Phase behavior of dioleyphosphatidylethanolamine molecules in the presence of components of pH-sensitive liposomes and paclitaxel.
Paclitaxel is a potent antimicrotubule chemotherapeutic agent widely used for clinical treatment of a variety of solid tumors. However, the low solubility of the drug in aqueous medium and the toxic effects of the commercially available formulation, Taxol(®), has hindered its clinical application. To overcome these paclitaxel-related disadvantages, several drug delivery approaches have been thoroughly investigated. In this context, our research group has developed long-circulating and pHsensitive liposomes containing paclitaxel composed of dioleylphosphatidylethanolamine, cholesterylhemisuccinate and distearoylphosphatidylethanolamine-polyethylene glycol2000, which have shown to be very promising carriers for this taxane. For the destabilization of pH-sensitive liposomal systems and the release of the encapsulated drug in the cytoplasm of tumor cells, the occurrence of a phase transition from a lamellar to a non-lamellar phase of dioleylphosphatidylethanolamine molecules is essential. Two techniques, differential scanning calorimetry and small angle X-ray scattering, were used to investigate the influence of the liposomal components and paclitaxel in the phase transition process of dioleylphosphatidylethanolamine molecules and to evaluate the pH-sensitivity of the formulation under low hydration conditions. The findings clearly evidence the phase transition of dioleylphosphatidylethanolamine molecules in the presence and absence of PTX indicating that the introduction of the drug in the system does not bring damage to the pH-sensitivity of the system, which resulting in liposome destabilization at low pH regions and encapsulated paclitaxel release preferentially in a desired target tissue.
Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
Liziane O F
LOF
Monteiro
Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
Sávia C A
SCA
Lopes
Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
André Luís B
ALB
Barros
Departamento de Física, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
Rogério
R
Magalhães-Paniago
Departamento de Física, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
Ângelo
Â
Malachias
Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
Mônica C
MC
Oliveira
Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. Electronic address: elaineleite@ufmg.br.
Elaine A
EA
Leite
D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry; D017239:Paclitaxel / Q000494:pharmacology*; D044367:Phase Transition / Q000187:drug effects; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D053838:Scattering, Small Angle; D012965:Sodium Chloride / Q000737:chemistry; D014961:X-Ray Diffraction
D008081:Liposomes; D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; D012965:Sodium Chloride; D017239:Paclitaxel
Cancer; Differential scanning calorimetry; Dioleylphosphatidylethanolamine; Paclitaxel; Phase transition; Small angle X-ray scattering; pH-sensitive liposomes