Insights into the bioactive potential of the Amazonian species Acmella oleracea leaves extract: A focus on wound healing applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Acmella oleracea is traditionally used by Amazonian folks to treat skin and mucous wounds, influenza, cough, toothache, bacterial and fungal infections. Its phytoconstituents, such as alkylamides, phenolic compounds, and terpenes, are reported to produce therapeutic effects, which justify the medicinal use of A. oleracea extracts. However, the scientific evidence supporting the application A. oleracea bioactive products for wound treatment of remains unexplored so far. OBJECTIVE: This work aimed to characterize the phytochemical composition of methanolic extract of A. oleracea leaves (AOM) and to investigate their antioxidant, anti-inflammatory, antimicrobial and healing potential focusing on its application for wound healing. MATERIAL AND METHODS: The dried leaves from A. oleracea submitted to static maceration in methanol for 40 days. The phytochemical constitution of AOM was analyzed based on the total phenolic dosage method and by UFLC-QTOF-MS analysis. Antioxidant activity was assessed by DPPH and NO scavenging activities, as well as MDA formation, evaluation of ROS levels, and phosphomolybdenum assays. In vitro anti-inflammatory activities were assessed by reduction of NO, IL-6, and TNF-α production and accumulation of LDs in peritoneal macrophages cells. Antimicrobial activity was evaluated by determining MIC and MBC/MFC values against P. aeruginosa, E. coli, S. epidermidis, S. aureus and C. albicans, bacterial killing assay, and biofilm adhesion assessment. In vitro wound healing activity was determined by means of the scratch assay with L929 fibroblasts. RESULTS: Vanillic acid, quercetin, and seven other alkamides, including spilanthol, were detected in the UFLC-QTOF-MS spectrum of AOM. Regarding the biocompatibility, AOM did not induce cytotoxicity in L929 fibroblasts and murine macrophages. The strong anti-inflammatory activity was evidenced by the fact that AOM reduced the cellular production of inflammatory mediators IL-6, TNF-α, NO, and LDs in macrophages by 100%, 96.66 ± 1.95%, 99.21 ± 3.82%, and 67.51 ± 0.72%, respectively. The antioxidant effects were confirmed, since AOM showed IC50 values of 44.50 ± 4.46 and 127.60 ± 14.42 µg/mL in the DPPH and NO radical inhibition assays, respectively. Additionally, AOM phosphomolybdenium reducing power was 63.56 ± 13.01 (RAA% of quercetin) and 104.01 ± 21.29 (RAA% of rutin). Finally, in the MDA quantification assay, AOM showed 63,69 ± 3.47% of lipid peroxidation inhibition. It was also observed that the production of ROS decreased by 69.03 ± 3.85%. The MIC values of AOM ranged from 1000 to 125 µg/mL. Adhesion of S. aureus, P. Aeruginosa, and mixed biofilms was significantly reduced by 44.71 ± 4.44%, 95.50 ± 6.37 %, and 51.83 ± 1.50%, respectively. AOM also significantly inhibited the growth of S. aureus (77.17 ± 1.50 %) and P. aeruginosa (62.36 ± 1.01%). Furthermore, AOM significantly enhanced the in vitro migration of L929 fibroblasts by 97.86 ± 0.82% compared to the control (P < 0.05). CONCLUSIONS: This study is the first to report total antioxidant capacity and intracellular LD reduction by AOM. The results clearly demonstrated that AOM exerts potent anti-inflammatory, antioxidant, antimicrobial, and wound healing effects, encouraging its further investigation and promising application in wound treatment.

Exploring the antimicrobial efficacy of tea tree essential oil and chitosan against oral pathogens to overcome antimicrobial resistance.

BACKGROUND: Considering that antimicrobial resistance among oral pathogens is a significant concern in dental practice, with broader implications for overall health due to the oral microbiota serving as a reservoir for antibiotic resistance genes (ARGs), research into natural products is crucial for addressing this issue. OBJECTIVE: This study aimed to evaluate tea tree oil (TTO) and chitosan (CH) performance against oral pathogens, including mixed-species biofilm, and its effects on bacteria growth, in addition to chemical characterization and cytotoxicity of TTO. METHODS: Tea Tree Oil and low molecular weight chitosan were used in this study. The chemical composition of TTO was analyzed using gas chromatography coupled with mass spectrometry (GC-MS). To evaluate TTO's antimicrobial properties, time-kill and cell viability assays were conducted. Additionally, minimum inhibitory concentration (MIC), minimum microbiocidal concentration (MMC), checkerboard, and biofilm assays were performed using TTO and CH alone and in combination. RESULTS: TTO chromatography peaks found consistent with the standard ISO4730:2017 and literature. TTO and CH exhibited inhibitory activity against all tested microorganisms. The predominantly microbiostatic activity of TTO is probably related to terpinen-4-ol associated with terpinene. The oil at MIC value was able to delay the log phase of Aggregatibacter actinomycetemcomitans growth. Fibroblasts (L929) viability remained above 70 % during 24 h for TTO concentrations ranging from 0.5 to 0.0625 mg/ml. TTO-CH combination showed a synergistic activity (FIC = 0.5) against A. actinomycetemcomitans and Streptococcus sanguinis, at a concentration of 0,25MIC for both species. The compounds at MIC concentration inhibited both monospecies and mixed-species biofilms studied bacteria to the same extent as the azithromycin control. CONCLUSION: TTO and CH demonstrated efficacy in combating oral pathogens and TTO-CH combination offers a promising approach to confront microbial resistance in the oral environment.

Novel natural lipids based NLC containing finasteride improved androgenetic alopecia treatment in rats.

Androgenetic alopecia (AGA) is the most common hair loss disorder, affecting millions of men and women worldwide. Current formulations used to treat this condition often lead to a wide variety of side effects, ranging from allergies to sexual disfunction, especially when those drugs are administered orally. In this study, we developed and tested unique formulations containing nanostructured lipid carriers (NLC) composed of lipids extracted from fruit seeds, carrying finasteride to enhance efficacy of AGA treatment. By stabilizing the hydrophobic compounds in the solid matrix, three formulations of NLC were engineered and successfully prepared. Further an in vivo model of AGA was induced in rats by the administration of testosterone, as a platform to evaluate the efficiency of the formulations. The chosen formulation exhibited high bioavailability, medium size of 124.5 nm and PdI of 0.143, without systemic absorption. In addition, it promoted efficient and significant follicle restoration in AGA induced rats by increasing number of active bulbs and showed to be a safe formulation for topical application. The results of this research indicate that the presented formulation has significant potential to yield improved outcomes in AGA treatment.

Combined potential of copaifera officinalis oleoresin and chitosan against oral pathogens.

Copaifera officinalis Oleoresin (COR) and Chitosan (CH) were combined to test the potential to inhibit oral bacteria. First, COR was analyzed by GC-MS to identify its main constituents and then Minimum Inhibitory Concentration (MIC) assays and Minimum Microbiocidal Concentration (MMC) of the compounds alone against 17 pathogens were performed. Sixteen primary compounds were identified in COR, but the major constituent was ß-Caryophyllene (40.5%). COR showed MIC concentrations of 26.04 to 46.87 µg/mL and CH 0.1 mg/mL to 0.8 mg/mL. Second, the combination against oral bacteria strains was tested using a checkerboard test with the determination of Fractional Inhibitory Concentration (FIC) for synergistic effect, followed by the bacterial biofilm aggregation test using monospecies and mixed biofilm. The combination of COR and CH showed a synergistic effect for S. oralis (ATCC 10557) and an additive effect for the other strains tested, promoting bactericidal activity, as well as reducing the concentrations needed to cause bacterial inhibition. In addition, it showed good activity in inhibiting biofilm formation, with inhibition percentages close to Azithromycin. The results of this study highlight the synergistic potential of COR and CH combination as a promising strategy in the search for innovative antimicrobial therapies for infections related to oral bacterial biofilms.

The Role of Inhaled Chitosan-Based Nanoparticles in Lung Cancer Therapy.

Lung cancer is the leading cause of cancer-related mortality worldwide, largely due to the limited efficacy of anticancer drugs, which is primarily attributed to insufficient doses reaching the lungs. Additionally, patients undergoing treatment experience severe systemic adverse effects due to the distribution of anticancer drugs to non-targeted sites. In light of these challenges, there has been a growing interest in pulmonary administration of drugs for the treatment of lung cancer. This route allows drugs to be delivered directly to the lungs, resulting in high local concentrations that can enhance antitumor efficacy while mitigating systemic toxic effects. However, pulmonary administration poses the challenge of overcoming the mechanical, chemical, and immunological defenses of the respiratory tract that prevent the inhaled drug from properly penetrating the lungs. To overcome these drawbacks, the use of nanoparticles in inhaler formulations may be a promising strategy. Nanoparticles can assist in minimizing drug clearance, increasing penetration into the lung epithelium, and enhancing cellular uptake. They can also facilitate increased drug stability, promote controlled drug release, and delivery to target sites, such as the tumor environment. Among them, chitosan-based nanoparticles demonstrate advantages over other polymeric nanocarriers due to their unique biological properties, including antitumor activity and mucoadhesive capacity. These properties have the potential to enhance the efficacy of the drug when administered via the pulmonary route. In view of the above, this paper provides an overview of the research conducted on the delivery of anticancer drug-loaded chitosan-based nanoparticles incorporated into inhaled drug delivery devices for the treatment of lung cancer. Furthermore, the article addresses the use of emerging technologies, such as siRNA (small interfering RNA), in the context of lung cancer therapy. Particularly, recent studies employing chitosan-based nanoparticles for siRNA delivery via the pulmonary route are described.

Anti-Inflammatory Activity and Acute Toxicity Of Pereskia aculeata, In Zophobas morio Larvae.

Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol (ß-SIT) and stigmasterol (STIG). The objective of the study was to evaluate the anti-inflammatory and toxicity activities of the hexane partition of P. aculeata (PHEX), as well as ß-SIT and STIG. PHEX was prepared and the phytosterols were quantified. In terms of toxicity against L929 fibroblast cells, PHEX showed toxicity up to 200 µg/mL; STIG and ß-SIT showed toxicity up to 25 µg/mL. PHEX inhibited 66 % of nitric oxide radicals, while STIG and ß-SIT inhibited 33.73 % and 34.94 %, respectively. In an anti-inflammatory test against Zophobas morio larvae, all samples significantly reduced hemocyte levels. Additionally, the LD50 values were calculated: 229.6 mg/kg for PHEX, 101.5 mg/kg for STIG, and 103.8 mg/kg for ß-SIT. In conclusion, the study indicates that the phytosterols present in PHEX may contribute to its anti-inflammatory activity.

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.

Advancements in Chitosan-Based Nanoparticles for Pulmonary Drug Delivery.

The evolution of respiratory diseases represents a considerable public health challenge, as they are among the leading causes of death worldwide. In this sense, in addition to the high prevalence of diseases such as asthma, chronic obstructive pulmonary disease, pneumonia, cystic fibrosis, and lung cancer, emerging respiratory diseases, particularly those caused by members of the coronavirus family, have contributed to a significant number of deaths on a global scale over the last two decades. Therefore, several studies have been conducted to optimize the efficacy of treatments against these diseases, focusing on pulmonary drug delivery using nanomedicine. Thus, the development of nanocarriers has emerged as a promising alternative to overcome the limitations of conventional therapy, by increasing drug bioavailability at the target site and reducing unwanted side effects. In this context, nanoparticles composed of chitosan (CS) show advantages over other nanocarriers because chitosan possesses intrinsic biological properties, such as anti-inflammatory, antimicrobial, and mucoadhesive capacity. Moreover, CS nanoparticles have the potential to enhance drug stability, prolong the duration of action, improve drug targeting, control drug release, optimize dissolution of poorly soluble drugs, and increase cell membrane permeability of hydrophobic drugs. These properties could optimize the performance of the drug after its pulmonary administration. Therefore, this review aims to discuss the potential of chitosan nanoparticles for pulmonary drug delivery, highlighting how their biological properties can improve the treatment of pulmonary diseases, including their synergistic action with the encapsulated drug.

Kaurenoic acid nanocarriers regulates cytokine production and inhibit breast cancer cell migration.

Breast cancer is the type of cancer with the highest incidence in women around the world. Noteworthy, the triple-negative subtype affects 20% of the patients while presenting the highest death rate among subtypes. This is due to its aggressive phenotype and the capability of invading other tissues. In general, tumor-associated macrophages (TAM) and other immune cells, are responsible for maintaining a favorable tumor microenvironment for inflammation and metastasis by secreting several mediators such as pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α, chemokines like CCL2, and other proteins, as metalloproteinases of matrix (MMP). On the other hand, immunomodulatory agents can interfere in the immune response of TAM and change the disease prognosis. In this work, we prepared nanostructured lipid carriers containing kaurenoic acid (NLC-KA) to evaluate the effect on cytokine production in vitro of bone marrow-derived macrophages (BMDM) and the migratory process of 4 T1 breast cancer cells. NLC-KA prepared from a blend of natural lipids was shown to have approximately 90 nm in diameter with low polydispersity index. To test the effect on cytokine production in vitro in NLC-KA treated BMDM, ELISA assay was performed and pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α were quantified. The formulation reduced the secretion of IL-1ß and TNF-α cytokines while presenting no hemolytic activity. Noteworthy, an anti-migratory effect in 4 T1 breast cancer cells treated with NLC-KA was observed in scratch assays. Further, MMP9 and CCL2 gene expressions in both BMDM and 4 T1 treated cells confirmed that the mechanism of inhibition of migration is related to the blockade of this pathway by KA. Finally, cell invasion assays confirmed that NLC-KA treatment resulted in less invasiveness of 4 T1 cells than control, and it is independent of CCL2 stimulus or BMDM direct stimulus. Ultimately, NLC-KA was able to regulate the cytokine production in vitro and reduce the migration of 4 T1 breast cancer cells by decreasing MMP9 gene expression.

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.

Cecropia pachystachya Trécul: a promising ingredient for skin-whitening cosmetics

Abstract Because it promotes the lightening of pigment spots, tyrosinase inhibition is one of the mechanisms of depigmenting cosmetic products. Considering the adverse effects produced by synthetic depigmenting actives, the search for new therapeutic options is desirable, and plant extracts are possible candidates for hyperpigmentation treatment. Glycolic extracts of Cecropia pachystachya Trécul are, therefore, the focus of this study. Its chemical characterization, antioxidant activity, tyrosinase inhibition, and cell viability were evaluated. Glycolic extracts were obtained by macerating the leaves of C. pachystachya in grain alcohol and glycerin or propylene glycol. Both had a similar chemical constitution, the glycerin being more efficient in concentrating phenolic compounds and flavonoids. Analyses by UHPLC-MS detected quinic acid, chlorogenic acid isomers, proanthocyanidin dimers type B and C, catechin/epicatechin, orientin/isoorientin, isoorientin 2"-O-xyloside, vitexin/isovitexin, and rutin. 5-O-caffeoylquinic acid was then quantified was then quantified, with predominance in the extract produced with propylene glycol. These extracts showed a high antioxidant capacity by the method of DPPH, ß-carotene, and nitric oxide. As for depigmenting activity, both extracts were able to inhibit tyrosinase. Cell viability assay also revealed that the extracts could safely be used in concentrations of ≤ 125 µg/mL. Thus, this study demonstrated for the first time that the glycolic extracts of C. pachystachya have promising chemical and biological characteristics for the development of a multifunctional cosmetic with antioxidant and tyrosinase-inhibition activities

Nanostructured Lipid Carriers for the Formulation of Topical Anti-Inflammatory Nanomedicines Based on Natural Substances.

The main function of the skin is to protect the body from the external environment. However, the skin can undergo inflammatory processes, due to genetic, hormonal, or environmental factors. When the defense system is overloaded, there is an increase in pro-inflammatory mediators and reactive oxygen species (ROS), which results in skin disorders. Among the substances used to treat these inflammatory processes, many natural substances with anti-inflammatory and antioxidant properties are being studied: nature is yet an abundant source to obtain diverse pharmacological actives. The treatment of skin diseases is usually focused on topical application, as it reduces the risk of systemic side effects and prevents drug degradation by first-pass metabolism. Thus, the properties of drug delivery vehicles can facilitate or inhibit its permeation. Due to the hydrophobic nature of the skin, a promising strategy to improve dermal drug penetration is the use of lipid-based nanoparticles, such as nanostructured lipid carriers (NLC). Therefore, in this review, we present NLC as a tool to improve dermal administration of natural substances with anti-inflammatory properties.

Pharmacological investigation of antioxidant and anti-inflammatory activities of leaves and branches extracts from Plinia cauliflora (Jaboticaba).

ETHNOPHARMACOLOGICAL RELEVANCE: Among all native Brazilian plant species, Plinia cauliflora (DC.) Kausel (Jaboticaba), is well known for producing "superfruits", due to their high phenolic content and antioxidant property. The fruit has astringent characteristics, and it is popularly known for the treatment of diarrhea, rash, and intestinal inflammation. However, there are only a few studies on the use of leaves and branches of this species in the literature, mainly to treat oxidative stress and inflammation. AIM OF THE STUDY: The present study aimed to investigate the antioxidant and anti-inflammatory potential of leaves and branches extracts from P. cauliflora. MATERIAL AND METHODS: The phytochemical analysis of P. cauliflora extracts was performed by the total phenolic, flavonoid, and tannin dosage method. Moreover, the compounds were identified by HPLC-MS-Q-TOF. Antioxidant capacity was determined by DPPH, ß-carotene/linoleic acid system, MDA formation, and phosphomolybdenum assays. In vitro and in vivo anti-inflammatory activities of P. cauliflora were evaluated by the reduction of nitric oxide in the J774A.1 cell line and inhibition of ear edema in mice, respectively. RESULTS: The ethanolic extract of the leaves exhibited greater flavonoid content whereas the ethanolic extract of the branches showed higher tannins content. Twenty-two and seventeen compounds were identified by HPLC-MS-Q-TOF in the leaves and branches, respectively, being tellimagrandin I, castalagin, and valoneic acid dilactone reported for the first time in P. cauliflora. The antioxidant potential of extracts was confirmed through different oxidation pathways from oxidizing radicals, which might be related to the presence of phenolic compounds. For the anti-inflammatory assay, the leaves and branches extracts showed promising results, with a reduction of nitric oxide ear edema inhibition around 95% and 80%, respectively. CONCLUSIONS: Herein, the great biological potential of leaves and branches extracts from P. cauliflora was highlighted. These parts of the plant are underused and poorly reported in the literature, especially for the antioxidant and anti-inflammatory activities.

Improved anti-Cutibacterium acnes activity of tea tree oil-loaded chitosan-poly(ε-caprolactone) core-shell nanocapsules.

The purpose of this study was to develop tea tree oil (TTO)-loaded chitosan-poly(ε-caprolactone) core-shell nanocapsules (NC-TTO-Ch) aiming the topical acne treatment. TTO was analyzed by gas chromatography-mass spectrometry, and nanocapsules were characterized regarding mean particle size (Z-average), polydispersity index (PdI), zeta potential (ZP), pH, entrapment efficiency (EE), morphology by Atomic Force Microscopy (AFM), and anti-Cutibacterium acnes activity. The main constituents of TTO were terpinen-4-ol (37.11 %), γ-terpinene (16.32 %), α-terpinene (8.19 %), ρ-cimene (6.56 %), and α-terpineol (6.07 %). NC-TTO-Ch presented Z-average of 268.0 ± 3.8 nm and monodisperse size distribution (PdI < 0.3). After coating the nanocapsules with chitosan, we observed an inversion in ZP to a positive value (+31.0 ± 1.8 mV). This finding may indicate the presence of chitosan on the nanocapsules' surface, which was corroborated by the AFM images. In addition, NC-TTO-Ch showed a slightly acidic pH (∼5.0), compatible with topical application. The EE, based on Terpinen-4-ol concentration, was approximately 95 %. This data suggests the nanocapsules' ability to reduce the TTO volatilization. Furthermore, NC-TTO-Ch showed significant anti-C. acnes activity, with a 4× reduction in the minimum inhibitory concentration, compared to TTO and a decrease in C. acnes cell viability, with an increase in the percentage of dead cells (17 %) compared to growth control (6.6 %) and TTO (9.7 %). Therefore, chitosan-poly(ε-caprolactone) core-shell nanocapsules are a promising tool for TTO delivery, aiming at the activity against C. acnes for the topical acne treatment.

N,N,N-trimethylchitosan-poly (n-butylcyanoacrylate) core-shell nanoparticles as a potential oral delivery system for acyclovir.

This study investigated the feasibility of polysaccharide-coated poly(n-butyl cyanoacrylate) (PBCA) nanoparticles for oral delivery of acyclovir (ACV). PBCA nanoparticles were obtained by the emulsion polymerization method. Chitosan was chemically modified to obtain N,N,N-trimethylchitosan (TMC), which was used to coat the nanoparticles (PBCA-TMC). Nanoparticles were characterized by dynamic light scattering, zeta potential, differential scanning calorimetry (DSC), atomic force microscopy (AFM), cytotoxicity, and the effect on the transepithelial electrical resistance (TEER) of the Caco-2 cells. The size of the coated nanoparticles (296.2 nm) was significantly larger than uncoated (175.0 nm). Furthermore, PBCA nanoparticles had a negative charge (-11.7 mV), which was inverted to highly positive values (+36.5 mV) after coating. DSC analysis suggested the occurrence of the coating, which was confirmed by AFM images. The MTT assay revealed concentration-dependent cytotoxicity for the core-shell nanoparticles. Additionally, PBCA-TMC caused a significant but reversible decrease in the Caco-2 cell monolayer TEER. Entrapped ACV (PBCA-ACV-TMC), a Biopharmaceutical Classification System class III drug substance, increased approximately 3.25 times the Papp of ACV in the Caco-2 permeability assay. The nanoparticles were also able to provide in vitro ACV controlled release using media with different pH values (1.2; 6.8; 7.4). Accordingly, this new core-shell nanoparticle showed the potential to improve the oral delivery of ACV.

Development and in vivo evaluation of chitosan-gel containing Mitracarpus frigidus methanolic extract for vulvovaginal candidiasis treatment.

Vulvovaginal candidiasis (VVC) is characterized by inflammatory changes in the vaginal mucosa caused by abnormal colonization of Candida species. Traditional topical therapies using reference antifungal drugs usually present several issues and limitations for VVC treatment. Thus, the interest in new vaginal formulations, mainly those based on compounds from natural origin, has been growing over the last years. Methanolic extract from the plant species Mitracarpus frigidus (Willd. Ex Reem Schult.) K. Schum (MFM) has presented potential antifungal activity against C. albicans vaginal infection. Here, we aimed to develop and characterize a gynecological gel formulation based on chitosan containing MFM and to evaluate its anti-C. albicans effectiveness in the treatment of VVC. First, MFM was incorporated into a gel formulation based on chitosan in three final concentrations: 2.5 %, 5.0 %, and 10.0 %. Next, these gel formulations were subjected to stationary and oscillatory rheological tests. Finally, the gel was tested in an experimental VVC model. The rheological tests indicated pseudoplastic fluids, becoming more viscous and elastic with the increase of the extract concentration, indicating intermolecular interactions. Our in vivo analyses demonstrated a great reduction of vulvovaginal fungal burden and infection accompanied with the reduction of mucosal inflammation after MFM chitosan-gel treatment. The present findings open perspectives for the further use of the MFM-chitosan-gel formulation as a therapeutic alternative for VVC treatment.

Biodegradable nanocarriers coated with polymyxin B: Evaluation of leishmanicidal and antibacterial potential.

Most treatments of leishmaniasis require hospitalization and present side effects or parasite resistance; innovations in drug formulation/reposition can overcome these barriers and must be pursued to increase therapeutic alternatives. Therefore, we tested polymyxin B (polB) potential to kill Leishmania amazonensis, adsorbed or not in PBCA nanoparticles (PBCAnp), which could augment polB internalization in infected macrophages. PBCAnps were fabricated by anionic polymerization and analyzed by Dynamic Light Scattering (size, ζ potential), Nanoparticle Tracking Analysis (size/concentration), vertical diffusion cell (release rate), drug incorporation (indirect method, protein determination) and in vitro cell viability. Nanoparticles coated with polB (PBCAnp-polB) presented an adequate size of 261.5 ± 25.9 nm, low PDI and ζ of 1.79 ± 0.17 mV (stable for 45 days, at least). The 50% drug release from PBCAnp-polB was 6-7 times slower than the free polB, which favors a prolonged and desired release profile. Concerning in vitro evaluations, polB alone reduced in vitro amastigote infection of macrophages (10 µg/mL) without complete parasite elimination, even at higher concentrations. This behavior limits its future application to adjuvant leishmanicidal therapy or antimicrobial coating of carriers. The nanocarrier PBCAnp also presented leishmanicidal effect and surpassed polB activity; however, no antimicrobial activity was detected. PolB maintained its activity against E. coli, Pseudomonas and Klebsiella, adding antimicrobial properties to the nanoparticles. Thus, this coated drug delivery system, described for the first time, demonstrated antileishmanial and antimicrobial properties. The bactericidal feature helps with concomitant prevention/treatment of secondary infections that worst ulcers induced by cutaneous L. amazonensis, ultimately ending in disfiguring or disabling lesions.

Effects of nanoemulsions prepared with essential oils of copaiba- and andiroba against Leishmania infantum and Leishmania amazonensis infections.

Plant products are an important source of bioactive agents against parasitic diseases, including leishmaniasis. Among these products, vegetable oils have gained ground in the pharmaceutical field. Here we report the development of nanoemulsions as a delivery system for copaiba and andiroba oils (nanocopa and nanoandi) in order to test their effects on Leishmania infantum and L. amazonensis. The nanocopa and nanoandi had an average particle size of 76.1 and 88.1, respectively with polydispersity index 0.14 to 0.16 and potential zeta -2.54 to -3.9. The data indicated toxic activity of nanocopa and nanoandi against promastigotes of both Leishmania species ultrastructural analyses by scanning electron microscopy revealed that exposition to nanoemulsions induced oval cell shape and retracted flagella. The treatment with nanocopa and nanoandi led to a reduction in L. infantum and L. amazonensis infection levels in macrophage cultures. The nanoemulsions treatment have significant beneficial effects on all the parameters evaluated in lesions induced by L. amazonensis (lesion size, parasite burden and histopathology) on BALB/c mice. The treatment of L. infantum-infected BALB/c mice with nanoemulsions also showed promising results reducing parasite burden in spleen and liver and improving histopathological features.

Physical-chemical properties of furosemide nanocrystals developed using rotation revolution mixer.

Recently, several approaches have been reported to improve the dissolution rate and bioavailability of furosemide, a class IV drug. However, to the best of our knowledge, none of them proposed nanocrystals. In the last decade, nanocrystals successfully addressed solubility issues by increasing surface area and saturation solubility, both leading to an increase in the dissolution rate of poor water soluble drugs. The preparation of furosemide nanocrystals was by a rotation revolution mixer method. Size distribution and morphology were performed using laser diffraction and scanning electron microscopy, respectively. In addition, differential scanning calorimetry, thermogravimetry, X-ray powder diffraction (XRD) and low frequency shift-Raman spectroscopy allowed investigating the thermal properties and crystalline state. Solubility saturation and intrinsic dissolution rate (IDR) studies were conducted. The thermal analysis revealed lower melting range for the nanocrystals comparing to furosemide. Moreover, a slight crystalline structure change to the amorphous state was observed by XRD and confirmed by low frequency shift Raman. The particle size was reduced to 231 nm with a polydispersity index of 0.232, a 30-fold reduction from the original powder. Finally, the saturation solubility and IDR showed a significant increase. Furosemide nanocrystals showed potential for development of innovative formulations as an alternative to the commercial products.

The critical role of NIR spectroscopy and statistical process control (SPC) strategy towards captopril tablets (25 mg) manufacturing process understanding: a case study.

In this work, near-infrared spectroscopy (NIRS) method was used to evaluate the uniformity of dosage units of three captopril 25 mg tablets commercial batches. The performance of the calibration method was assessed by determination of Q value (0.9986), standard error of estimation (C-set SEE = 1.956), standard error of prediction (V-set SEP = 2.076) as well as the consistency (106.1%). These results indicated the adequacy of the selected model. The method validation revealed the agreement of the reference high pressure liquid chromatography (HPLC) and NIRS methods. The process evaluation using the NIRS method showed that the variability was due to common causes and delivered predictable results consistently. Cp and Cpk values were, respectively, 2.05 and 1.80. These results revealed a non-centered process in relation to the average target (100% w/w), in the specified range (85-115%). The probability of failure was 21:100 million tablets of captopril. The NIRS in combination with the method of multivariate calibration, partial least squares (PLS) regression, allowed the development of methodology for the uniformity of dosage units evaluation of captopril tablets 25 mg. The statistical process control strategy associated with NIRS method as PAT played a critical role in understanding of the sources and degree of variation and its impact on the process. This approach led towards a better process understanding and provided the sound scientific basis for its continuous improvement.