Design of smart GE11 PLGA/PEG PLGA blend nanoparticulate platforms for parenteral administration of hydrophilic macromolecular drugs: synthesis, preparation and in vitro/ex vivo characterization.
Active drug targeting and controlled release of hydrophilic macromolecular drugs represent crucial points in designing efficient polymeric drug delivery nanoplatforms. In the present work EGFR targeted polylactide co glycolide (PLGA) nanoparticles were made by a blend of two different PLGA based polymers. The first, GE11 PLGA, in which PLGA was functionalized with GE11, a small peptide and EGFR allosteric ligand, able to give nanoparticles selective targeting features. The second polymer was a PEGylated PLGA (PEG PLGA) aimed at improving nanoparticles hydrophilicity and stealth features. GE11 and GE11 PLGA were custom synthetized through a simple and inexpensive method. The nanoprecipitation technique was exploited for the preparation of polymeric nanoparticles composed by a 1:1weight ratio between GE11 PLGA and PEG PLGA, obtaining smart nanoplatforms with proper size for parenteral administration (143.9+ 5.0nm) In vitro cellular uptake in EGFR overexpressing cell line (A549) demonstrated an active internalization of GE11 functionalized nanoparticles. GE11 PLGA/PEG PLGA blend nanoparticles were loaded with Myoglobin, a model hydrophilic macromolecule, reaching a good loading (2.42% respect to the theoretical 4.00% w/w) and a prolonged release over 60days. GE11 PLGA/PEG PLGA blend nanoparticles showed good in vitro stability for 30days in physiological saline solution at 4degC and for 24h in pH 7.4 or pH 5.0 buffer at 37degC respectively, giving indications about potential storage and administration conditions. Furthermore ex vivo stability study in human plasma using fluorescence Single Particle Tracking (fSPT) assessed good GE11 PLGA/PEG PLGA nanoparticles dimensional stability after 1 and 4h. Thanks to the versatility in polymeric composition and relative tunable nanoparticles features in terms of drug incorporation and release, GE11 PLGA/PEG PLGA blend NPs can be considered highly promising as smart nanoparticulate platforms for the treatment of diseases characterized by EGFR overexpression by parenteral administration
International journal of pharmaceutics