Formulation and Evaluation of Eugenol/Glycyrrhizic Acid -Loaded Nano-Lipid Carrier Gel for Treating Multidrug-Resistant Oral Infections: Histological Changes in a Mouse Model

Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Candida albicans are pathogens that are drug-resistant and biofilm-forming. Therefore, they are responsible for severe infections, high morbidity, and mortality all over the world. Their ability to form biofilms and develop resistance against conventional antibiotics calls for a big need for new antimicrobial strategies. In this study, a nano-lipid carrier (NLC) gel containing eugenol and glycyrrhizic acid extract (EGAE) was developed as a topical treatment system and it was evaluated for its efficacy against multidrug-resistant (MDR) clinical isolates. The EGAE-NLC gel showed a very good physico-chemical stability by maintaining its visual appearance, uniform consistency, and drug content (98.9%) over a period of 12 weeks standard storage conditions. The gel formulation demonstrated a thermodynamically stable microemulsion with a globule size ranging between 29.1 and 60.5 nm. The zeta potential ranged from -35 to -43 mV and a pH range of 6.5–6.7. All these make the gel suitable for topical administration. The antimicrobial evaluation showed that the EGAE-NLC gel exerts a significant inhibitory activity against the studied pathogens, where a marked reduction in the minimum inhibitory concentrations (MICs) compared to individual components was attained. It is believed that the gel disrupted the biofilms and increased microbial cell membrane permeability. Eventually, leading to leakage of intracellular materials, cell lysis, and death. The anti-biofilm activity was seen as the highest against S. aureus, in which severe disruption of cell-to-cell connections was observed. In conclusion, this study suggests that EGAE-NLC gel represents a promising alternative antimicrobial therapy for fighting against infections caused by MDR pathogens. The mechanism of direct bactericidal action and biofilm disruption can provide a strong basis for further development into a clinically useful formulation.