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, kb, the rate of degradation–relaxation constant, kr, time to achieve 50% of release, tmax, and effective diffusion coefficient constant (De), 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.
The handling of metallic nanoparticles often requires their dispersion into several polar and nonpolar solvents. Solid-phase stages or polymer-based ligands are commonly required to complete the transfer. The construction of a thiol ligand based in oleic acid, and its ability to efficiently assist in gold and silver nanoparticle aqueous–organic phase transfer is reported. After the transfer, the particles are completely dispersed in an organic solvent, preserving their diameter and morphology, as confirmed by ultraviolet–visible spectroscopy and scanning transmission electron micrographs.
Plasmid DNA (pVAX1-NH36) was encapsulated in nanoparticles of poly-dl-lactic-co-glycolic (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.
The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88) was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1) galactose) was used as the microsphere matrix (MS-Lac) and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3) were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10–17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections.