Exploring the antifungal potential of Annona muricata leaf extract-loaded hydrogel in treating vulvovaginal candidiasis.

Vulvovaginal candidiasis, mostly caused by Candida albicans, remains a prevalent concern in women's health. Annona muricata L. (Annonaceae), a plant native from Brazil, is well-known for its therapeutic potential, including antitumor, anti-inflammatory, and antimicrobial properties. This study presents an innovative hydrogel formulation containing the ethanolic extract from A. muricata leaves designed to control C. albicans in an in vivo model of vulvovaginal candidiasis. Here, we report the development, thermal, physicochemical and rheological characterization of a Carbopol®-based hydrogel containing A. muricata extract. Furthermore, we evaluated its activity in a vulvovaginal candidiasis in vivo model. Thermal analyses indicated that the addition of the extract increased the polymer-polymer and polymer-solvent interactions.Rheological analysis showed a decrease in the viscosity and elasticity of the formulation as the A. muricata extract concentration increased, suggesting a liquid-like behavior. After treatment with the Carbopol®-based hydrogel with A. muricata, our in vivo results showed a significant reduction in vulvovaginal fungal burden and infection, as well as a reduction in mucosal inflammation. The current research opens up possibilities for the application of the Carbopol®-based hydrogel with A. muricata as a natural therapeutic option for the treatment of vulvovaginal candidiasis.

Chitosan-based films filled with nanoencapsulated essential oil: Physical-chemical characterization and enhanced wound healing activity.

The economic burden of chronic wounds, the complexity of the process of tissue repair and the possibility of resistant bacterial infections, have triggered a significant research interest in the application of natural alternative therapies for wound healing. Biomolecules are intrinsically multi-active, as they affect multiple mechanisms involved in tissue repair phenomenon, including immunomodulatory, anti-inflammatory, cell proliferation, extra cellular matrix remodeling and angiogenesis. Chitosan features a unique combination of attributes, including intrinsic hemostatic, antimicrobial, and immunomodulatory properties, that make it an exceptional candidate for wound management, in the development of wound dressings and scaffolds. In this study, we produced nanoemulsions (NE) loaded with SFO, characterized them, and evaluated their tissue repairing properties. Dynamic light scattering (DLS) analysis confirmed the formation of a nanoemulsion with a droplet size of 21.12 ± 2.31 nm and a polydispersity index (PdI) of 0.159, indicating good stability for up to 90 days. To investigate the potential wound healing effects, SFO-loaded NE were applied on male C57BL/6 mice for seven consecutive days, producing a significantly higher wound closure efficiency (p < 0.05) for the group treated with SFO-loaded NE compared to the control group treated with the saline solution. This finding indicates that the SFO-loaded NE exhibits therapeutic properties that effectively promote wound healing in this experimental model. Then, SFO-loaded NE were incorporated into chitosan:polyvinyl alcohol (PVA)-based films. The inclusion of NE into the polymer matrix resulted in increased lipophilicity reflected by the contact angle results, while decreasing moisture absorption, water solubility, and crystallinity. Moreover, FTIR analysis confirmed the formation of new bonds between SFO-NE and the film matrix, which also impacted on porosity properties. Thermal analysis indicated a decrease in the glass transition temperature of the films due to the presence of SFO-NE, suggesting a plasticizing role of NE, confirmed by XRD results, that showed a decrease in the crystallinity of the blend films upon the addition of SFO-NE. AFM images showed no evidence of NE droplet aggregation in the Chitosan:PVA film matrix. Moisture absorption and water content decreased upon incorporation of SFO-loaded NE. Although the inclusion of NE increased hydrophobicity and water contact angle, the values remained within an acceptable range for wound healing applications. Overall, our results emphasize the significant tissue repairing properties of SFO-loaded NE and the potential of Chitosan:PVA films containing nanoencapsulated SFO as effective formulations for wound healing with notable tissue repairing properties.

Nanosystems for gene therapy targeting brain damage caused by viral infections.

Several human pathogens can cause long-lasting neurological damage. Despite the increasing clinical knowledge about these conditions, most still lack efficient therapeutic interventions. Gene therapy (GT) approaches comprise strategies to modify or adjust the expression or function of a gene, thus providing therapy for human diseases. Since recombinant nucleic acids used in GT have physicochemical limitations and can fail to reach the desired tissue, viral and non-viral vectors are applied to mediate gene delivery. Although viral vectors are associated to high levels of transfection, non-viral vectors are safer and have been further explored. Different types of nanosystems consisting of lipids, polymeric and inorganic materials are applied as non-viral vectors. In this review, we discuss potential targets for GT intervention in order to prevent neurological damage associated to infectious diseases as well as the role of nanosized non-viral vectors as agents to help the selective delivery of these gene-modifying molecules. Application of non-viral vectors for delivery of GT effectors comprise a promising alternative to treat brain inflammation induced by viral infections.

Advances in nanotechnology-based hair care products applied to hair shaft and hair scalp disorders.

OBJECTIVE: Nanotechnology has been intensively applied to the development of novel cosmetic products for hair and scalp care during the last decades. Such a trend is corroborated by the fact that about 19% of the total nanocosmetics registered in the StatNano database are intended for hair and scalp care. Nanotechnology-enabled formulations based on nanoparticles, cyclodextrins, liposomes and nanoemulsions have emerged as novel approaches due to chemical stability and their controlled release. Regarding hair care formulations, nanocarriers can target the hair shaft, hair follicle and scalp. Therefore, they have been used to treat several hair disorders, including dandruff and other hair-damaging conditions. METHODS: This review addressed the most important nanocarriers applied to hair-related disorders improvement. Furthermore, the application for hair photoprotection and improvement of hair colour duration by nanotechnological formulations is also approached. Besides, we provided an overview of the current scenario of available nano-based commercial hair products and novel patented inventions. RESULTS: From the patent search, the Patent Cooperation Treaty was pointed as the most important depositing agency while the United States of America has been the most depositing country. On the contrary, according to the StatNano database, Brazil stands out in the hair care worldwide market, and it is also the main producer of hair cosmetics based on nanotechnology. CONCLUSION: As nano-based products offer several advantages over conventional cosmetics, it is expected that in future, there will be more research on nanocarriers applied to hair disorders, as well as commercial products and patent applications.

Au cours des dernières décennies, les nanotechnologies ont été intensivement appliquées au développement de nouveaux produits cosmétiques pour le soin des cheveux et du cuir chevelu. Cette tendance est corroborée par le fait qu'environ 19% du nombre total de nano-cosmétiques enregistrés dans la base de données StatNano sont destinés à la fois aux soins des cheveux et du cuir chevelu. Les formulations basées sur les nanoparticules, les cyclodextrines, les liposomes et les nano-émulsions sont devenues de nouvelles approches grâce à l'amélioration de la stabilité chimique des médicaments et des ingrédients actifs cosmétiques et à leur libération contrôlée. En ce qui concerne les formulations de soins capillaires, les nanocarriers peuvent cibler le follicule pileux, la tige des cheveux et du cuir chevelu. Par conséquent, ils ont été utilisés pour traiter plusieurs troubles capillaires, notamment les pellicules et d'autres affections capillaires. Dans cette revue, les nano-carriers les plus importants appliqués à l'amélioration des troubles liés aux cheveux ont été abordés. L'application pour la photoprotection des cheveux et l'amélioration de la durée de la couleur des cheveux par des formulations nanotechnologiques est également abordée. En outre, nous fournissons un aperçu du scénario actuel des produits capillaires commerciaux à base des nanotechnologies disponibles et des nouvelles inventions brevetées. D'après la recherche de brevets, le Traité de coopération en matière de brevets a été désigné comme l'agence de dépôt la plus importante, tandis que les États-Unis d'Amérique ont été le pays le plus déposant. Diversement, le Brésil se distingue sur le marché mondial des soins capillaires et il est aussi le principal producteur de cosmétiques capillaires basés sur les nanotechnologies. Par conséquent, comme les produits à base de nanotechnologies offrent plusieurs avantages par rapport aux cosmétiques conventionnels, on s'attend à ce que les recherches sur les nano-carriers appliqués aux troubles capillaires se multiplient à l'avenir, de même que les produits commerciaux et les demandes de brevets.

Chitosan-based films containing nanoemulsions of methyl salicylate: Formulation development, physical-chemical and in vitro drug release characterization.

Transdermal patches for analgesic purposes are widely used, however, their occlusive characteristics can often cause allergic reactions, irritating contact dermatitis, and allergic contact dermatitis upon extended use. Chitosan is a natural positively charged bioadhesive polysaccharide with several biological properties, being promising templates for sustained and controlled topical or transdermal drug delivery. Methyl salicylate (MS) is a non-steroidal topical anti-inflammatory drug (NSAID). MS is a lipophilic oily drug commonly found in transdermal patches, being difficult to incorporate into hydrophilic formulations such as Chitosan-based films. Thus, MS is a good candidate to be encapsulated into nanoemulsions (NE). This work reports the formulation development, physical-chemical characterization, and in vitro drug release of NE-loaded Chitosan films formulated with MS, as a novel substitute for transdermal analgesic patches. MS was encapsulated into NE, which were prepared by ultrasonication and presented 29.3 nm ± 0.1 and PdI 0.167 ± 0.005. The incorporation of MS into NE prevented phase separation and provided a homogeneous physical blending formulation, as confirmed by FTIR, TGA. NE-loaded films provided high drug incorporation in the films 94.08% ± 6.63%), and a smaller crystallinity degree in comparison with physical mixture films, suggesting a plasticizing effect of nano-sized droplets. Besides, mean weight, thickness, and moisture content were increased in NE-loaded films in comparison with chitosan-based control films. In vitro drug release from NE-loaded films was significantly higher than for physical mixture films, following Weibull and Korsmeyer-Peppas release kinetics models. The results suggest that NE-loaded chitosan film can increase the drug loading capacity of oil drugs and successfully control in vitro release, constituting a novel approach for transdermal drug delivery of NSAIDs.

Formulation characterization and in vitro drug release of hydrogel-thickened nanoemulsions for topical delivery of 8-methoxypsoralen.

Psoralens are lipophilic molecules used to treat skin diseases such as vitiligo and psoriasis, among them, 8-Methoxypsoralen (8-MOP) is the most used to topical skin application. Topical treatment with psoralens can be limited due to insufficient drug penetration into the skin layers. Nanoemulsions have attracted much attention due to their as dermal delivery systems for lipophilic drugs such as 8-MOP. However, nanoemulsions feature low viscosity, which might be unsuitable for topical application. In this work, we produced hydrogel-thickened nanoemulsions using chitosan with different molecular weight as thickening polymer to overcome the low viscosity attributed to nanoemulsions. The aim of this study is to characterize oil-in-water (o/w) nanoemulsions and hydrogel-thickened nanoemulsions based on two different essential oils to in vitro controlled release of 8-MOP. In a previous work, we have reported production, stability and in vitro transdermal release of such formulations. Here, 8-MOP loaded nanoemulsions and hydrogel-thickened nanoemulsions were characterized regarding their morphology, rheological behavior, and in vitro drug release kinetics. Hydrogel-based systems presented a gel-like rheological behavior, being classified as weak gels. 8-MOP in vitro release from hydrogels-based formulations using clove essential oil showed strong dependency chitosan molecular weight. On the other hand, hydrogel-thickened nanoemulsions using sweet fennel oil as inner phase, showed an unexpected pH-dependent behavior not fully understood at the moment. These results need further investigation, nevertheless hydrogel-thickened nanoemulsions revealed to be interesting and complex dermal delivery systems for poorly soluble drugs.

Dual alginate-lipid nanocarriers as oral delivery systems for amphotericin B.

Amphotericin B (AmB) is the first-choice drug to treat several fungal infections. However, due to its low solubility it can only be administrated intravenously. Nanostructured lipid carriers (NLC) have the ability to encapsulate hydrophobic drugs in an aqueous matrix, making them interesting for use in alternative drug delivery systems for AmB. Their combination with stimuli-sensitive polymers such as alginate can be used as a strategy to protect acid sensitive molecules from gastric acid. The proposal of this work was to develop a dual-strategy hydrogel/NLC delivery system for amphotericin B. NLCs were produced by high-pressure homogenization and their size and stability were assessed by dynamic light scattering and electron transmission microscopy. The NLCs presented low cytotoxicity and high selectivity at neutral pH. Alginate hydrogels were successfully produced by the ionic gelation method and characterized using optical microscopy. The hydrogels were tested for their pH-selectivity, cytotoxicity and drug delivery profile. Swelling degree and drug delivery profiles suggested that drug delivery is stimulated as the alginate particles swell and that NLC particles maintain their structure even after rehydration, indicating these systems can be used for oral delivery of AmB.

Hydrogel-thickened nanoemulsions based on essential oils for topical delivery of psoralen: Permeation and stability studies.

Nanoemulsions (NE) have attracted much attention due to their as dermal delivery systems for lipophilic drugs such as psoralens. However, NE feature low viscosity which might be unsuitable for topical application. In this work, we produced hydrogel-thickened nanoemulsions (HTN) using chitosan as thickening polymer to overcome the low viscosity attributed to NE. The aim of this study is to develop and characterize oil-in-water (o/w) HTN based on sweet fennel and clove essential oil to transdermal delivery of 8-methoxsalen (8-MOP). NE components (oil, surfactant) were selected on the basis of solubility and droplet size and processed in a high-pressure homogenizer (HPH). Drug loaded NE and HTN were characterized for particle size, stability under storage and centrifugation, rheological behavior, transdermal permeation and skin accumulation. Transdermal permeation of 8-MOP from HTN was determined by using Franz diffusion cell. Transdermal permeation from HTN using clove essential oil showed strong dependency chitosan molecular weight. On the other hand, HTN using sweet fennel oil showed an unexpected pH-dependent behavior not fully understood at the moment. These results need further investigation, nevertheless HTN revealed to be interesting and complex dermal delivery systems for poorly soluble drugs.

Polymer-based Drug Delivery Systems Applied to Insects Repellents Devices: A Review.

Insects-borne diseases constitute a public health concern. Since there is no vaccine or curative treatment for many of these diseases, individual protection is the main approach to prevent them. Nowadays, the search for replacing synthetic molecules for insect repellents from natural sources, such as essential oils, is increasing. However, most of them present low efficiency compared to synthetic repellents. Therefore, decreasing skin permeation of synthetic repellents or yet, increasing effectiveness of natural repellents are challenges that must be overcome during the development of novel insect repellent formulations. In this context, polymer-based formulations allow entrapping active ingredients and provide release control. Encapsulation into polymeric micro/nanocapsules, cyclodextrins, polymeric micelles or hydrogels constitutes an approach to modify physicochemical properties of encapsulated molecules. Such techniques, applied in topical formulations, fabrics modification for personal protection, or food packaging have proved to be more effective in increasing repellency time and also in reducing drug dermal absorption, improving safety profiles of these products. In this work, the main synthetic and natural insect repellents are described as well as their polymeric carrier systems and their potential applications.

Development and characterization of micellar systems for application as insect repellents.

N,N-diethyl-meta-toluamide (DEET) is a widely used insect repellent due to its high efficacy. In this work, micellar systems based on poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer were developed and studied for the purpose of controlling the release and cutaneous permeation of DEET, using concentrated solutions of the copolymer Pluronic F127 to form thermoreversible gels. The formulations presented thermoreversible gelation above 5°C and altered rheological behavior at 15 and 25°C. The presence of the drug drastically changed the sol-gel transition temperatures. The micrographs suggest that DEET induced the formation of anisotropic structures, and Maltese Crosses were observed. The formulation containing 10wt% DEET and 15wt% Pluronic F127 presented sustained drug release for up to 7h. DEET release profile followed the Higuchi kinetics model. There was a reduction of approximately 35% in the amount of DEET absorbed through the skin after 6h. About 62% of DEET from the formulation consisting of Pluronic F127 and DEET remain retained on the skin. The anisotropic structure may constitute a barrier to diffusion and thereby controlling the drug release effectively. These tests suggest that the tested samples exhibit safety profile greater than some commercially available products.