Paclitaxel-loaded microparticles for intratumoral administration via the TMT technique: preparation, characterization, and preliminary antitumoral evaluation.
In our pursuit to develop suitable therapeutic particulate systems for intratumoral delivery by the targeted multi-therapy (TMT) technique, we describe the preparation of paclitaxel-loaded poly(D,L-lactic-co-glycolic) acid (PLGA) microparticles (MPs) (drug loading 35-38%, wt/wt; size 0.7-5 microm). Magnetite (15%, wt/wt) was also incorporated in some preparations for a future magnetic resonance imaging (MRI)-guided delivery. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) experiments showed that paclitaxel was not encapsulated in its initial crystalline form. The paclitaxel in vitro release pattern showed a biphasic tendency with a burst effect followed by a sustained release (28% released amount after 1 month), which was accompanied with MP erosion and degradation signs as confirmed by scanning electronic microscopy (SEM) micrographs. The paclitaxel-loaded MPs demonstrated a dose-dependent antitumor effect on human uterine cancer cells, with an IC(50) value relatively close to that of commercial Taxol. This paclitaxel delivery system represents a potent antiprofilerative and radiosensitizer agent for intratumoral administration via the TMT technique.
Hamoudeh
Misara
M
Pharmaceutics and Pharmaceutical Technology Department, LAGEP, Laboratoire d'Automatique et de Genie de Procedes, UMR CNRS, Universite Claude Bernard Lyon1, CPE-Lyon, Villeurbanne, France.
Diab
Roudayna
R
Fessi
Hatem
H
Dumontet
Charles
C
Cuchet
Delphine
D
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D019344:Lactic Acid / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D014961:X-Ray Diffraction
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel; D052203:Ferrosoferric Oxide