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• W2969410881 abstract "Understanding how polyprotic compounds distribute within liposome (LP) suspensions is of major importance to design effective drug delivery strategies. Advances in this research field led to the definition of LP-based active drug encapsulation methods driven by transmembrane pH gradients with evidenced efficacy in the management of cancer and infectious diseases. An accurate modeling of membrane-solution drug partitioning is also fundamental when designing drug delivery systems for poorly endocytic cells, such as red blood cells (RBCs), in which the delivered payloads rely mostly on the passive diffusion of drug molecules across the cell membrane. Several experimental models have been proposed so far to predict the partitioning of polyprotic basic/acid drugs in artificial membranes. Nevertheless, the definition of a model in which the membrane-solution partitioning of each individual drug microspecies is studied relative to each other is still a topic of ongoing research. We present here a novel experimental approach based on mathematical modeling of drug encapsulation efficiency (EE) data in liposomal systems by which microspecies-specific partition coefficients are reported as a function of pH and phospholipid compositions replicating the RBC membrane in a simple and highly translatable manner. This approach has been applied to the study of several diprotic basic antimalarials of major clinical importance (quinine, primaquine, tafenoquine, quinacrine, and chloroquine) describing their respective microspecies distribution in phosphatidylcholine-LP suspensions. Estimated EE data according to the model described here closely fitted experimental values with no significant differences obtained in 75% of all pH/lipid composition-dependent conditions assayed. Additional applications studied include modeling drug EE in LPs in response to transmembrane pH gradients and lipid bilayer asymmetric charge, conditions of potential interest reflected in our previously reported RBC-targeted antimalarial nanotherapeutics." @default.
• W2969410881 created "2019-08-29" @default.
• W2969410881 creator A5026784302 @default.
• W2969410881 creator A5075346486 @default.
• W2969410881 creator A5075686017 @default.
• W2969410881 date "2019-09-25" @default.
• W2969410881 modified "2023-10-07" @default.
• W2969410881 title "Modeling the Distribution of Diprotic Basic Drugs in Liposomal Systems: Perspectives on Malaria Nanotherapy" @default.
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• W2969410881 doi "https://doi.org/10.3389/fphar.2019.01064" @default.
• W2969410881 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6773836" @default.
• W2969410881 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31611785" @default.
• W2969410881 hasPublicationYear "2019" @default.
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