Electrosprayed chitosan microcapsules as delivery vehicles for vaginal phytoformulations.

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.

Antibacterial potential of non-volatile constituents of Rosmarinus officinalis against 37 clinical isolates of multidrug-resistant bacteria / Actividad antibacteriana de constituyentes no volátiles de Rosmarinus officinalis contra 37 aislamientos clínicos de bacterias multirresistentes

In this paper we investigated the antibacterial activity of a methanolic extract of Rosmarinus officinalis L. and their main constituents, carnosic acid and rosmarinic acid, against 37 nosocomial strains of multidrug-resistant bacteria. Results obtained showed that both the rosemary extract and carnosic acid inhibited all clinical isolates of Staphylococcus aureus methicillin-resistant and Enterococcus faecalis gentamicin and streptomycin-resistant bacteria examined (MICs 60 ug/mL vs. 200 ug/mL, respectively). Rosemary extract showed MIC values between 400 and 1600 ug/ml against the Gram-negative multidrug-resistant bacteria: Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa, Morganella morganii and Providencia stuartii, while carnosic acid showed MIC of 120 to 240 ug/mL. Bactericidal effect of carnosic acid against S. aureus and E. faecalis was observed at their MIC value, while 2 x MIC to 4 x MIC were needed to kill Gram-negative bacteria. Rosmarinic acid showed a narrow spectrum of action against a few Gram-negative clinical isolates. Our findings suggest that carnosic acid would be a good lead candidate useful in counteracting drug-resistant infections.

En este trabajo evaluamos la actividad antibacteriana de un extracto metanólico de Rosmarinus officinalis L. y sus principales componentes el ácido carnósico y ácido rosmarínico, contra 37 cepas de bacterias multirresistentes nosocomiales. Los resultados muestran que el extracto de romero y el ácido carnósico, inhibieron las bacterias Gram-positivas Staphylococcus aureus resistentes a meticilina y Enterococcus faecalis resistentes a gentamicina y estreptomicina (CIM 200 ug/mL y 60 ug/mL, respectivamente). El extracto de romero inhibió los Gram negativos multirresistentes: Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa, Morganella morganii y Providencia stuartii (CIM 400 a 1600 ug/mL), mientras que el ácido carnósico mostró valores de CIM entre 120 a 240 ug/mL. El ácido carnósico mostró actividad bactericida contra S. aureus y E. faecalis a su CIM, mientras que 2 a 4 X CIM se requirieron para matar las bacterias Gram-negativas. El ácido rosmarínico mostró inhibió unos pocos aislados clínicos Gram-negativos. Estos hallazgos sugieren que el ácido carnósico puede ser de utilidad contra infecciones bacterianas multirresistentes a antibióticos.

Effect of seasonality on chemical composition and antibacterial and anticandida activities of Argentine propolis. Design of a topical formulation.

The effect of seasonality on Argentine propolis collected during one year on its phenolic and flavonoid content and on the growth of Gram-positive and Gram-negative antibiotic resistant bacteria and Candida species was evaluated. Extracts of propolis samples collected in the summer and spring showed higher phenolic and flavonoid contents than the samples collected in other seasons (5.86 to 6.06 mg GAE/mL and 3.77 to 4.23 mg QE/mL, respectively). The propolis collected in summer and autumn showed higher antibacterial activity (30 microg/mL) than the other samples (MIC values between 30 and 120 microg/mL). No antibacterial activity was detected against Gram-negative bacteria. Also, these extracts were able to inhibit the development of five Candida species, with MFC values of 15-120 microg/mL. Pharmaceutical formulations containing the more active propolis extract were prepared. The hydrogel of acrylic acid polymer containing summer propolis extract as an antimicrobial agent showed microbiological, physical and functional stability during storage for 180 days. The pharmaceutical preparation, as well as the propolis extracts, was active against Candida sp. and antibiotic-multi-resistant Gram-positive bacteria. These results reveal that propolis samples collected by scraping in four seasons, especially in summer in Calingasta, San Juan, Argentina, can be used to obtain tinctures and hydrogels with antibacterial and antimycotic potential for topical use.

Antioxidant/antibacterial activities of a topical phytopharmaceutical formulation containing a standardized extract of Baccharis incarum, an extremophile plant species from Argentine Puna.

The antimicrobial and antioxidant activities of standardized extracts of Baccharis incarum in 60° and 80° ethanol and of a phytopharmaceutical formulation obtained from them were measured. Baccharis tinctures showed antimicrobial activity against clinically isolated antibiotic resistant Staphylococcus aureus and Enterococcus faecalis, with MIC values of 40-80 µg GAE/mL. Both tinctures exhibited ABTS(●+) scavenging activity with SC(50) values between 1.6 and 4.0 µg GAE/mL. The tinctures were not genotoxic in the Salmonella assay. For this reason, the tincture in 60° ethanol was incorporated into a topical pharmaceutical formulation (Hydrogel/ Carbopol® 934). The phytopharmaceutical formulation also showed antibacterial and antioxidant activities in the in vitro assays. The hydrogel showed microbiological, chemical, physical and functional stability during storage at room temperature. Studies that measure drug release as a determination of bioavailability were also carried out using the Franz diffusion cell (FC). The results demonstrated the release of two bioactive compounds (chlorogenic acid and 4',5-dihydroxy-3',3,6,7,8-pentamethoxyflavone) from the phytotherapic preparation in HPLC studies of FC receptor solution. In consequence, the phytopreparation applied topically could be used to treat skin and soft tissue infection produced by methicillin-resistant Staphylococcus aureus (MRSA) or Enterococcus faecalis and opens new opportunities for the use of active natural ingredients in the cosmeceutical field as antiacne and antioxidant.