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Abstract. Biodegradable poly(lactic-co-glycolic acid) copolymer, PLGA nanoparticles (NPs) with a surface layer of poly (ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers, Pluronics, are promising drug carrier systems. With the aim to increase the potential of targeted drug delivery the end group derivative of Pluronics was synthesized in a straightforward way to obtain Pluronic-amines. The formation of functional amine groups was confirmed by fluorescamine method and NMR analysis of their N-(tert-Butoxycarbonyl)-L-phenylalanine (Boc-Phe-OH) and N-(9-Fluorenylmethoxycarbonyl)- L-phenylalanine (Fmoc-Phe-OH) conjugates. Pluronic and Pluronic-amine stabilized PLGA NPs prepared by nanoprecipitation were characterized by dynamic light scattering and zeta potential measurements. All of the systems showed high colloidal stability checked by electrolyte induced aggregation, although the presence of Pluronic-amine on the surface decreased the zeta potential in some extent. The introduction of reactive primary amine groups into the surface layer of PLGA NPs while preserving the aggregation stability, provides a possibility for coupling of various ligands allowing targeted delivery and also contributes to the improved membrane affinity of NPs.
Keywords: biocompatible polymers, Pluronic derivatization, PLGA nanoparticles, colloidal stability, polymeric drug delivery
1. Introduction
Extensive research went into the development of drug delivery systems in the past decades to reduce the side effects and enhance the therapeutic efficacy of drugs [1]. Biodegradable polymeric nanoparticles (NPs) offer the possibility for prolonged drug release as well as targeted delivery. Poly(lactic-co-glycolic acid) copolymers (PLGA) are preferred biomaterials because of their nontoxicity, biocompatibility and biodegradability [2-6]. PLGA readily forms NPs via the nanoprecipitation method as described by Fessi et al. [7]. In most cases the drug is encapsulated into the polymeric particle and released in a controlled way by diffusion and erosion of the polymeric matrix [8-11]. It was found however, that the hydrophobic character of the PLGA triggers the nonspecific adsorption of plasma proteins leading to the uptake of the particles by the mononuclear phagocyte system and hence their fast clearance from the body [12-14]. This undesirable process can be prevented by forming a poly(ethylene oxide), PEO corona on the particle to improve its surface biocompatibility [15-18]. Among the various techniques developed for surface immobilization of PEO the adsorption of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers, the use of Pluronics is a versatile and convenient method to obtain PEO-rich surface on PLGA NPs. The hydrophobic...