# Endowed Polyphenols in Advanced Delivery Systems for Vaginal Infections
## 7 Polyphenols in Advanced Systems
(2017) [156] constructed an in situ thermosensitive hydrogel delivery system based on amino-functionalized polyoxamer 407 (F127-NH2) for vaginal administration of acetate gossypol, a polyphenic aldehyde. This hydrogel exhibited controlled release while having mucoadhesive properties, which derived from the amino (NH2) functionalization of polyoxamer 407 (F127). As seen above, the research on the administration of polyphenols using advanced delivery systems for vaginal applications (Figure 3) is still limited. In this context, an analysis of other delivery systems with polyphenols, with distinct applications, can give suggestions for the development of novel forms for vaginal administration. Most of those other systems comprise protein-, metal-, polymer-, small molecule-, and nucleic acid-polyphenol-based nano delivery systems [157, 158]. These include nanoparticles (solid lipid nanoparticles, nanostructured lipid carriers), nanoemulsions, nanocapsules, liposomes, and nano hydrogels, among others [159, 160, 161]. Also, a recently published paper by our group [155] reported some more examples of potential nano delivery systems (e.g., dendrimers, niosomes) for polyphenols, summarizing their advantages. For example, [PERSON] et al. [162] concluded that chitosan-based liposomes successfully loaded resveratrol with an encapsulation efficiency of approx. 75% for topical treatment of vaginal inflammation and infection. Furthermore, [PERSON] et al. [163], for nutraceutical purposes, prepared resveratrol-loaded niosomes composed of Tween 20/Span 60 and cholesterol. These compounds showed minimal cytotoxicity for intestinal  
Figure 3: Polyphenols in advanced delivery systems for vaginal administration. nal cells, displaying potential for oral intake. [PERSON] et al. [164] developed a dual drug-loaded nanostructured lipid carrier (NLC) gel, with resveratrol and quercetin for improved disposition in skin layers, obtaining a resveratrol encapsulation efficiency of almost 90%. [PERSON] et al. [165] created resveratrol-loaded nanoemulsions using Caporyl 90 or isopropyl myristate as the oil phase, and propylene glycol and ethanol as cosurfactants. After 24 applications, the particles increased transdermal penetration and resveratrol deposition in the skin by 896.2- and 10.2-fold, respectively, when compared to the drug solution group. An in vivo study found that resveratrol plasma concentrations remained high for a long period following topical emulsion application. [PERSON] et al. [166] found that using polyamidoamide dendrimers improved resveratrol solubility and stability in aqueous and semisolid dose forms. Furthermore, the dendrimer enhanced resveratrol loading and skin penetration. [PERSON] et al. [167] encapsulated resveratrol in bovine serum albumin-coated layered double hydroxide (LDH-BSA), allowing a better encapsulation efficiency when compared to only LDH. Moreover, [PERSON] et al. [168] showed that resveratrol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles functionalized with red blood cell membranes have a better half-life and mean residence time when compared to simple resveratrol-loaded PLGA nanoparticles. Table 2 summarizes the examples mentioned above. Such knowledge can be transferred towards new forms for the treatment of VI.