PLA/PLGA nanoparticles for sustained release of docetaxel

This study investigates the potentiality of nanosphere colloidal suspensions as sustained release systems for intravenous administration of
docetaxel (DTX). Nanospheres were prepared by solvent displacement method using polylactic acids (PLA) at different molecular weight and
polylactic-co-glycolic (PLGA) as biodegradable matrices. The systems were characterized by light scattering analysis for their mean size, size
distribution and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The average diameters of the nanoparticles
ranged from 100 to 200 nm. Negative zeta potential values were observed for all systems, particularly the nanospheres produced with the lowest
molecular weight PLA showed a zeta potential value of −28mV. Differential scanning calorimetry analysis (DSC) suggested that DTX was
molecularly dispersed in the polymeric matrices. A biphasic release of DTX was observed for all colloidal suspensions, after a burst effect in
which about 50% (w/w) of the loaded drug was released a sustained release profile for about 10 days was observed. To evaluate the influence
of the polymeric carrier on the interaction of DTX with biological membranes, we performed an in vitro study using lipid vesicles made of
dipalmitoylphosphatidylcholine (DPPC) as a biomembrane model. DSC was used as a simple and not invasive technique of analysis. DTX
produced a depression of DPPC pretransition peak, no variation of the main phase transition temperature and a significative increase of H
value, showing a superficial penetration of the drug into DPPC bilayer. Kinetic experiments demonstrated that the release process of DTX form
nanospheres is affected by the molecular weight of the employed polymers.