Impact of components of biorelevant media on solubilization of methotrexate and sulfasalazine by Pluronic F127

IF 5.3 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Liquids Pub Date : 2024-11-24 DOI:10.1016/j.molliq.2024.126573

M.A. Agafonov, I.V. Terekhova

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引用次数: 0

Abstract

Pluronics are micelle-based solubilizers, improving the therapeutic potential of orally administrated drugs. In this connection, solubilizing action of Pluronics is being intensively studied in standard buffers simulating gastrointestinal fluids and consisting of inorganic components. However, human gastrointestinal fluids have more complicate composition due to the presence of organic compounds such as enzymes, mucus, and bile, which are able to form supramolecular aggregates and influence the solubilizing effect of Pluronics. Therefore, the use of specially designed biorelevant media is a promising approach to assessing the effectiveness of solubilizing activity of Pluronics in vitro.

Based on this, we studied the solubilization of poorly soluble methotrexate and sulfasalazine, which are used in the treatment of autoimmune and oncological diseases, by Pluronic F127 in Fasted State Simulated Gastric Fluid and Fasted State Simulated Intestinal Fluid. Taurocholic acid and lecithin being the main components of these biorelevant media form micelles and thereby enhance the solubility of drugs that are insoluble or sparingly soluble in water. The affinity of drugs under consideration to the micelles of different nature, which are present in the dissolution medium, is examined in this work. The possible competing interactions of drug-micelle and drug-unimer are discussed in terms of the ionization state of drug molecules and the nature of surfactants.

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生物相关介质成分对 Pluronic F127 对甲氨蝶呤和柳氮磺胺吡啶增溶作用的影响

Pluronics 是一种胶束增溶剂，可提高口服药物的治疗潜力。在这方面，目前正在模拟胃肠液的标准缓冲液中对 Pluronics 的增溶作用进行深入研究，缓冲液由无机成分组成。然而，由于酶、粘液和胆汁等有机化合物的存在，人体胃肠液的成分更为复杂，能够形成超分子聚集体，影响 Pluronics 的增溶作用。基于这一点，我们研究了 Pluronic F127 在禁食状态模拟胃液和禁食状态模拟肠液中对用于治疗自身免疫性疾病和肿瘤疾病的难溶性甲氨蝶呤和柳氮磺胺吡啶的增溶作用。这些生物相关介质的主要成分牛胆酸和卵磷脂会形成胶束，从而提高不溶于水或难溶于水的药物的溶解度。本研究探讨了药物与溶解介质中不同性质胶束的亲和性。根据药物分子的电离状态和表面活性剂的性质，讨论了药物-胶束和药物-单体之间可能存在的竞争性相互作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Liquids 化学-物理：原子、分子和化学物理

CiteScore

10.30

自引率

16.70%

发文量

2597

审稿时长

78 days

期刊介绍： The journal includes papers in the following areas: – Simple organic liquids and mixtures – Ionic liquids – Surfactant solutions (including micelles and vesicles) and liquid interfaces – Colloidal solutions and nanoparticles – Thermotropic and lyotropic liquid crystals – Ferrofluids – Water, aqueous solutions and other hydrogen-bonded liquids – Lubricants, polymer solutions and melts – Molten metals and salts – Phase transitions and critical phenomena in liquids and confined fluids – Self assembly in complex liquids.– Biomolecules in solution The emphasis is on the molecular (or microscopic) understanding of particular liquids or liquid systems, especially concerning structure, dynamics and intermolecular forces. The experimental techniques used may include: – Conventional spectroscopy (mid-IR and far-IR, Raman, NMR, etc.) – Non-linear optics and time resolved spectroscopy (psec, fsec, asec, ISRS, etc.) – Light scattering (Rayleigh, Brillouin, PCS, etc.) – Dielectric relaxation – X-ray and neutron scattering and diffraction. Experimental studies, computer simulations (MD or MC) and analytical theory will be considered for publication; papers just reporting experimental results that do not contribute to the understanding of the fundamentals of molecular and ionic liquids will not be accepted. Only papers of a non-routine nature and advancing the field will be considered for publication.