Everolimus-encapsulation in Pluronic P123 self-assembled micelles as drug delivery systems for drug-coated balloons

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2024-01-10 DOI:10.1016/j.ijpx.2024.100230
Mohammad Akrami-Hasan-Kohal , Adrien Chouchou , Sébastien Blanquer , Tahmer Sharkawi
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Abstract

Drug-coated balloons (DCBs) are effective tools for cardiovascular interventions, ensuring uniform drug delivery to occluded arteries. This research investigates the potential of Pluronic P123 (P123), a micelle-forming polymer, to solubilize and release Everolimus (EVE) from DCBs. Furthermore, it seeks to understand how the ratio of P123 to EVE affects release rates and micelle formation under physiological conditions. We tested three P123 to EVE ratios: 90:10, 75:25, and 50:50. Microscopy revealed that increasing EVE proportions resulted in more uniform coatings. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the successful incorporation of EVE into the P123 matrix without altering its chemical properties. Differential scanning calorimetry (DSC) studies showed that EVE incorporation affected the crystalline structure of P123, leading to more uniform coatings. In vitro release studies showed that all formulations had <1% drug loss in the first minute (the tracking phase); furthermore, the 90:10 ratio exhibited optimal drug release in the following 3 min, corresponding to the deployment phase in DCB angioplasty. Analysis of micelle loading capacity (LC), encapsulation efficiency (EE), size, and structure indicated an increase in both LC and EE with higher EVE content and a corresponding enlargement in micelle size. Given these findings, the optimized formula provided a consistent coating on commercial balloons, highlighting the potential of using P123 for DCB drug coating and release.

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将埃维莫司封装在 Pluronic P123 自组装胶束中,作为药物涂层球囊的给药系统
药物涂层球囊(DCB)是心血管介入治疗的有效工具,可确保向闭塞动脉均匀输送药物。本研究调查了形成胶束的聚合物 Pluronic P123(P123)从 DCB 中溶解和释放 Everolimus(EVE)的潜力。此外,该研究还试图了解在生理条件下,P123 与 EVE 的比例如何影响释放率和胶束的形成。我们测试了三种 P123 与 EVE 的比例:90:10、75:25 和 50:50。显微镜观察发现,增加 EVE 的比例可使涂层更均匀。傅立叶变换红外光谱(FTIR)分析证实,在不改变 P123 基质化学特性的情况下,EVE 成功地融入了 P123 基质中。差示扫描量热法(DSC)研究表明,EVE 的加入影响了 P123 的晶体结构,从而使涂层更加均匀。体外释放研究表明,所有配方在第一分钟(跟踪阶段)的药物损失率均为 1%;此外,90:10 比例的配方在随后的 3 分钟(相当于 DCB 血管成形术的展开阶段)表现出最佳的药物释放效果。对胶束负载能力(LC)、包封效率(EE)、大小和结构的分析表明,EVE 含量越高,LC 和 EE 都会增加,胶束的大小也会相应增大。鉴于这些发现,优化后的配方在商用球囊上提供了一致的涂层,突出了使用 P123 进行 DCB 药物涂层和释放的潜力。
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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
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