# Natural Molecules, Nutraceuticals, and Engineered Nanosystems: A Comprehensive Strategy for Combating Gardnerella vaginalis-Induced Bacterial Vaginosis

## TL;DR

This paper explores natural compounds and nanotechnology as new ways to treat bacterial vaginosis caused by Gardnerella vaginalis, aiming to improve on current antibiotic treatments.

## Contribution

The paper introduces a novel strategy combining natural molecules and nanosystems to combat drug-resistant Gardnerella vaginalis infections.

## Key findings

- Natural compounds and nutraceuticals show antibacterial and antibiofilm properties against G. vaginalis.
- Engineered nanosystems enhance the delivery and efficacy of these natural agents.
- Nature-inspired therapies demonstrate superior in vitro and in vivo performance compared to traditional antibiotics.

## Abstract

Bacterial vaginosis (BV) is a highly prevalent vaginal infection characterized by a dysbiotic shift in the vaginal microbiota, with Gardnerella vaginalis acting as a principal pathogen. Despite its association with adverse reproductive outcomes, BV remains underexplored from both mechanistic and therapeutic standpoints. Standard antibiotic regimens frequently fail due to high recurrence rates driven by multidrug-resistant (MDR) G. vaginalis strains and biofilm formation. In response, natural compounds and nutraceuticals, owing to their intrinsic antibacterial, antibiofilm, and immunomodulatory properties, have emerged as promising candidates for alternative BV therapies. In this paper, we first compile and critically evaluate preclinical and clinical evidence on the efficacy of plant extracts, essential oils (EOs), probiotics, vitamins, proteins, fatty acids, and enzymes against G. vaginalis, emphasizing their mechanistic insights in restoring vaginal microbial balance. Next, we focus on the integration of these bioactive agents into engineered nanosystems, such as lipid-based nanoparticles (LNPs), polymeric carriers, and inorganic nanostructures, to overcome limitations related to solubility, stability, and targeted delivery. Nonetheless, comparative studies, combination therapies, and recent patent developments are discussed to highlight how naturally derived molecules can enhance antimicrobial potency and reduce cytotoxicity. In conclusion, these platforms demonstrate superior in vitro and in vivo efficacy, offering a paradigm shift in the management of BV. Key challenges include scalable manufacturing, regulatory approval, and comprehensive safety assessment. Future research should prioritize standardized nanoparticle (NP) synthesis, detailed pharmacokinetic and toxicity profiling, and well-designed clinical trials to validate nature-inspired, nanoengineered therapies against G. vaginalis-induced BV.