This study presents the influence of the primary formulation parameters on the formation of poly-dl-lactic-co-glycolic nanoparticles by the emulsification-solvent evaporation, and the nanoprecipitation techniques.

In this study we describe a mathematical analysis that considers the temperature effects of the controlled drug release process from biodegradable poly-D,L-lactide-co-glycolide (PLGA) nanoparticles.Temperature effects are incorporated and applied to two drug release models. The first one consists of a two-stage release process that considers only simultaneous contributions of initial burst and nanoparticle degradation-relaxation (BR model). The second one is a three release stage model that considers, additionally, a simultaneous drug diffusion (BRD model) step. In these models, the temperature dependency of the release parameters, initial burst constant, k b , the rate of degradationrelaxation constant, k r , time to achieve 50% of release, t max , and effective diffusion coefficient constant (D e ), are determined using mathematical expressions analogous to the Arrhenius equation. The temperature dependent models are used to analyze the release of previously encapsulated Rhodamine 6G dye as a model drug in polyethylene glycol modified PLGA nanoparticles. The experimental data used to develop the mathematical model was obtained from release studies carried out in phosphate buffer pH 7.4 at 37 C, 47 C, and 57 C. Multiphasic release behaviors with an overall increase rate associated with the incubation temperature were observed. The study incorporates a parametrical analysis that can evaluate diverse temperature variation effects of the controlled release parameters for the two models.

Plasmid DNA (pVAX1-NH36) was encapsulated in nanoparticles of poly-dl-lactic-coglycolic (PLGA) functionalized with polyethylene glycol (PEG) and folic acid (PLGA-PEG-FA) without losing integrity. PLGA-PEG-FA nanoparticles loaded with pVAX1-NH36 (pDNA-NPs) were prepared by using a double emulsification-solvent evaporation technique. PLGA-PEG-FA synthesis was verified by FT-IR and spectrophotometry methods. pVAX1-NH36 was replicated in Escherichia coli (E. coli) cell cultures. Atomic force microscopy (AFM) analysis confirmed pDNA-NPs size with an average diameter of 177-229 nm, depending on pVAX1-NH36 loading and zeta potentials were below −24 mV for all preparations. In vitro release studies confirmed a multiphase release profile for the duration of more than 30-days. Plasmid release kinetics were analyzed with a release model that considered simultaneous contributions of initial burst and degradation-relaxation of nanoparticles. Fitting of release model against experimental data presented excellent correlation. This mathematical analysis presents a novel approach to describe and predict the release of plasmid DNA from biodegradable nanoparticles.