Avaliação das propriedades físico-químicas e estruturais de lipossomas pH-sensíveis recobertos com polietilenoglicol carreadores de paclitaxel

Abstract

Paclitaxel (PTX) is a chemotherapeutic agent that has been shown significant antitumor activity for the treatment of a variety of cancers. However, the low solubility of PTX in aqueous medium represents a barrier to the development of formulations for intravenous administration. The commercially available formulation, Taxol®, has considerable side effects restricting its use. Thereby, the use of pH-sensitive liposomes covered by polyethyleneglycol is a potential alternative to carrier PTX (LpHS-PTX). Thus, the aims of this work were physicochemical characterization and evaluation of the structural organization of LpHS-PTX. Firstly, an analytical method for PTX quantification by high performance liquid chromatography was validated. The method was specific and accurate for the PTX quantification. LpHS-PTX presented adequate physicochemical properties including a mean diameter of 189 ± 3 nm, polydispersity index of 0.2, zeta potential of +1.40 mV and entrapment efficiency of 87 ± 0.6 %. Studies of Differential Scanning Calorimetry and Small Angle X-ray Scattering (SAXS) of formulation compounds, under low hydration conditions, revealed the phase transitions of the structural lipid, dioleoylphosphatidylethanolamine (DOPE), and showed that the inclusion of PTX in the bilayer did not compromise the pH-sensitivity system. SAXS studies under higher hydration conditions, revealed the pH-sensibility of LpHS-PTX over pH reduction. In the presence of fetal bovine serum, the interaction between LpHS-PTX and serum proteins, led to a formation of less ordered structures suggestive of supramolecular modifications. A comparative study of the effect of lipid composition on the pH-sensitivity showed that reducing the molar ratio of DOPE in the formulation resulted in a reduction of the pH-sensitive liposomes response. At different conditions of temperature, the absence of phase transition in the LpHS-PTX evidenced the stability of the system. Results confirm pH-sensitivity of the developed system, presenting LpHS-PTX as a promising alternative for intravenous administration of PTX in cancer treatment.