PEGylated Degradable Composite Nanoparticles Based on Mixtures of PEG-b-Poly(γ-benzyl l-glutamate) and Poly(γ-benzyl l-glutamate)

Abstract

In the present work, the possibility to obtain PEGylated nanoparticles from two PBLG derivatives, PEG-b-poly(γ-benzyl L-glutamate), PBLG-PEG-60, and poly(γ-benzyl L-glutamate), PBLG-Bnz-50, by nanoprecipitation has been investigated. Particles were prepared not only from one polymer (PBLG-PEG-60 or PBLG-Bnz-50), but also from mixtures of two PBLG derivatives, PBLG-PEG-60 and PBLG-Bnz-50, in different ratios (90/10, 77/23, and 40/60 wt %). Because of the presence of PEG chains, hydrophilic particles were obtained, which was confirmed by ζ potential measurements (ζ from -13 mV and -21 mV) and by isothermal titration microcalorimetry (ITC). This last technique has shown no heat exchange when BSA was added to PEGylated nanoparticles. Further, complement activation has been evaluated by crossed immuno-electrophoresis demonstrating that the introduction of 77 wt % of PEGylated PBLG chains in the particles was enough to ensure a low complement activation activity. This effect was strongly correlated to the ζ potential of the particles, which decreased with an increase of PEG chains content. Interestingly, such properties are of interest for the preparation of degradable stealth nanocarriers. Moreover, it is suggested that the introduction of a reasonable amount (up to 20 wt %) of a second copolymer in the particle composition can be possible without modifying their stealth character. Moreover, the presence of this second copolymer would help to introduce a second functionality to the particles.

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

“…This absence of segregation could be attributed to the similarity of the PBLG segment in these copolymers. Further, it was shown that the incorporation of 77% of PBLG-PEG copolymer chains in the nanoparticles was enough to maintain the "stealthiness" of the particles, as suggested by ITC adsorption and complementary activation measurements of Martinez-Barbosa et al 28 Thus, in the present experiment, an amount of 20% (w/w) of PBLG-FITC was considered to be a good compromise for ensuring stealth properties in the body and simultaneously an optimal fluorescence labeling.…”

“…ITC analysis was performed to investigate the efficiency of PEG chains to reduce interactions with proteins because of the hydrophilization of the surface of the particles and steric repulsions. As shown earlier by Martinez-Barbosa et al, 28 ITC can be conveniently used for investigating this effect. In the present study, BSA was used for probing the capacity of PBLG nanoparticles to avoid interactions with proteins.…”

“…The aim of this study was to investigate the biodistribution and efficacy of the pegylation of recently developed multifunctional PBLG nanoparticles. 2,27,28 For this purpose, nanoparticles were prepared by a nanoprecipitation method using mixtures of different PBLG derivates, including a pegylated derivate, to avoid MPS uptake. Further, their distribution in tissues were investigated using fluorescein isothiocyanate (FITC) derivate-tagged nanoparticles after IV administration in rats, with a specific emphasis on their affinity for liver and spleen tissues, known as the major organs involved in the capture of nanoparticles in vivo.…”

Nanomaterials: Applications in Drug Delivery

“…Nanomaterials therefore need to be engineered according to their biological fate and associated therapeutic challenges. In general, morphology, shape, structure, and size of nanomaterials are set during their preparation [36,77,115]. Drug loading occurs preferentially during preparation but in some cases, the drug can only be associated on preformed nanomaterials [33,36,115].…”

“…5.1). Polymer-based nanomaterials with non-spherical shapes are also currently investigated [38,77,118]. Carbon-based materials were recently introduced as potential nanomaterials to improve the delivery of drugs in vivo.…”