Ana Palmeira-de-Oliveira

Anti-Candida activity of essential oils.

Anti-Candida activity of essential oils has been widely studied and as a consequence they are being investigated as possible alternatives or complementary therapeutic agents for candidosis. We reviewed the most studied essential oils concerning chemical composition and in vitro/in vivo studies under the perspective of their possible clinical use.

New strategies for local treatment of vaginal infections.

Vaginal infections are extremely prevalent, particularly among women of reproductive age. Although they do not result in high mortality rates, these infections are associated with high levels of anxiety and reduction of quality of life. In most cases, topical treatment of vaginal infections has been shown to be at least as effective as oral treatment, resulting in higher local drug concentrations, with fewer drug interactions and adverse effects. Furthermore, the emergence of microbial resistance to chemotherapeutics and the difficulties in managing infection recurrences sustain the need for more effective local treatments. However, conventional dosage forms have been associated with low retention in the vagina and discomfort. Formulation strategies such as the development of bioadhesive, thermogelling systems and microtechnological or nanotechnological approaches have been proposed to improve delivery of traditional drugs, and other treatment modalities such as new drugs, plant extracts, and probiotics are being studied. This article reviews the recent strategies studied to improve the treatment and prevention of the commonest vaginal infections-namely, vaginal bacteriosis, aerobic vaginitis, vulvovaginal candidosis, and trichomoniasis-through the intravaginal route.

Vaginal Films for Drug Delivery

Vaginal dosage forms have been studied in relation to many drugs as the vagina presents several advantages as a site for drug delivery, such as large surface area, rich blood supply, avoidance of the first-pass effect, relatively high permeability to several drugs, and self-insertion. Traditional vaginal dosage forms have been associated with disadvantages such as low residence time and discomfort and have been surpassed by newly designed drug delivery systems, particularly those based on bioadhesive polymers. Vaginal films are solid dosage forms that rapidly dissolve in contact with vaginal fluids and are unlikely to be associated with leakage and messiness. They have been studied for some female genital problems, aiming either contraceptive, antimicrobial, or microbicide effects. Precise and complex processes of manufacturing and characterization are required to achieve successful film formulation. Although scarce, the available users acceptability studies show promising results. Vaginal films gather a lack of opportunities for both therapeutic and prophylactic actions, and therefore should be considered when designing and developing new vaginal drug delivery systems.

Anti-biofilm activity of low-molecular weight chitosan hydrogel against Candida species.

AbstractCandida invasive infections have increased in frequency during the last decades. Such infections are often associated to medical indwelling devices like central venous catheter. The recurrent nature and difficulties in the treatment of these infections are often related to biofilm formation. The objective of this study was to investigate the anti-biofilm activity of low-molecular weight chitosan hydrogel (LMWCH), a natural biopolymer obtained from the N-deacylation of crustacean chitin, upon clinical relevant Candida species. The in vitro ability of LMWCH to impair biofilm formation and to disorganize a preformed biofilm was tested in polystyrene microplates and quantified by the semi quantitative XTT assay and by the crystal violet assay. LMWCH in vivo efficacy as a coating for medical indwelling devices was evaluated for the first time for Candida parapsilosis, using a mouse subcutaneous foreign body model using polyurethane catheter segments. Scanning electron microscopy was used to access biofilm architecture after LMWCH treatment. We found that LMWCH efficiently impaired biofilm formation of all Candida species, also promoting biofilm disaggregation. Most importantly, LMWCH was able to significantly inhibit biofilm formation by C. parapsilosis in an in vivo catheter mouse model. SEM images showed biofilm collapsed cells compatible with membrane damage, suggesting that this could be one of the possible mechanisms underlying biofilm impairment. LMWCH revealed to be a promising compound for treatment of candidiasis or its prevention through medical device coating.

Bacterial Vaginosis Biofilms: Challenges to Current Therapies and Emerging Solutions

Bacterial vaginosis (BV) is the most common genital tract infection in women during their reproductive years and it has been associated with serious health complications, such as preterm delivery and acquisition or transmission of several sexually transmitted agents. BV is characterized by a reduction of beneficial lactobacilli and a significant increase in number of anaerobic bacteria, including Gardnerella vaginalis, Atopobium vaginae, Mobiluncus spp., Bacteroides spp. and Prevotella spp.. Being polymicrobial in nature, BV etiology remains unclear. However, it is certain that BV involves the presence of a thick vaginal multi-species biofilm, where G. vaginalis is the predominant species. Similar to what happens in many other biofilm-related infections, standard antibiotics, like metronidazole, are unable to fully eradicate the vaginal biofilm, which can explain the high recurrence rates of BV. Furthermore, antibiotic therapy can also cause a negative impact on the healthy vaginal microflora. These issues sparked the interest in developing alternative therapeutic strategies. This review provides a quick synopsis of the currently approved and available antibiotics for BV treatment while presenting an overview of novel strategies that are being explored for the treatment of this disorder, with special focus on natural compounds that are able to overcome biofilm-associated antibiotic resistance.

The anti-Candida activity of Thymbra capitata essential oil: Effect upon pre-formed biofilm

ETHNOPHARMACOLOGICAL RELEVANCE [corrected] Thymbra capitata essential oil is traditionally considered to exhibit powerful antiseptic properties, thus being used to treat cutaneous infections. The aim of the present study was to evaluate the effect of Thymbra capitata essential oil upon pre-formed biofilm of different Candida strains while comparing it with the activity against planktonic cells. MATERIALS AND METHODS Fifteen Candida isolates were included, corresponding to clinical and collection type strains. Essential oil was obtained by hydrodistillation and its composition analysed by GC/MS. Activity upon planktonic cells was evaluated according to M27-A3 macromethod. Its effect upon 24h preformed biofilm biomass was determined using the crystal violet procedure and the metabolic activity was studied applying the XTT/menadione technique. RESULTS Biofilm biomass and metabolic activity of all tested species were reduced up to 50% at MIC values. The effect was more pronounced at double MIC values, achieving >80% reduction, except for Candida albicans that presented a more resistant profile (62%). CONCLUSION Thymbra capitata essential oil presented an important effect upon Candida biofilms. It is proposed as a valuable antifungal product to be used in an appropriate pharmaceutical formulation for the management of resistant mucocutaneous candidosis.

Coffee silverskin: A possible valuable cosmetic ingredient

Abstract Context: Currently, there is a great tendency in cosmetic area to use natural extracts. Coffee silverskin (CS) is the most abundant solid by-product generated during roasting of coffee processing. Objectives: To evaluate different CS extracts as promising cosmetic ingredients, regarding antioxidant, antimicrobial, and cytotoxic properties. Materials and methods: Aqueous, hydroalcoholic and ethanolic CS extracts were obtained by an environmentally friendly procedure considering costs and pollution. Extracts were characterized for total phenolic and flavonoid contents (TPC and TFC, respectively), antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), antimicrobial activity expressed as minimal inhibitory concentration (MIC) and cytotoxicity using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and lactate dehydrogenase (LDH) assays in two skin cell lines (fibroblasts and keratinocytes). Results: The TPC of extracts was 18.33–35.25 mg of gallic acid equivalents per g of material on a dry basis (mg GAE/g db). The TFC of extracts was 1.08–2.47 µg cathechin equivalents per g dry material (µg CE/g db). The antioxidant activity was high, with values ranging between 95.95 and 216.40 µmol Fe2+/g for aqueous and alcoholic samples, respectively. Preliminary assays for antimicrobial potential showed that extracts display antibacterial activity. The MIC varied from 31.3 to 250 µg/mL for Gram-positive, and from 31.3 to 1000 µg/mL for Gram-negative. Extracts did not affect in vitro cell viability, with values near 100% in all concentrations tested. Conclusion: Results seem show that CS is a safe source of natural antioxidants with antifungal and antibacterial activity and no cytotoxicity, with potential usefulness for cosmetic applications.

Characterization of Commercially Available Vaginal Lubricants: A Safety Perspective

Vaginal lubricants are widely used by women to help solve intercourse difficulties or as enhancers, but recent reports raise questions about their safety. Twelve commercially available gel products were tested for pH value, pH buffering capacity, osmolality and cytotoxicity relevant to vaginal delivery. Obtained data were analyzed in light of the recent Advisory Note by the World Health Organization (WHO) for personal lubricants to be concomitantly used with condoms. Results showed that most products do not comply with pH and osmolality recommended standards, thus posing a potential hazard. Four products presented values of osmolality around three-times higher than the maximum acceptable limit of 1200 mOsm/kg. In vitro cell testing further identified substantial cytotoxicity even at 1:100 dilutions for three products, contrasting with no significant effect of up to at least a 1:5 dilution of a Universal Placebo gel. However, no direct correlation between these last results and pH or osmolality was found, thus suggesting that the individual toxicity of specific formulation components plays an important role in the outcome of a particular product. Although further assessment is required, these results highlight potential safety issues related to the formulation of commercially available vaginal lubricants.

Sodium Tripolyphosphate: An excipient with intrinsic in vitro anti-Candida activity

Sodium Tripolyphosphate (STPP) is a food additive that is being used in the development of micro and nanoparticles as it induces ionic interactions with chitosan molecules. Although the ability of STPP to inhibit the growth of several food contaminants has been reported, studies on its activity against clinical isolates are scarce. Candida spp. are common causative agents of mucocutaneous infections including the vulvovaginal tegument and new therapeutic approaches are needed in order to treat resistant and recurrent cases. The aim of this study was to evaluate in vitro both antifungal (anti-Candida spp.) activity, and cytotoxicity, on human dermal fibroblasts, of STPP solutions. STPP showed an inhibitory species-dependent activity against several Candida spp. strains being particularly active on C. glabrata, followed by C. guilliermondii. In vitro, STPP showed a concentration dependent cytotoxicity. Therefore STPP use, in low concentrations, seems to be interesting in the development of drug delivery systems for the treatment of vulvovaginal candidosis.

In Vitro Anti-Candida Activity of Lidocaine and Nitroglycerin: Alone and Combined

The aim of this work was to study the anti-Candida activity of lidocaine and nitroglycerin alone and in combination. Ten Candida strains were included, corresponding to 1 collection type strain (ATCC 10231) and 9 clinical isolates: 4 C. albicans, 2 C. glabrata, 1 C. tropicalis, 1 C. krusei, and 1 C. parapsilosis. The CLSI reference M27-A3 micromethod was used to determine the anti-Candida activity of the drugs alone; minimal inhibitory and lethal concentrations were determined. The classic checkboard technique was used to determine the activity of combined drugs. Lidocaine fungicidal effect was dosedependent. Nitroglycerin exhibited a higher effect. The drugs combination resulted in a reduction of the inhibitory concentration, corresponding to an additive effect. In conclusion, both drugs exhibited an interesting anti-Candida activity. The combination of lidocaine with nitroglycerin was shown to have an additive effect against Candida spp., predicting the interest to include, in the future, these drugs in a new delivery system for the treatment of mucocutaneous candidosis.