Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process

This study presents a new groundbreaking methodology for integrating innovative concepts todevelop novel drug-delivery strategies. This methodology combines genetically engineered elastin-likerecombinamers (ELRs) with supercritical fluid (SCF) techniques to encapsulate a poorly water-solubledrug in a one-step process. The chemotherapeutic agent docetaxel (DTX) is encapsulated with a blockcopolymer ELR containing the RGD peptide, a specific target sequence for cancer cells, using thesupercritical anti-solvent (SAS) technique in a high process yield of up to 70%. SEM studies showspherical microparticles of 10 mm after encapsulation. After dispersion under physiological conditions,microparticles disaggregate into stable monodisperse nanoparticles of 40 nm size and 30 mVz-potential. This protects the drug, as confirmed by NMR analysis, thereby increasing the watersolubility of DTX up to fifty orders of magnitude. The delivery process is governed by the Fick diffusionmechanism and indicates that the presence of DTX on the particles surface is practically negligible.Cellular assays showed that, due to the presence of the cancer target sequence RGD, breast cancer cellswere more affected than human endothelial cells, thus meaning that the strategy developed in thiswork opens the way to new controlled release systems more precise than non-selectivechemotherapeutic drugs.
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