# Endowed Polyphenols in Advanced Delivery Systems for Vaginal Infections
## 5 Oral Medication Versus Topical Application  
Contrary to urinary infections, in which the first line of medication is oral antibiotics (i.e., nitrofurantoin, fosfomycin or trimethoprim/sulfamethoxazole) [55], topical treatments of VI have shown to be at least as effective as an oral treatment in most cases, thus resulting in higher local drug concentrations and fewer drug interactions and adverse effects (Table 1) [56]. However, for recurrent symptoms, oral antibiotics, and maybe simultaneously medication, are inevitable. Each of the most common VIs has different clinical and pathological characteristics that have a significant impact on the efficacy of topical treatments and the development of effective topical approaches. A common occurrence is infection with several pathogenic microorganisms. This not only causes diagnostic difficulties, but also increases the risk of failure to treat a hidden overlapping problem, explaining the persistence of symptoms after a supposedly adequate treatment regimen for the identified clinical entity. Furthermore, the emergence of chemotherapeutic-resistant bacteria and the difficulties in managing infection recurrence underscore the need for more effective local treatments [56]. The therapeutic efficacy of conventional drugs can be improved by using formulation strategies that improve drug retention, solubility, and distribution in the vaginal tract, while also promoting drug interaction with pathogens and aiding in the recovery of the regular vaginal environment. To achieve these objectives, researchers must consider not only the physical and chemical properties of the drug and the overall formulation but also the specific features of the physiological environment that will be met after administration [56]. The amount, composition, microbiome, and pH of vaginal fluid are expected to influence the performance of vaginal drug delivery systems, as demonstrated in formulations subjected to physiologically simulated conditions [57; 58; 59]. There are several types of treatments for VIs (Table 1), including short-duration therapies. Yeast infections are often treated effectively with antifungal agents over a period of three to seven days. Common antifungal treatments include miconazole and clotrimazole, which are available in various forms such as creams, suppositories, and tablets. Some of these medications, like miconazole creams and clotrimazole passivaries, are available over the counter, while others, like fluonazole or butoconazole, may require a prescription. Brands like Vagisil(r) and Gino-canesten(r) also offer widely used products containing these active ingredients. The rise of resistance to existing antifungal and antibacterial treatments underscores the growing need for new therapeutic approaches in managing VIs. \begin{table}
**Active Ingredient** & **Indications** & **Dosage Form** & **Mechanism of Action** & **Reference** \\ \hline Clotrimazole & VVC & cream, Tablet, PSSary & Inhibits ergosterol synthesis in fungal cell & [60; 61] \\  & & & membranes, disrupting cell integrity. & \\ \hline \hline \end{tabular} \begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{Miconazole} & \multirow{2}{*}{VVC} & \multirow{2}{*}{Cream, Suppository} & \multirow{2}{*}{\begin{tabular}{c} Inhibits fungal cell membrane synthesis by \\ blocking ergosterol production. \\ \end{tabular} } & [62; 63] \\ \cline{1-1}  & & & \\ \hline \hline \end{tabular} \
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{Metronidazoleazole} & \multirow{2}{*}{BV, Trichomal vaginitis} & \multirow{2}{*}{Gel, Oral, Tablet} & Disrupts DNA synthesis in anaerobic bacteria & [64; 65] \\  & & & and protozoa. & \\ \hline \hline \end{tabular}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{Tinidazole} & \multirow{2}{*}{BV, Trichomal vaginitis} & \multirow{2}{*}{Oral Tablet} & DNA synthesis inhibition in anaerobic organisms. & [66; 67] \\ \cline{1-1}  & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Active ingredients for VI treatment.