Dual-Responsive Micellar Microgels Matrixed with Surface-Engineered Lipids: a New Approach for Controlled Vaginal Drug Delivery

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmaceutical Innovation Pub Date : 2021-06-10 DOI:10.1007/s12247-021-09546-5

Franklin C. Kenechukwu, Mumuni A. Momoh, Petra O. Nnamani, Chukwuebuka E. Umeyor, Emmanuel M. Uronnachi, Marcos L. Dias, Emmanuel C. Ibezim, Anthony A. Attama

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引用次数: 4

Abstract

Purpose

This study investigated surface-modified dual-responsive (bio-responsive and thermo-sensitive) micellar microgels as a novel vaginal drug delivery system (VDDS) for enhanced administration and prolonged localized efficacy.

Methods

Lipid matrices (LMs) consisting of Softisan® 154 and super-refined sunseed oil with or without PEG-4000 were prepared by fusion, loaded with a model topical vaginal drug (miconazole nitrate, MN), characterized and used to formulate MN-loaded surface-modified solid lipid microparticles (SLMs) by melt-homogenization. Surface-modified SLMs were characterized, lyophilized, and used to prepare surface-modified mucoadhesive and thermosensitive microgels (MTMs) employing three bioadhesive agents—hydroxypropylcellulose (HPC), Carbopol® 71G-NF or Polycarbophil®, each alongside two thermosensitive polymers (Kolliphor® P407 and Kolliphor® P188). The MTMs were characterized using phase transition temperature (PTT) and gelation time and evaluated for physicochemical performance, drug dissolution in simulated vaginal fluid (SVF, pH = 4.2) and stability. Antifungal efficacy of optimized (Kolliphor + HPC-based) microgels was evaluated against Candida albicans and compared with control.

Results

Solid-state characterizations confirmed amorphicity of LMs and MN-loaded LMs and stability of MN in the formulations. Viscoelastic MTMs with high drug content, PTT above room temperature, acceptable gelation times (110.00 ± 2.50 to 130.00 ± 7.80 s), and pH values suitable for VDD were obtained. Furthermore, optimized MTMs gave significantly (p < 0.05) greater prolonged drug release in SVF and higher anticandidal activity than commercial formulation (Daktarin®) and MN polymeric-hydrogel.

Conclusion

Dual-responsive micellar microgels represent a promising nonconventional formulation for prolonged localized VDD of MN.

Abstract Image

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双响应胶束微凝胶基质与表面工程脂:一种新的方法来控制阴道给药

目的研究表面修饰的双响应(生物响应和热敏)胶束微凝胶作为一种新的阴道给药系统(VDDS)，以增强给药能力和延长局部疗效。方法采用融合法制备Softisan®154和超精炼葵籽油(含或不含PEG-4000)组成的脂质基质(LMs)，负载一种阴道外用药物(硝酸咪康唑，MN)，对其进行表征，并通过熔融均质法制备负载MN的表面修饰固体脂质微粒(SLMs)。对表面改性的slm进行表征、冻干，并使用三种生物粘合剂(羟丙基纤维素(HPC)、Carbopol®71G-NF或Polycarbophil®)制备表面改性的粘胶剂和热敏微凝胶(MTMs)，每种粘合剂与两种热敏聚合物(Kolliphor®P407和Kolliphor®P188)一起使用。采用相变温度(PTT)和凝胶时间对MTMs进行了表征，并对其理化性能、在模拟阴道液(SVF, pH = 4.2)中的药物溶出度和稳定性进行了评价。评价优化后的(Kolliphor + hpc基)微凝胶对白色念珠菌的抑菌效果，并与对照进行比较。结果固态表征证实了LMs和MN负载LMs的非晶性以及配方中MN的稳定性。获得了药物含量高、PTT高于室温、可接受胶凝时间(110.00±2.50 ~ 130.00±7.80 s)和适合VDD的pH值的粘弹性MTMs。此外，与商业配方(Daktarin®)和MN聚合物水凝胶相比，优化后的MTMs具有显著(p < 0.05)更长的SVF药物释放时间和更高的抗兴奋剂活性。结论双响应胶束微凝胶是一种很有前途的用于治疗MN的长效局部VDD的非常规制剂。

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 Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-

CiteScore

3.70

自引率

3.80%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.