title: Formulation of sustained release nanoparticles loaded with a tripentone, a new anticancer agent.
abstract: 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 zeta-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 degrees 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.
authors.affiliation: Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA 3915, Département de Pharmacie Galénique, 5 rue Vaubénard, 14032 Caen Cedex, France. aurelie.malzert-freon@unicaen.fr
authors.forename: A
authors.initials: A
authors.lastname: Malzert-Fréon
authors.forename: S
authors.initials: S
authors.lastname: Vrignaud
authors.forename: P
authors.initials: P
authors.lastname: Saulnier
authors.forename: V
authors.initials: V
authors.lastname: Lisowski
authors.forename: J P
authors.initials: JP
authors.lastname: Benoît
authors.forename: S
authors.initials: S
authors.lastname: Rault
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003102:Colloids; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005240:Feasibility Studies; D020128:Inhibitory Concentration 50; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D012212:Rheology; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D013500:Surface Tension; D013997:Time Factors; D014280:Triglycerides / Q000737:chemistry; D050257:Tubulin Modulators / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C483893:3-(3-hydroxy-4-methoxyphenyl)-8H-thieno(2,3-b)pyrrolizin-8-one; D000970:Antineoplastic Agents; D003102:Colloids; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011763:Pyrrolizidine Alkaloids; D013229:Stearic Acids; D014280:Triglycerides; D050257:Tubulin Modulators; D011092:Polyethylene Glycols; C067028:Solutol HS 15