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

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.