Chitosan-based sponges containing clotrimazole for the topical management of vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) persists as a worrying women's healthcare issue, often relying on suboptimal therapeutics. Novel intravaginal dosage forms focusing on improving patient acceptability and featuring improved biopharmaceutical properties could be interesting alternatives to available antifungal products. Different formulations of sponges based on chitosan (Ch), with or without crosslinking and co-formulated with poly(N-vinylcaprolactam) (PNVCL), were produced for the topical administration of clotrimazole (CTZ) and further tested for physicochemical properties, drug release, cytotoxicity and antifungal activity. Results showed that high amounts of CTZ (roughly 30-50 %) could be incorporated into sponges obtained by using a simple freeze-drying methodology. Cross-linking of Ch with ammonia affected the morphology and mechanical features of sponges and shifted the release profile from sustained (around 20 % and 60 % drug released after 4 h and 24 h, respectively) to fast-releasing (over 90 % at 4 h). The combination of PNVCL with non-crosslinked Ch also allowed tuning drug release, namely by increasing the initial amount of CTZ released in simulated vaginal fluid (roughly 40 % after 4 h), as compared to sponges featuring only non-crosslinked Ch. All formulations displayed low toxicity to cell lines derived from the female genital tract, with viability values kept above 70 % after 24 h incubation with sponge extracts. These also allowed maintaining the rapid onset of the antifungal effects of CTZ at minimum inhibitory concentrations ranging from 0.5 to 16 µg/mL for a panel of six different Candida spp. strains. Overall, proposed sponge formulations appear to be promising alternatives for the safe and effective management of VVC.

Assembly and antifungal effect of a new fluconazole-carrier nanosystem.

Aim: To assemble, characterize and assess the antifungal effects of a new fluconazole (FLZ)-carrier nanosystem. Materials & methods: The nanosystem was prepared by loading FLZ on chitosan (CS)-coated iron oxide nanoparticles (IONPs). Antifungal effects were evaluated on planktonic cells (by minimum inhibitory concentration determination) and on biofilms (by quantification of cultivable cells, total biomass, metabolism and extracellular matrix) of Candida albicans and Candida glabrata. Results: Characterization results ratified the formation of a nanosystem (<320 nm) with FLZ successfully embedded. IONPs-CS-FLZ nanosystem reduced minimum inhibitory concentration values and, in general, showed similar antibiofilm effects compared with FLZ alone. Conclusion: IONPs-CS-FLZ nanosystem was more effective than FLZ mainly in inhibiting Candida planktonic cells. This nanocarrier has potential to fight fungal infections.

Antifungal activity of silver nanoparticles in combination with nystatin and chlorhexidine digluconate against Candida albicans and Candida glabrata biofilms.

Although silver nanoparticles (SN) have been investigated as an alternative to conventional antifungal drugs in the control of Candida-associated denture stomatitis, the antifungal activity of SN in combination with antifungal drugs against Candida biofilms remains unknown. Therefore, the aim of this study was to evaluate the antifungal efficacy of SN in combination with nystatin (NYT) or chlorhexidine digluconate (CHG) against Candida albicans and Candida glabrata biofilms. The drugs alone or combined with SN were applied on mature Candida biofilms (48 h), and after 24 h of treatment their antibiofilm activities were assessed by total biomass quantification (by crystal violet staining) and colony forming units enumeration. The structure of Candida biofilms was analysed by scanning electron microscopy (SEM) images. The data indicated that SN combined with either NYT or CHG demonstrated synergistic antibiofilm activity, and this activity was dependent on the species and on the drug concentrations used. SEM images showed that some drug combinations were able to disrupt Candida biofilms. The results of this study suggest that the combination of SN with NYT or CHG may have clinical implications in the treatment of denture stomatitis. However, further studies are needed before recommending the use of these drugs safely in clinical situations.

Phase transformation in titania nanocrystals by the oriented attachment mechanism: the role of the pH value.

The oriented attachment (OA) mechanism has been investigated as an important process in the formation of anisotropic nanostructures such as depicted. The results showed that the control of a desired phase in this system may be attained by the control of OA mechanism through pH value, obtaining several morphologies.A new synthetic method for TiO(2) nanocrystals starting from metallic Ti and hydrogen peroxide was developed, in order to obtain minimal interferences to evaluate phase transformation in the system. The results revealed that the crystal morphology appeared to be dictated by the pH value, which shows a strong dependence on the surface energy. The involvement of the oriented attachment (OA) mechanism is important to modify the morphology and, hence, the distribution of the surface energy and confirmed that the mechanism can accelerate certain phase transitions, albeit pH dependence in terms of how the mechanism affects the final particle morphology and direction of crystalline growth. The importance of the mechanism was also apparent in extremely basic conditions, which indicates a possible correlation with the formation of hydrogen titanate nanostructures.