title: PLA/PLGA nanoparticles for sustained release of docetaxel.
abstract: 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 DeltaH 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.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Catania, Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Musumeci
authors.forename: C A
authors.initials: CA
authors.lastname: Ventura
authors.forename: I
authors.initials: I
authors.lastname: Giannone
authors.forename: B
authors.initials: B
authors.lastname: Ruozi
authors.forename: L
authors.initials: L
authors.lastname: Montenegro
authors.forename: R
authors.initials: R
authors.lastname: Pignatello
authors.forename: G
authors.initials: G
authors.lastname: Puglisi
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004058:Diffusion; D000077143:Docetaxel; D004339:Drug Compounding; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000737:chemistry*; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D055672:Static Electricity; D013499:Surface Properties; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D008051:Lipid Bilayers; D008081:Liposomes; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D015060:1,2-Dipalmitoylphosphatidylcholine; D019344:Lactic Acid