Advanced Vaginal Nanodelivery of Losartan Potassium via PEGylated Zein Nanoparticles for Methicillin-Resistant Staphylococcus aureus.

Background/

Objectives

PEGylated zein nanoparticles (PZNs) loaded with losartan potassium (LOS) were developed as a repurposed treatment for vaginal methicillin-resistant Staphylococcus aureus (MRSA) infection. PZNs were prepared using the ethanol injection method with different types and amounts of Brij® surfactant.

Methods

The prepared formulations were optimized using a D-optimal mixture design via Design-Expert® software version 13. The assessed responses included entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP).

Results

The optimized PZNs, composed of 30 mg Brij® O20 and 10 mg zein, exhibited spherical particles with an EE% of 90.58 ± 1.20%, PS of 200.81 ± 1.39 nm, PDI of 0.395 ± 0.01, and ZP of -36.59 ± 0.05 mV. Confocal laser scanning microscopy confirmed complete deposition of fluorescein-labeled PZNs within vaginal tissues. Ex vivo studies showed that PZNs resulted in prolonged permeation of LOS compared to the LOS solution. In a murine model of MRSA infection, the optimized PZNs demonstrated superior therapeutic efficacy over the LOS solution. Histopathological examinations confirmed the safety of the tested formulations.

Conclusions

In conclusion, the optimized PZNs present a promising approach for the treatment of MRSA-related vaginal infections.