Selection and Control of Process Conditions Enable the Preparation of Curcumin-Loaded Poly(lactic- co -glycolic acid) Nanoparticles of Superior Performance.

Curcumin (CUR) is one natural bioactive compound acknowledged for diverse therapeutic activities, but its use is hindered by its poor bioavailability, fast metabolism, and susceptibility to pH variations and light exposure. Thus, the encapsulation in poly(lactic- co -glycolic acid), or PLGA, has been successfully used to protect and enhance CUR absorption in the organism, making CUR-loaded PLGA nanoparticles (NPs) promising drug delivery systems. However, few studies have focused beyond CUR bioavailability, on the environmental variables involved in the encapsulation process, and whether they could help obtain NPs of superior performance. Our study evaluated pH (3.0 or 7.0), temperature (15 or 35 °C), light exposure, and inert atmosphere (N 2 ) incidence in the encapsulation of CUR. The best outcome was at pH 3.0, 15 °C, without light incidence, and without N 2 usage. This best nanoformulation showed NP size, zeta potential, and encapsulation efficiency (EE) of 297 nm, -21 mV, and 72%, respectively. Moreover, the CUR in vitro release at pH values 5.5 and 7.4 suggested different potential applications for these NPs, one of which was demonstrated by the effective inhibition of multiple bacteria ( i.e. , Gram-negative, Gram-positive, and multi-resistant) in the minimal inhibition concentration assay. Besides, statistical analyses confirmed a significant impact of temperature on the NP size; in addition, temperature, light, and N 2 affected the EE of CUR. Thus, the selection and control of process variables resulted in higher CUR encapsulation and customizable outcomes, ultimately enabling more economical processes and providing future scale-up guidelines.