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 1:1 weight ratio between GE11-PLGA and PEG-PLGA, obtaining smart nanoplatforms with proper size for parenteral administration (143.9 ± 5.0 nm). 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 60 days. GE11-PLGA/PEG-PLGA blend nanoparticles showed good in vitro stability for 30 days in physiological saline solution at 4 °C and for 24 h in pH 7.4 or pH 5.0 buffer at 37 °C 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 4 h. 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.
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 / B. Colzani, G. Speranza, R. Dorati, B. Conti, T. Modena, G. Bruni, E. Zagato, L. Vermeulen, G.R. Dakwar, K. Braeckmans, I. Genta. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - 511:2(2016 Sep 25), pp. 1112-1123.
|Titolo:||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|
SPERANZA, GIOVANNA (Secondo)
|Parole Chiave:||EGFR-targeted nanoparticles; GE11 peptide; GE11 targeted PLGA nanoplatforms; macromolecular hydrophilic drugs nanoencapsulation; smart PLGA nanoparticles; 3003|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
Settore CHIM/08 - Chimica Farmaceutica
|Data di pubblicazione:||25-set-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.ijpharm.2016.08.011|
|Appare nelle tipologie:||01 - Articolo su periodico|