Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/120367
Author(s): Loureiro D.R.P.
Soares J.X.
Lopes D.
Macedo T.
Yordanova D.
Jakobtorweihen S.
Nunes C.
Reis S.
Pinto M.M.M.
Afonso C.M.M.
Title: Accessing lipophilicity of drugs with biomimetic models: A comparative study using liposomes and micelles
Publisher: Elsevier
Issue Date: 2018
Abstract: Lipophilicity is a physicochemical property of crucial importance in drug discovery and drug design. Biomimetic models, such as liposomes and micelles, constitute a valuable tool for the assessment of lipophilicity through the determination of partition coefficients (log Kp). However, the lack of standardization hampers the judgment about which model or method has the best and broadest passive drug permeation predictive capacity. This work provides a comparative analysis between the methodologies based on biomimetic models to determine the partition coefficient (log Kp). For that purpose, a set of reference substances preconized by the Organization for Economic Cooperation and Development (OECD) guidelines was used. The biomimetic models employed were liposomes and micelles composed by 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) and hexadecylphosphocholine (HePC), respectively. Both lipids were used as representative phospholipids of natural membranes. The partition coefficients between biomimetic models and aqueous phases were determined by derivative spectroscopy at physiological conditions (37 °C and pH 7.4). The partition coefficients obtained using biomimetic models are quite different and more reliable than the ones obtained using an octanol/water system. Comparing the performance of the two biomimetic models, micelles revealed to be suitable only for substances with high molar absorption coefficient and log Kp > 3, but in general liposomes are the best model for accessing lipophilicity of drugs. Furthermore, a comparison between experimental data and the partition coefficients determined by the computational method COSMOmic is also provided and discussed. As a final summarizing result, a decision tree is provided in order to guide the selection of a tool for assessing the lipophilicity of drugs. © 2018 Elsevier
Subject: dimyristoylphosphatidylcholine
liposome
miltefosine
phospholipid
drug
lipid
liposome
octanol
water
aqueous solution
Article
biomimetics
comparative study
lipophilicity
mathematical model
micelle
partition coefficient
physicochemical model
priority journal
spectrophotometry
biomimetics
chemistry
micelle
procedures
Biomimetics
Dimyristoylphosphatidylcholine
Lipids
Liposomes
Micelles
Octanols
Pharmaceutical Preparations
Phospholipids
Water
URI: https://hdl.handle.net/10216/120367
Source: European Journal of Pharmaceutical Sciences, vol. 115, p. 369-380
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:CIIMAR - Artigo em Revista Científica Internacional

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