Search

Background: Acquired resistance and adverse effects are some of the challenges faced by thousands of Luminal A breast cancer patients under tamoxifen (TMX) treatment. Some authors associate the overexpression of HOXB7 with TMX resistance in this molecular subtype, and the knockdown of this gene could be an effective strategy to regain TMX sensitivity. Therefore, we used calcium phosphate hybrid nanoparticles (HNP) for the delivery of short interfering RNA molecule (siRNA) complementary to the HOXB7 gene and evaluated the RNA interference (RNAi) effects associated with TMX treatment in breast cancer in vivo. Methods: HNP were prepared by the self-assembly of a methoxy-poly (ethylene glycol)-block-poly (L-glutamic acid) copolymer (PEG-pGlu) and the coprecipitation of CaPO4 to incorporate siRNA. The in vitro cell viability and migration were evaluated prior to in vivo experiments. Further, animals bearing early-stage and advanced Luminal A breast cancer were treated with HNP-siHOXB7, HNP-siHOXB7 + TMX, and TMX. Antitumoral activity and gene expression were evaluated following histopathological, hematological, and biochemical analysis. Results: The HNP were efficient in delivering the siRNA in vitro and in vivo, whilst HOXB7 silencing associated with TMX administration promoted controlled tumor growth, as well as a higher survival rate and reduction in immuno- and hepatotoxicity. Conclusions: Therefore, our findings suggest that HOXB7 can be an interesting molecular target for Luminal A breast cancer, especially associated with hormone therapy, aiming for adverse effect mitigation and higher therapeutic efficacy. [ABSTRACT FROM AUTHOR]

As the cosmetic market continues to transform, innovative ingredients such as biosurfactants (BS) emerge as a fundamental step towards a generation of cosmetic products characterized by efficacy, safety, and environmental responsibility. In alignment with the global push towards natural, renewable, and non‐toxic materials, BS stands out as an interesting alternative to conventional synthetic surfactants. BS are a type of green surfactants and compared to synthetic surfactants derived from petroleum they are more biodegradable and have low or no toxicity. This work aimed to investigate the suitability of a biosurfactant extracted from the yeast Scheffersomyces shehatae (BS‐SS) to be used in cosmetic applications. The cytotoxicity of the BS‐SS was tested in fibroblast (L929) and keratinocyte (HaCaT) cell lines and the potential for ocular irritation was assessed by the hen's egg chorioallantoic membrane test (HET‐CAM). The cleaning efficiency of the BS‐SS was measured as the ability of make‐up removal in pig skin. Our results showed that the IC 50 values were 10.49 mg/mL for fibroblasts and 11.77 mg/mL for keratinocytes, and the biosurfactant did not result in hemorrhage, lysis, and coagulation damages in the chorioallantoic membrane, which classifies the biosurfactant solution as non‐irritant. Therefore, ocular toxicity and in vitro skin cell toxicity results showed that BS‐SS can be tolerable and safe for cosmetic purposes. BS‐SS featured promising cleaning properties, similar to the cleansing activity of the 1% SDS solution and of micellar water for lipstick and foundation products. In conclusion, the results indicate its potential use in cosmetic applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Breast cancer represents the most commonly diagnosed cancer worldwide, accounting for approximately one in eight cancers diagnosed. Despite significant advances in the diagnosis and detection of this disease, there is still a great need for more effective therapies to combat the invasive forms, especially those with a high incidence of metastasis. For that reason, bioactive molecules as peptides, including bovine lactoferricin (LfcinB), have been investigated. In this sense, there are reports that 20RRWQWR25 motif derivate from the LfcinB has shown activity against different cancer cell lines. Thus, current studies are being carried out with synthetic derivatives (linear, palindromic, dimer and tetrameric structures) that contain the 20RRWQWR25 motif in order to increase its activity against cancer cell lines by altering its hydrophobicity and net positive charge. In this regard, studies have focused on the use of LfcinB derivatives to combat breast cancer cell lines, with encouraging results. Therefore, in this mini-review, we present the state of the art regarding the activity of LfcinB and its analogs against breast cancer cell lines. [ABSTRACT FROM AUTHOR]

Many dermatological diseases still do not have an adequate treatment, such as melanoma. The treatments are usually lengthy, complex, with low cure rates and with severe side effects. This leads to low patient compliance, generating recurrence and/or worsening of the disease. Ethosomes, which are phospholipid-based vesicles containing ethanol, have shown great potential as drug delivery systems for the treatment of melanoma and other skin diseases. The unique structure of ethosomes allows for enhanced skin penetration and efficient delivery of therapeutic agents to the target site, improving the efficacy of treatment. The use of ethosomes in melanoma treatment holds promise for overcoming the limitations of conventional therapies, offering the potential for improved patient outcomes, reduced treatment duration, and minimized side effects. In this mini-review we present the advances, challenges, limitations and advantages, and future perspectives of the use of ethosomes in the treatment of the melanoma. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel nanostructured lipid carriers based on seed lipids were developed. • NLC containing finasteride was applied in vivo to treat androgenetic alopecia. • Increased active bulbs and hair restoration were observed in treated group. • Absence of systemic absorption and side effects after topical administration. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. aureu s 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. 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 IC 50 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). 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. [Display omitted] • Acmella oleracea extract exhibited no cytotoxic effects on L929 fibroblasts and murine macrophages. • A. oleracea extract significantly reduced the production of inflammatory mediators (IL-6, TNF-α, NO) by macrophages. • A. oleracea extract M demonstrated antioxidant activity by scavenging free radicals and inhibiting lipid peroxidation. • A. oleracea extract exhibited antimicrobial antibiofilm activities against various bacterial and fungal strains. • A. oleracea extract significantly enhanced the migration of fibroblasts in vitro , indicating its potential for wound healing. [ABSTRACT FROM AUTHOR]