Pegylation of poly(γ-benzyl-L-glutamate) nanoparticles is efficient for avoiding mononuclear phagocyte system capture in rats

Abstract

Poly(γ-benzyl-L-glutamate) (PBLG) derivatives are synthetic polypeptides for preparing nanoparticles with well controlled surface properties. The aim of this paper was to investigate the biodistribution of pegylated PBLG in rats. For this purpose, nanoparticles were prepared by a nanoprecipitation method using mixtures of different PBLG derivates, including a pegylated derivate to avoid mononuclear phagocyte system uptake. The morphology, size distribution, and surface charge of the nanoparticles were investigated as a function of the amount of polymer employed for the preparation. Moderately polydispersed nanoparticles (polydispersity index less than 0.2) were obtained. Their size increased with polymer concentration. The zeta potential values were negative whatever the formulations. The availability of polyethylene glycol chains on the nanoparticles' surface was confirmed by measuring the decrease in bovine serum albumin adsorption. For in vivo distribution studies, pegylated and nonpegylated nanoparticles were prepared with polymer mixtures containing PBLG-fluorescein isothiocyanate and imaged by fluorescence microscopy to measure their accumulation in liver and spleen tissues of rats after intravenous administration. Injection of stealth formulations resulted in negligible fluorescence in liver and spleen compared with nonpegylated formulations, which suggests that these nanoparticles are promising candidates as a stealth-type long-circulating drug carrier system and could be useful for active targeting of drugs while reducing systemic side effects.

Cellular delivery of PEGylated PLGA nanoparticles

“…One approach in overcoming this problem is to increase the hydrophilicity of the particle surface. The presence of hydrophilic polymer on the surface can protect nanoparticles from capture by macrophages [5,6] . Hydrophilic polymer on the surface also improves cytoplasmic transfer of particles, [7] and reduces enzymatic degradation [8] .…”

“…The presence of hydrophilic polymer on the surface can protect nanoparticles from capture by macrophages. [5,6] Hydrophilic polymer on the surface also improves cytoplasmic transfer of particles, [7] and reduces enzymatic degradation. [8] Recent reports demonstrate that the rapid RES uptake of PLGA nanoparticles could be significantly reduced by modifying their surface with polyethylene glycol (PEG).…”

Synthesis and characterization of surface‐modified PBLG nanoparticles for bone targeting: In vitro and in vivo evaluations

“…According to the previous work, the effective FITC concentration for in vivo imaging studies of NPs in tissues was found as 20 wt % 40. The in vivo binding of the prepared NP formulations at this ratio to bone was shown in Figure 7.…”

Amphiphilic PEO‐b‐PBLG Diblock and PBLG‐b‐PEO‐b‐PBLG Triblock Copolymer Based Nanoparticles: Doxorubicin Loading and In Vitro Evaluation

“…PBLG, a synthetic polypeptide, is particularly interesting because its ability to form secondary structures such as α‐helices or β‐strands, which has been shown to be important to drive NPs formation . Moreover, PBLG is a biocompatible polymer easy to modify with various chemical moieties . PEO, also often referred as poly(ethylene glycol) (PEG), is often preferred as the hydrophilic segment by virtue of its biocompatibility, safety, non‐immunogenic and non‐antigenic properties, high solubility in water, and ability to escape the mononuclear phagocyte system (MPS), which prevents preliminary elimination of the NPs from the blood stream .…”