Posaconazole loaded Lipid Polymer Hybrid Nanoparticles: Design and Development for Vaginal Drug Delivery

The treatment of recurrent vaginal fungal infections by topical application of antifungal agent is limited mainly due to poor solubility and low levels of the drug available at the site of action in the affected tissues. For this reason, research is being done on novel drug-delivery technologies and new therapeutic compounds. Posaconazole (POS) is a broad-spectrum antifungal reported to be effective in managing serious infections and drug-resistant fungal strains.

In the present study, lipid polymer hybrid nanoparticles (LPHNP) were prepared to achieve site-specific targeting and improve tissue uptake of POS. A sustained release profile and higher drug encapsulation are both rendered possible by the structural benefits of polymers and the biomimetic characteristics of lipids.

In the present study, LPHNP were prepared using POS, polycaprolactone (PCL), soya lecithin, and polyvinyl alcohol (PVA) as structural constituents by emulsification followed by solvent evaporation. The formulation batches were subsequently optimized using a 3-factor 3-level Box Behnken statistical design. Particle size, zeta potential, surface morphology by transmission electron microscopy (TEM), drug entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), and in vitro drug release were all employed to characterize the formulations. A cell viability assay was used to conduct cytotoxicity studies of the LPHNP on the SiHa cell line. The cellular uptake was assessed using a confocal laser scanning microscope and flow cytometry.

The particle size, polydispersity index (PDI), and zeta potential of the optimized LPHNP batch were found to be 465 ± 58.13 nm, 0.17 ± 0.07, and -12 mV respectively. The entrapment efficiency was found to be 90.92 ± 0.22%. The antifungal activity of POS-loaded LPHNP was significantly higher than the pure drug. The release of drug from the LPHNP system was observed to be sustained for up to 24 h. The in vitro cell cytotoxicity (MTT assay) and cellular uptake were evaluated using SiHa cell lines. The MTT assay of the developed LPHNP formulation demonstrated negligible cytotoxicity as compared to that of pure POS. The cell uptake studies by flow cytometry showed greater cell internalization of the formulation (58.4% after 4 h incubation) owing to the smaller particle size of the nanoparticles. Similar results (78% after 4 h incubation) were observed in confocal microscopy indicating probable higher therapeutic efficacy for deep-seated fungal infections.

Conclusively, LPHNP is a promising drug delivery system for vaginal targeting of therapeutic moieties.