Self-assembled biotransesterified cyclodextrins as potential Artemisinin nanocarriers. II: In vitro behavior toward the immune system and in vivo biodistribution assessment of unloaded nanoparticles.

In a previous study, we reported on the formulation of Artemisinin-loaded surface-decorated nanoparticles (nanospheres and nanoreservoirs) by co-nanoprecipitation of PEG derivatives (PEG1500 and PEG4000-stearate, polysorbate 80) and biosynthesized γ-CD fatty esters. In the present study, the co-nanoprecipitation was extended to the use of a PEGylated phospholipid, namely DMPE-PEG2000. As our goal was to prepare long-circulating nanocarriers for further systemic delivery of Artemisinin (ART), here, we have investigated, on the one hand, the in vitro behavior of these surface-modified γ-CD-C10 particles toward the immune system (complement activation and macrophage uptake assays) and, on the other hand, their biodistribution features in mice. These experiments showed that the in vitro plasma protein adsorption and phagocytosis by macrophage cells triggered by γ-CD-C10 nanoparticles were significantly reduced when their surface was decorated with amphiphilic PEGylated molecules, in particular PEG1500-stearate, DMPE-mPEG2000 or polysorbate 80. The prolonged blood circulation time assessed by fluorescence imaging was demonstrated for unloaded γ-CD-C10-based nanospheres and nanoreservoir particles containing DMPE-PEG2000 and polysorbate80, respectively. These nanoparticles also proved to be non-hemolytic at the concentration range used in vivo. Within the limits of the conducted experiments, the co-nanoprecipitation technique may be considered as an alternative for surface modification of amphiphilic CD-based drug delivery systems and may be applied to the systemic delivery of ART

Colloidal systems made of biotransesterified alpha, beta, and gamma cyclodextrins grafted with C10 alkyl chains

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Size control of amphiphilic cyclodextrin nanoparticles using mixture design methodology

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Miscellaneous nanoaggregates made of β-CD esters synthesised by an enzymatic pathway

International audienceVarious β-cyclodextrin (β-CD) fatty esters with different chain lengths (C4–C14) were synthesised by transesterification of β-cyclodextrin by vinyl fatty ester using thermolysin in DMSO. For each cyclodextrin derivatives, two batches of synthesis were realized. The ability of these derivatives to form nano-organized systems was investigated through the solvent displacement technique. During the formulation step, the effects of the initial concentration of β-CD fatty esters in the organic phase and that of the final volume of the aqueous non-solvent phase were studied. Except for the β-CD C4 ester, the transesterified β-CD derivatives led to measurable nanoparticles. Cryo-electron microscopy images showed a significant morphological variability. Spherical, rod-like or more irregularly-shaped nano-objects were observed with either matricial or lamellar structures. A statistical analysis by a two-way ANOVA was computed for each class of β-cyclodextrin esters in order to determine the effects of batch and formulation on the final size of nanoparticles

Long-term shelf stability of original amphiphilic β-cyclodextrin nanosphere suspensions monitored by dynamic light scattering and cryo-transmission electron microscopy

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Bioesterified polysubstituted-cyclodextrin/surfactant nanoparticles obtained by multilevel self-assembly

The purpose of this work is to investigate the inclusion complexation between a novel amphiphilic biotransesterified cyclodextrin (CD), incorporated in nanostructured environment, and a model drug compound. A water-insoluble γ-cyclodextrin derivative (γ-CD-C10), polysubstituted with multiple (n=7-8) decanoyl chains (C10) on the secondary face, is produced by enzymatically-assisted esterification. The γ-CD-C10 derivative is embedded in amphiphilic nanoenvironment created by self-assembly with the lipophilic dye Nile red (NR) and the non-ionic surfactant polysorbate 80 (P80). The inclusion complexation and the environmental effects upon the γ-CD-C10/NR/P80 nanoparticle (NP) formation, in a multilevel self-assembly approach, are investigated by means of steady-state fluorescence and Förster resonance energy transfer (FRET) techniques. Quasi-elastic light scattering (QELS) is used to control the NP size distribution during the sequential steps of the assembling process

Nanoparticles of β-cyclodextrin esters obtained by self-assembling of biotransesterified β-cyclodextrins

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Progress in developing amphiphilic cyclodextrin-based nanodevices for drug delivery

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Experimental design optimization for screening relvant free phenolic acids from various preparations used in Burkina Faso folk medicine

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