大麻二酚-聚合物无定形固体分散体溶解趋势背后的分子相互作用

IF 5.2 1区化学 Q1 POLYMER SCIENCE

Macromolecules Pub Date : 2024-08-20 DOI:10.1021/acs.macromol.4c01579

Baris E. Ugur, Nicholas J. Caggiano, Stephanie Monson, Alexander G. Bechtold, Yejoon Seo, Robert K. Prud’homme, Rodney D. Priestley, Michael A. Webb

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引用次数: 0

摘要

大麻二酚（CBD）被认为是一种很有前景的治疗剂，可用于治疗多种健康疾病；然而，由于其水溶性较差，其疗效受到了限制。无定形固体分散体（ASD）可通过在聚合物基质中分散治疗药物来提高其溶解度。考虑到含有 CBD 的 ASD 配方，我们研究了 CBD 与各种聚合物的相互作用：聚乙烯吡咯烷酮（PVP）、聚乙烯吡咯烷酮/醋酸乙烯（PVP/VA）共聚物、羟丙基甲基纤维素邻苯二甲酸酯（HPMCP）、羟丙基甲基纤维素醋酸琥珀酸酯（HPMCAS）和聚甲基丙烯酸甲酯（PMMA）。实验和分子动力学模拟都揭示了这组聚合物之间多种多样的混合行为。详细的结构和纳米级相互作用分析表明，理想混合行为的正偏差源于稳定的聚合物-CBD 氢键的形成，而负偏差则与聚合物-聚合物氢键网络的破坏有关。聚合物与水的相互作用分析表明了聚合物疏水性的重要性，它可能导致 CBD 溶解不良。根据 CBD 和水与每种聚合物的相互作用方式，这些结果对药物溶出率有一定的影响。此外，这些见解还可用于指导 CBD 或其他小分子治疗药物的 ASD 配方。

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Molecular Interactions Underlying Dissolution Trends in Cannabidiol-Polymer Amorphous Solid Dispersions

Cannabidiol (CBD) is viewed as a promising therapeutic agent against a variety of health ailments; however, its efficacy is limited by poor aqueous solubility. Amorphous solid dispersions (ASDs) can enhance the solubility of therapeutics by distributing them throughout a polymer matrix. In consideration of ASD formulations with CBD, we investigate the interactions of CBD with various polymers: poly(vinylpyrrolidone) (PVP), poly(vinylpyrrolidone)/vinyl acetate (PVP/VA) copolymer, hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), and poly(methyl methacrylate) (PMMA). Both the experiment and molecular dynamics simulation reveal diverse mixing behavior among the set of polymers. Detailed structural and nanoscale interaction analyses suggest that positive deviations from ideal mixing behavior arise from the formation of stable polymer–CBD hydrogen bonds, whereas negative deviations are associated with disruptions to the polymer–polymer hydrogen bond network. Polymer–water interaction analyses indicate the significance of polymer hydrophobicity that can lead to poor dissolution of CBD. These results have implications for drug dissolution rates based on how CBD and water interact with each polymer. Furthermore, these insights may be used to guide ASD formulations for CBD or other small-molecule therapeutic agents.

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来源期刊

Macromolecules 工程技术-高分子科学

CiteScore

9.30

自引率

16.40%

发文量

942

审稿时长

2 months

期刊介绍： Macromolecules publishes original, fundamental, and impactful research on all aspects of polymer science. Topics of interest include synthesis (e.g., controlled polymerizations, polymerization catalysis, post polymerization modification, new monomer structures and polymer architectures, and polymerization mechanisms/kinetics analysis); phase behavior, thermodynamics, dynamic, and ordering/disordering phenomena (e.g., self-assembly, gelation, crystallization, solution/melt/solid-state characteristics); structure and properties (e.g., mechanical and rheological properties, surface/interfacial characteristics, electronic and transport properties); new state of the art characterization (e.g., spectroscopy, scattering, microscopy, rheology), simulation (e.g., Monte Carlo, molecular dynamics, multi-scale/coarse-grained modeling), and theoretical methods. Renewable/sustainable polymers, polymer networks, responsive polymers, electro-, magneto- and opto-active macromolecules, inorganic polymers, charge-transporting polymers (ion-containing, semiconducting, and conducting), nanostructured polymers, and polymer composites are also of interest. Typical papers published in Macromolecules showcase important and innovative concepts, experimental methods/observations, and theoretical/computational approaches that demonstrate a fundamental advance in the understanding of polymers.