Formulation of sustained release nanoparticles loaded with a tripentone, a new anticancer agent

• Published in: International journal of pharmaceutics 2006-08, Vol.320 (1), p.157-164
• Main Authors: Malzert-Fréon, A., Vrignaud, S., Saulnier, P., Lisowski, V., Benoît, J.P., Rault, S.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Colloids; Cytotoxic activity; Delayed-Action Preparations; Drug Carriers; Feasibility Studies; General pharmacology; Inhibitory Concentration 50; Interfacial tension measurements; Lipid nanoparticles; Medical sciences; Mice; Nanoparticles; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Pyrrolizidine Alkaloids - chemistry; Pyrrolizidine Alkaloids - pharmacology; Rheology; Solubility; Stearic Acids - chemistry; Surface Tension; Time Factors; Triglycerides - chemistry; Tripentones; Tubulin Modulators - chemistry; Tubulin Modulators - pharmacology
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2006.04.007

The purpose of the present work is to develop nanoparticles of a new antitubulin agent of the family of tripentones by means of a phase inversion process. Dynamic light scattering, transmission electron microscopy and ζ-potential measurements were used to characterize tripentone loaded nanoparticles. From interfacial tension measurements and from the study of the rheological interfacial properties of the tripentone at the Labrafac ®–Solutol ® interface, the fraction of tripentone initially present in Labrafac ® would stay in the oily core of nanocapsules. Moreover, the interpenetration of some tripentone molecules within the surfactant units helps to the stabilization of the formulated nanoparticles. The encapsulation efficiency was determined by high performance liquid chromatography (HPLC) and was found to be above 95%. In vitro release studies were carried out in blank nanoparticles containing phosphate buffer, pH 7.4, at 37 °C. The drug release kinetics was measured by HPLC. Antiproliferative activity studies on L1210 cells showed that the cytotoxic activity of tripentone was totally recovered after encapsulation of the antitubulin agent in lipid nanoparticles. This study shows that lipid nanocapsules could be a promising and effective carrier for tripentone delivery in the treatment of cancers.