Smart nanocarriers for pH-triggered targeting and release of hydrophobic drugs

The use of hybrid pH-sensitive micelles mainly based on the PEO129-P2VP43-PCL17 ABC miktoarm star copolymer as potential triggered drug delivery systems has been investigated. Co-micellization of this star copolymer with a second copolymer labeled by a targeting ligand, i.e. biotin, on the pH sensitive block (poly-2-vinylpyridine, P2VP) has been considered here in order to impart possible active targeting of the tumor cells. Two architectures have been studied for these labeled copolymers, i.e. a miktoarm star or a linear ABC terpolymer and the respective hybrid micelles have been compared in terms of cytotoxicity (cells viability) and cellular uptake (by using fluorescent dye loaded micelles). Finally, the triggered drug release in the cytosol of tumor cells was investigated by studying on one hand the lysosomal integrity after internalization and on the other hand the release profile in function of the pH

Effect of various additives and polymers on lysozyme release from PLGA microspheres prepared by an s/o/w emulsion technique

International audienceIncomplete protein release from PLGA-based microspheres due to protein interactions with the polymer is one of the main issues in the development of PLGA protein-loaded microspheres. In this study, a two-dimensional adsorption model was designed to rapidly assess the anti-adsorption effect of formulation components (additives, additives blended with the polymer or modified polymers). Lysozyme was chosen as a model protein because of its strong, non-specific adsorption on the PLGA surface. This study showed that PEGs, poloxamer 188 and BSA totally inhibited protein adsorption onto the PLGA37.5/25 layer. Similarly, it was emphasised that more hydrophilic polymers were less prone to protein adsorption. The correlation between this model and the in vitro release profile was made by microencapsulating lysozyme with a low loading in the presence of these excipients by a non-denaturing s/o/w encapsulation technique. The precipitation of lysozyme with the amphiphilic poloxamer 188 prior to encapsulation exhibited continuous release of active lysozyme over 3 weeks without any burst effect. To promote lysozyme release in the latter stage of release, a PLGA-PEG-PLGA tribloc copolymer was used; lysozyme was continuously released over 45 days in a biologically active form