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Development of Doxorubicin hydrochloride loaded pH-sensitive liposomes: Investigation on the impact of chemical nature of lipids and liposome composition on pH-sensitivity.

07:00 EST 8th November 2018 | BioPortfolio

Summary of "Development of Doxorubicin hydrochloride loaded pH-sensitive liposomes: Investigation on the impact of chemical nature of lipids and liposome composition on pH-sensitivity."

This study investigates the impact of the chemical nature of lipids and additive on the formulation and properties of pH sensitive liposomes. The objective is to understand the respective role of the formulation parameters on the liposome properties in order to optimize the conditions for efficient encapsulation of doxorubicin (DOX). These liposomes should be stable at physiological pH, and disrupt in slightly acidic media such as the tumor microenvironment to release their DOX load. The major challenge for encapsulating DOX in pH sensitive liposomes lies in the fact that this drug is soluble at low pH (when the pH-sensitive liposomes are not stable), but the DOX aqueous solubility decreases in the pH conditions corresponding to the stability of the pH-sensitive liposomes. The study of pH-sensitivity of liposomes was conducted using carboxyfluorescein (CF) encapsulated in high concentration, i.e. quenched, and following the dye dequenching as sensor of the liposome integrity. We studied the impact of (i) the chemical nature of lipids (dioleoyl phosphatidyl ethanolamine (DOPE), palmitoyl-oleoyl phosphatidyl ethanolamine (POPE) and dimyristoyl phosphatidyl ethanolamine (DMPE)) and (ii)the lipid/stabilizing agent ratio (alpha-tocopheryl succinate), on the pH sensitivity of the liposomes. Optimized liposome formulations were then selected for the encapsulation of DOX by an active loading procedure, i.e. driven by a difference in pH inside and outside the liposomes. Numerous experimental conditions were explored, in function of the pH gradient and liposome composition, which allowed identifying critical parameters for the efficient DOX encapsulation in pH-sensitive liposomes.

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This article was published in the following journal.

Name: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ISSN: 1873-3441
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