Paclitaxel-loaded microparticles for intratumoral administration via the TMT technique: preparation, characterization, and preliminary antitumoral evaluation.

Abstract

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.

• Authors: Misara Hamoudeh, Roudayna Diab, Hatem Fessi, Charles Dumontet, Delphine Cuchet
• Journal: Drug development and industrial pharmacy (Drug Dev Ind Pharm) Vol. 34 Issue 7 Pg. 698-707 (Jul 2008) ISSN: 1520-5762 [Electronic] England
• PMID: 18612910 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Delayed-Action Preparations
• Drug Carriers
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Paclitaxel
• Ferrosoferric Oxide

Topics

• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology)
• Calorimetry, Differential Scanning
• Delayed-Action Preparations
• Dose-Response Relationship, Drug
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Female
• Ferrosoferric Oxide (chemistry)
• HeLa Cells
• Humans
• Inhibitory Concentration 50
• Lactic Acid (chemistry)
• Magnetic Resonance Imaging
• Microscopy, Electron, Scanning
• Microspheres
• Paclitaxel (administration & dosage, pharmacology)
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Uterine Cervical Neoplasms (drug therapy)
• X-Ray Diffraction