两性霉素B包合物制剂在可溶解微阵列贴片用于阴道给药的研发。
Development of amphotericin B inclusion complex formulation in dissolvable microarray patches for intravaginal delivery.
作者信息
Burhanuddin Habiburrahim, Enggi Cindy Kristina, Tangdilintin Frederika, Saputra Rizki Rachmad, Putra Purnawan Pontana, Sartini Sartini, Aliyah Aliyah, Agustina Rina, Domínguez-Robles Juan, Aswad Muhammad, Permana Andi Dian
机构信息
Faculty of Pharmacy, Hasanuddin University, Makassar, 90245, Indonesia.
Department of Chemistry, Faculty of Mathematics and Natural Science, University of Palangka Raya, Central Kalimantan, 73111, Indonesia.
出版信息
Daru. 2024 Dec 12;33(1):5. doi: 10.1007/s40199-024-00546-7.
BACKGROUND
Amphotericin B (AMB) is a drug used to treat vulvovaginal candidiasis (VVC), which is a fungal infection affecting the vagina and vulva. Nevertheless, the substance's limited capacity to dissolve in water leads to poor absorption when taken orally, hence diminishing its therapeutic efficacy. In order to address this limitation, β-cyclodextrin (βCD) was used to create AMB in the form of an inclusion complex.
OBJECTIVE
This study aims to enhance the solubility and bioavailability of AMB by formulating it into an inclusion complex with βCD. Subsequently, we developed dissolvable microarray patches (DMP) as a novel drug delivery system, optimizing the formulation for improved retention, penetration, and controlled release of AMB.
METHODS
The stability of the AMB-βCD inclusion complx (IC) structure has been confirmed by employing molecular docking studies. The formulation of DMP involved the incorporation of IC with polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). The mechanical strength, ability to be inserted, and propensity to irritate Amphotericin B-Inclusion Complex-Dissolvable Microarray Patches (IC-DMP) were evaluated by laboratory experiments utilizing the porcine vaginal mucosal layer. Further investigations, such as Differential Scanning Calorimetry (DSC), were performed to assess the physicochemical characteristics of the IC.
RESULTS
The solubility of the pure medication was greatly enhanced up to fourfold by the inclusion complex. The assessment of IC-DMP exhibited exceptional mechanical robustness and insertion abilities, with no indications of discomfort. Among the formulas tested in ex vivo vaginal kinetic experiments, Formula F3 had the most effective retention in the porcine vaginal mucosal layer. It had an AUC value of 208.02 ± 0.33 h.µg/cm and the highest C value of 20.05 ± 0.06 µg/cm. Therefore, Formula F3 was the most efficient formula in terms of vaginal drug delivery.
CONCLUSION
The integration of IC into the DMP system significantly enhances the solubility and bioavailability of AMB, facilitating its absorption in the circulatory system when applied intravaginally for vulvovaginal candidiasis treatment. These promising initial findings support further clinical evaluation of this novel drug delivery system.
背景
两性霉素B（AMB）是一种用于治疗外阴阴道念珠菌病（VVC）的药物，VVC是一种影响阴道和外阴的真菌感染。然而，该物质在水中的溶解能力有限，口服时吸收不佳，从而降低了其治疗效果。为了解决这一局限性，使用β-环糊精（βCD）制备了包合物形式的AMB。
目的
本研究旨在通过将AMB与βCD制成包合物来提高其溶解度和生物利用度。随后，我们开发了可溶解微阵列贴片（DMP）作为一种新型药物递送系统，优化配方以改善AMB的保留、渗透和控释。
方法
采用分子对接研究证实了AMB-βCD包合物（IC）结构的稳定性。DMP的配方包括将IC与聚乙烯醇（PVA）和聚乙烯吡咯烷酮（PVP）混合。利用猪阴道黏膜层通过实验室实验评估两性霉素B包合物-可溶解微阵列贴片（IC-DMP）的机械强度、插入能力和刺激倾向。进行了差示扫描量热法（DSC）等进一步研究，以评估IC的物理化学特性。
结果
包合物使纯药物的溶解度大幅提高，最高可达四倍。IC-DMP的评估显示出优异的机械强度和插入能力，无不适迹象。在体外阴道动力学实验测试的配方中，配方F3在猪阴道黏膜层中的保留效果最有效。其AUC值为208.02±0.33 h.µg/cm，最高C值为20.05±0.06 µg/cm。因此，就阴道给药而言，配方F3是最有效的配方。
结论
将IC整合到DMP系统中可显著提高AMB的溶解度和生物利用度，在阴道内应用于外阴阴道念珠菌病治疗时促进其在循环系统中的吸收。这些有前景的初步发现支持对这种新型药物递送系统进行进一步的临床评估。
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