The design of novel delivery systems to treat vaginal fungal infections is a topic of high interest. Chitosan, being itself antimicrobial and having good mucoadhesive properties, is an excellent candidate as a delivery matrix for active compounds. In this work, chitosan microcapsules containing dry extracts of Argentinean medicinal plants with proved biological properties (Larrea divaricata, L. cuneifolia, L. nitida, Zuccagnia punctata and Tetraglochin andina) were developed through electrospraying and compared with conventionally used tablets containing the same extracts. Total phenolics, loading efficacy, physical properties, morphology and particle size, molecular organization, water sorption capacity, release of bioactive compounds and biological properties were assessed. The encapsulation process or the inclusion in tablets did not degrade the bioactive compounds of the extracts. The release of phenolic compounds from chitosan microcapsules was faster than from tablets. The fingerprint of released phenolic compounds from microcapsules and tablets was similar to that from the dry extracts and the antioxidant and antifungal capacity remained unchanged. The FT-IR analysis suggested interactions between the chitosan and the extracts, which explained why the microcapsules kept the integrity in slightly acidic media. Increased solubility of the extracts when incorporated in the microcapsules was seen in simulated vaginal fluid, potentially increasing the bioavailability of bioactive compounds in the vaginal environment. This work highlights the potential of the chitosan-based delivery systems for phytomedicines with antifungal and antioxidant activity to be used in vulvovaginal candidiasis.

Larrea divaricata (Ld), Larrea cuneifolia (Lc) and Larrea nitida (Ln) are shrubs occurring in Northwestern Argentina used in traditional medicine to treat fungal and bacterial infections and as anti-inflammatory. Antibacterial and antifungal activity of several Larrea species has been reported. However, their potential use in vaginal infections has been so far not assessed. The aim of this work was to determine the botanical difference between Larrea species, the chemical composition and the activity of Larrea dry extracts (DE) on Candida species isolated from vaginal infections and to assess their potential as antioxidant agents because infections are usually associated with oxidative processes. The main botanical difference between Larrea species resides in the morphology and shape of leaf, leaflets and stipules, presence or absence of mucron and rachis, percentage of coalescence of the leaflets. The position and abundance of the sclerenchymatic tissue at the mind vein and petiole transection allows the differentiation of the three species. The profile of phenolic compounds in the Larrea DE was determined. HPLC-ESI-MS/MS analysis of DE allowed the identification of 2 flavonoids and 10 lignans. Trihydroxy-6,7′cyclolignan was found only in L. divaricata and dihydroxy-methoxy-epoxylignan in L. cuneifolia and L. nitida, nordihydroguaiaretic acid (NDGA) was found in the three species. All extracts showed antioxidant capacity. The DE showed to be effective against Candida albicans and non-albicans strains. According to our results, the local vaginal use of Larrea DE in the concentration range of MIC values for Candida species does not affect the Lactobacillus normal vaginal microbiota. This work adds evidence to the potential use of Larrea DE as phytomedicine in vulvovaginal candidiasis with multiple effects, including antifungal and antioxidant activity.

Medium and high polarity extracts from Maytenus species are known to contain polyphenolic compounds such as proanthocyanidins. The high polarity and structural complexity of these compounds make very difficult their isolation even by modern chromatographic techniques. Maytenus cajalbanica (Borhidi & O. Muñiz) Borhidi & O. Muñiz is endemic from Cuba. So far, there are reports neither of phytochemical work nor of biological evaluation of extracts from this subspecies. The goal of this work is to determine the polyphenolic profile and the antioxidant capacity of the ethanolic extract from the barks of Maytenus cajalbanica. FIA/ESI/IT/MSⁿ analysis allowed the identification of 5 flavan-3-ol monomers, 33 proanthocyanidins, 2 free flavonoids and their respective glycosides as major compounds of the ethanolic extract, which showed a strong radical scavenging capacity and a significant ferric reduction power. FIA/ESI/IT/MSⁿ technique led the rapid, effective and sensitive determination of the polyphenolic profile of Maytenus cajalbanica without previous separation. GRAPHICAL ABSTRACT

The Chilean papaya (Vasconcellea pubescens A.DC.) is a climacteric fruit that grows in the north and center of Chile. During its processing, residues formed mainly by mucilage and seeds are produced and mostly discarded, despite being a potential source of bioactive metabolites. This work aimed to apply untargeted metabolic analysis by HPLC-DAD-QToF to study the chemical composition of ethyl acetate and methanol extracts from Chilean papaya residues and evaluate their antioxidant and antiglycation capacities. Twenty-three metabolites were tentatively identified in papaya residues, including one carboxylic acid, one glycosylated hydroquinone, four flavan-3-ols, three proanthocyanidins, twelve glycosylated flavonols, one carbohydrate, and one alkaloid reported for the first time. The antioxidant capacity measured as the scavenging of DPPH • and ABTS •+ radicals was comparable with that of ascorbic acid. Chilean papaya extracts decreased fluorescent Advanced Glycation End (AGE) products and oxidative modifications in proteins induced by glucose.