title: Oil-in-water biocompatible microemulsion as a carrier for the antitumor drug compound methyl dihydrojasmonate.
abstract: Methyl dihydrojasmonate (MJ) has been studied because of its application as an antitumor drug compound. However, as MJ is a poorly water-soluble compound, a suitable oil-in-water microemulsion (ME) has been studied in order to provide its solubilization in an aqueous media and to allow its administration by the parenteral route. The ME used in this work was characterized on the pseudo-ternary phase diagram by dynamic light scattering and rheological measurements. Regardless of the drug presence, the droplet size was directly dependent on the oil/surfactant (O/S) ratio. Furthermore, the drug incorporation into the ME significantly increased the ME diameter, mainly at low O/S ratios. The rheological evaluation of the systems showed that in the absence of drug a Newtonian behavior was observed. On the other hand, in the presence of MJ the ME systems revealed pseudoplastic behavior, independently of the O/S ratio. The in vivo studies demonstrated that not only was the effect on the tumor inhibition inversely dependent on the MJ-loaded ME administered dose, but also it was slightly higher than the doxorubicin alone, which was used as the positive control. Additionally, a small antiangiogenic effect for MJ-loaded ME was found at doses in which it possesses antitumor activity. MJ revealed to be nontoxic at doses higher than 350 mg/kg, which was higher than the dose that provides tumor-inhibition effect in this study. Because the MJ-loaded ME was shown to have anticancer activity comparable to doxorubicin, the ME described here may be considered a suitable vehicle for parenteral administration of MJ.
authors.affiliation: Departamento de Fármacos e Medicamentos, UNESP-Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, PPG em Nanotecnologia Farmacêutica, Rodovia Araraquara-Jaú Km 01, Araraquara, SP, Brazil.
authors.forename: Gisela Bevilacqua Rolfsen Ferreira
authors.initials: GB
authors.lastname: da Silva
authors.affiliation: Departamento de Fármacos e Medicamentos, UNESP-Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, PPG em Nanotecnologia Farmacêutica, Rodovia Araraquara-Jaú Km 01, Araraquara, SP, Brazil.
authors.forename: Maria Virginia
authors.initials: MV
authors.lastname: Scarpa
authors.affiliation: Departamento de Análises Clínicas, UNESP-Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, PPG em Nanotecnologia Farmacêutica, Rodovia Araraquara-Jaú Km 01, Araraquara, SP, Brazil.
authors.forename: Iracilda Zepone
authors.initials: IZ
authors.lastname: Carlos
authors.affiliation: Departamento de Análises Clínicas, UNESP-Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, PPG em Nanotecnologia Farmacêutica, Rodovia Araraquara-Jaú Km 01, Araraquara, SP, Brazil.
authors.forename: Marcela Bassi
authors.initials: MB
authors.lastname: Quilles
authors.affiliation: Instituto de Patologia Cirúrgica e Citopatologia (IPC), Araraquara, SP, Brazil.
authors.forename: Raphael Carlos Comeli
authors.initials: RC
authors.lastname: Lia
authors.affiliation: UFRN-Universidade Federal do Rio Grande do Norte, Programa de Pós-graduação em Ciências da Saúde, Natal, RN, Brazil.
authors.forename: Eryvaldo Socrates Tabosa
authors.initials: ES
authors.lastname: do Egito
authors.affiliation: Departamento de Fármacos e Medicamentos, UNESP-Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, PPG em Nanotecnologia Farmacêutica, Rodovia Araraquara-Jaú Km 01, Araraquara, SP, Brazil.
authors.forename: Anselmo Gomes
authors.initials: AG
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity; D003517:Cyclopentanes / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D004655:Emulsions / Q000737:chemistry / Q000633:toxicity; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003517:Cyclopentanes; D004337:Drug Carriers; D004655:Emulsions; C501952:methyldihydrojasmonate
keywords: Ehrlich ascitic tumor; angiogenesis inhibition; antitumor activity; antitumor drug; nanocarrier