PLGA:Poloxamer and PLGA:Poloxamine Blend Nanoparticles:  New Carriers for Gene Delivery

Abstract

The main objective of the present work was the development of new nanoparticulate carrier systems for the delivery of plasmid DNA. These new carriers consist of a blend matrix formed by a poly(lactic-co-glycolic acid) (PLGA) copolymer and polyoxyethylene derivatives. More specifically, we have prepared nanostructures with different PLGA:poloxamer and PLGA:poloxamine compositions by an optimized emulsification-solvent diffusion technique and studied the potential of these carriers for the encapsulation and controlled release of plasmid DNA. Depending on the particle composition, the encapsulation efficiency of the model plasmid pEGFP-C1 varied between 30% and 45%. All formulations provided continuous and controlled release of the plasmid with minimal burst effect. In addition, the release rate and duration was dependent on the composition of the particle matrix. Moreover, gel electrophoresis and cell culture (MCF-7 cell line) assays allowed us to confirm that the biologically active form of the plasmid was preserved during the particle preparation process and also during its release. Cell culture experiments also indicated that the new nanoparticles do not exhibit toxic effects on these cells at concentrations up to 5 mg/mL. Altogether, these results indicate that these composite nanostructures present a promising approach for the delivery of plasmid DNA.

Poly(Ethylene Oxide)-Modified Poly(β-Amino Ester) Nanoparticles as a pH-Sensitive System for Tumor-Targeted Delivery of Hydrophobic Drugs: Part 2. In Vivo Distribution and Tumor Localization Studies

“…Majority of reported strategies employ poly(ethylene glycol) (PEG) or poly(ethylene oxide) (PEO) chains for surface modification through physical adsorption during particle formation or by covalent linkage to the core-forming polymer [e.g., copolymer of PEG/PEO with poly(lactic acid)] prior to particle formation (19,(36)(37)(38)(39)(40)(41). More recently, the possibility of introducing PEOcontaining block copolymers into the nanoparticles matrix has been achieved by intimate blending of the PEO-copolymer with the core-forming polymer prior to nanoparticulate fabrication (42,43). This method of PEO incorporation is expected to lead to partitioning of the PEO chains on the nanoparticle surface upon hydration and better stability of the PEO chains on the nanoparticle surface.…”

Surfactant−DNA Gel Particles: Formation and Release Characteristics

“…For this purpose, poly(lactic-coglycolic acid) (PLGA) microspheres have been used. [14][15][16] However, the problems encountered in reaching this goal were related not only to the microencapsulation technologies but also to the intrinsic nature of polyesters. Indeed, the PLGA microencapsulation technologies imply the use of organic solvents and high energy sources, thus leading to a significant degradation of the encapsulated macromolecule during the course of the PLGA hydrolysis.…”

Poly (D,L-lactide-co-glycolide) nanoparticles: Uptake by epithelial cells and cytotoxicity

“…Team work previously conducted on similar PLGA nanoparticles used in this study showed that PLGA nanoparticles with an average size of 300 nm had no detrimental effects on mammalian cells including Caco-2 cells up to a concentration range of 0.001 mg/mL [32]. Particles prepared by the emulsion solvent evaporation technique were not toxic to human glioblastoma U87MG cells at 200 &g/mL [43] or mammalian cells [44,45]. This study showed that PLGA nanoparticles are not toxic to Caco-2 cells even at relatively high concentrations, which have not been evaluated before.…”