymer biodegradation and diffusion, that could influence the drug release rate and efficiency of the drug delivery system. One of the concerning issues with these particles is residual surfactant used in the particle synthesis. Surfactants are often toxic, can change the ability of cells to uptake the particles, and can change the properties of the particles. Polyvinyl alcohol (PVA) is a common emulsifier in preparation of PLGA nanoparticles, and previous studies have shown a fraction of residual PVA remained with the nanoparticle despite the purification procedure. This fraction of PVA could potentially be up to 13wt% and could be attached on the particle surface or remain inside the particle. PVA on the particle surface will have a significant influence on the physical and pharmaceutical properties of the particles. In previous work, even a small amount of substance between a polymer particle and liquid interface has a dramatic impact on glass transition temperature (Tg) when measured in the liquid phase. A dramatic change in the Tg would influence the drug release profile as the effects of burst release are greater the closer to Tg the polymer particle is. In the case of PLGA with a bulk Tg around 40°C, even a slight change in Tg could have a profound effect on the drug release profile. Therefore, evaluation of residual surfactant and the resulting Tg is important in polymeric nanoparticle study.
The quantification of residual PVA in PLGA nanoparticles is often characterized by UV/vis spectroscopy, or occasionally by 1H nuclear magnetic resonance spectroscopy (NMR). However, a few limitations in these methods make them more complicated or unavailable for certain samples. Therefore, we propose a novel method to quantitatively measure the residual PVA in PLGA nanoparticles by using temperature modulated differential scanning calorimetry (TMDSC) to measure the shift in Tg caused by the presence of residual PVA. Residual surfactant determination by TMDSC is a more accurate measurement and improves sensitivity to detect weak transitions, and more importantly, it is a one-step approach to evaluate thermal properties and the presence of residual surfactant simultaneously. Our results suggest that the residual PVA in PLGA nanoparticles prepared by nanoprecipitation ranged from 15% to 16%, which is slightly higher than previously reported data.
