Characterization of miltefosine-loaded pluronic F127 polymeric micelles

VALENZUELA-OSES, JOHANNA; FEITOSA, VALKER A.; GARCÍA, MÓNICA C; RANGEL YAGUI, CARLOTA

Congreso; XV Brazil-Materials Research Society (B-MRS) Annual Meeting; 2016

Miltefosine is an alkylphosphocholine with antineoplastic activity. Miltefosine use is limited to topical application due to its high hemolytic potential. In this paper, we prepared miltefosine-loaded polymeric micelles aiming at lowering the drug hemolytic potential and improving solubility in aqueous media [1]. Miltefosine-loaded polymeric micelles were prepared by thin-film hydration method using the copolymer Pluronic 127 in a molar proportion of 9:7.2 (drug: polymer). A factorial design 23 was used to investigate the effect of three variables, namely film hydration temperature, stirring speed and stirring time on particle size (Dh) and polydispersity index (PDI). Initially, the critical micelle concentration (CMC) for the copolymer in phosphate buffer solution (PBS) was experimentally obtained employing a fluorescent probe (pyrene) and found to be 1.18 x 10-4 mol/L. Based on dynamic light scattering measurements (DLS), an average diameter of 25 nm was observed for all formulations with polydispersity index between 0.16 and 0.25. The mean hydrodynamic radius was found to be dependent of stirring speed and micellar polydispersity was found to be dependent of hydration temperature and stirring speed. An optimized formulation (Dh = 25.58 ± 0.34 nm and PDI = 0.167 ± 0.011) was obtained with film hydration at 50°C, stirring speed of 550 rpm and stirring time of 60 min. Micelle formation was confirmed by transmission electronic microscopy (TEM). Our results point to a stable miltefosine formulation that may allow the intravenous use of miltefosine. Acknowledgements: FAPESP, CAPES. References: [1] De Sá, M.; Rangel - Yagui, C.O. Molecular Determinants for the Binding Mode of Alkylphosphocholines in the C2 Domain of PKC alpha. Molecular Informatics, v. 34, p. 84 - 96, 2015.