RESUMO
Despite the promising potential of Solanum plant glycoalkaloids in combating skin cancer, their clinical trials have been halted due to dose-dependent toxicity and poor water solubility. In this study, we present a rational approach to address these limitations and ensure colloidal stability of the nanoformulation over time by designing solid lipid-polymer hybrid nanoparticles (SLPH). Leveraging the biocompatible and cationic properties of polyaspartamides, we employed a new polyaspartamide derivative (P1) as a raw material for this class of nanostructures. Subsequently, we prepared SLPH through a one-step process involving hot-melt emulsification followed by ultrasonication. The physicochemical properties of the SLPH were thoroughly characterized using dynamic light scattering (DLS), ζ-potential analysis, nanoparticle tracking analysis (NTA), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The optimized formulation exhibited long-term stability over six months under low temperatures, maintaining a particle size around 200â¯nm, a polydispersity index (PdI) lower than 0.2, and a ζ-potential between +35-40â¯mV. Furthermore, we evaluated the cytotoxic effect of the SLPH against human cutaneous melanoma cells (SK-MEL-28) compared to human foreskin fibroblast cells (HFF-1). Encapsulation of glycoalkaloids into the nanoparticles (SLPH-GE) resulted in a two-fold greater selective cytotoxic profile for melanoma cells than glycoalkaloids-free (GE). The nanoparticles disrupted the stratum corneum barrier with a penetration depth of approximately 77 µm. These findings underscore the potential of the developed nanosystem as an effective glycoalkaloid carrier with suitable colloidal and biological properties for further studies in topical treatment strategies for cutaneous melanoma.
Assuntos
Lipídeos , Melanoma , Nanopartículas , Polímeros , Humanos , Nanopartículas/química , Lipídeos/química , Melanoma/tratamento farmacológico , Melanoma/patologia , Polímeros/química , Polímeros/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Tamanho da Partícula , Alcaloides/química , Alcaloides/farmacologia , Linhagem Celular Tumoral , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Administração Tópica , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Propriedades de SuperfícieRESUMO
Brazilian green propolis is used in folk medicine because of its various biological properties. The hydroalcoholic extract of Brazilian green propolis is characteristic for possessing several pharmacological properties. Phytochemical investigations have attributed some of these properties to the presence of compounds, which were chosen as analytical markers. This paper reports the development and analytical validation using UPLC-MS/MS in MRM mode. Veratraldehyde was used as an internal standard in qualitative and quantitative analyses of the extracts. Relative standard deviation values obtained for intra-day and inter-day precision were lower than 4%. Of the five parameters for robustness, wavelength detection and flow rate were the critical ones. Limits of detection and quantification ranged from 0.300 to 39.500 ng.mL-1 and from 1.400 to 85.00 ng.mL-1, respectively. The recoveries were between 94.00 and 119.00%, with relative standard deviation values around 5.0%. The developed method is precise, sensitive, and reliable for analysing Brazilian green propolis.
RESUMO
We have evaluated eight p-coumaric acid prenylated derivatives inâ vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC50=45.92â µM) and S. mansoni (IC50=64.25â µM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives.
Assuntos
Antiprotozoários , Ácidos Cumáricos , Leishmania , Testes de Sensibilidade Parasitária , Schistosoma mansoni , Animais , Schistosoma mansoni/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/química , Leishmania/efeitos dos fármacos , Antiprotozoários/farmacologia , Antiprotozoários/química , Antiprotozoários/síntese química , Relação Estrutura-Atividade , Prenilação , Propionatos/farmacologia , Propionatos/química , Estrutura Molecular , Esquistossomicidas/farmacologia , Esquistossomicidas/química , Esquistossomicidas/síntese química , Relação Dose-Resposta a DrogaAssuntos
Nanopartículas , Própole , Própole/farmacologia , Leucócitos Mononucleares , Expressão Gênica , CitocinasRESUMO
The skin is essential to the integrity of the organism. The disruption of this organ promotes a wound, and the organism starts the healing to reconstruct the skin. Copaifera langsdorffii is a tree used in folk medicine to treat skin affections, with antioxidant and anti-inflammatory properties. In our study, the oleoresin of the plant was associated with nanostructured lipid carriers, aiming to evaluate the healing potential of this formulation and compare the treatment with reference drugs used in wound healing. Male Wistar rats were used to perform the excision wound model, with the macroscopic analysis of wound retraction. Skin samples were used in histological, immunohistochemical, and biochemical analyses. The results showed the wound retraction in the oleoresin-treated group, mediated by α-smooth muscle actin (α-SMA). Biochemical assays revealed the anti-inflammatory mechanism of the oleoresin-treated group, increasing interleukin-10 (IL-10) concentration and decreasing pro-inflammatory cytokines. Histopathological and immunohistochemical results showed the improvement of re-epithelialization and tissue remodeling in the Copaifera langsdorffii group, with an increase in laminin-γ2, a decrease in desmoglein-3 and an increase in collagen remodeling. These findings indicate the wound healing potential of nanostructured lipid carriers associated with Copaifera langsdorffii oleoresin in skin wounds, which can be helpful as a future alternative treatment for skin wounds.
Assuntos
Fabaceae , Reepitelização , Ratos , Animais , Ratos Wistar , Pele/patologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Fabaceae/química , LipídeosRESUMO
This study aimed at evaluating the potential of Copaifera lucens, specifically its oleoresin (CLO), extract (CECL), and the compound ent-polyalthic acid (PA), in combating caries and toxoplasmosis, while also assessing its toxicity. The study involved multiple assessments, including determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against cariogenic bacteria. CLO and PA exhibited MIC and MBC values ranging from 25 to 50 µg/mL, whereas CECL showed values equal to or exceeding 400 µg/mL. PA also displayed antibiofilm activity with minimum inhibitory concentration of biofilm (MICB50) values spanning from 62.5 to 1000 µg/mL. Moreover, PA effectively hindered the intracellular proliferation of Toxoplasma gondii at 64 µg/mL, even after 24 h without treatment. Toxicological evaluations included in vitro tests on V79 cells, where concentrations ranged from 78.1 to 1250 µg/mL of PA reduced colony formation. Additionally, using the Caenorhabditis elegans model, the lethal concentration (LC50) of PA was determined as 1000 µg/mL after 48 h of incubation. Notably, no significant differences in micronucleus induction and the NDI were observed in cultures treated with 10, 20, or 40 µg/mL of CLO. These findings underscore the safety profile of CLO and PA, highlighting their potential as alternative treatments for caries and toxoplasmosis.
RESUMO
Cancer incidence worldwide is alarming and among the cancers that affect women ovarian cancer is the most fatal. Many side effects are associated with conventional therapies and none of them are completely effective, so the development of new treatments is necessary. Brazilian red propolis extract is a natural product with complex composition and great potential for cancer treatment. However, its clinical application is harmed due to unfavourable physicochemical characteristics. To enable its application encapsulation in nanoparticles can be used. OBJECTIVES: The aims of this work were to develop polymeric nanoparticles with Brazilian red propolis extract and compare their action with the free extract against ovarian cancer cells. METHODS: Box Behnken design was used and nanoparticles were characterised using the techniques dynamic light scattering, nanoparticle tracking analysis, transmission electron microscopy, differential scanning calorimetry and encapsulation efficiency. Activity against OVCAR-3 was also tested on 2D and 3D models. KEY FINDINGS: Nanoparticles' sizes were ~200 nm with monomodal size distribution, negative zeta potential, spherical shape and with extract molecularly dispersed. Encapsulation efficiency was above 97% for the biomarkers chosen. Nanoparticles had greater efficacy in comparison with free propolis in OVCAR-3. CONCLUSIONS: So far, the nanoparticles here described have the potential to be a chemotherapy treatment in the future.
Assuntos
Nanopartículas , Neoplasias Ovarianas , Própole , Feminino , Humanos , Própole/farmacologia , Brasil , Apoptose , Neoplasias Ovarianas/tratamento farmacológico , Linhagem Celular Tumoral , Polímeros , Nanopartículas/química , BioensaioRESUMO
Helicobacter pylori is a Gram-negative, microaerophilic, curved-rod, flagellated bacterium commonly found in the stomach mucosa and associated with different gastrointestinal diseases. With high levels of prevalence worldwide, it has developed resistance to the antibiotics used in its therapy. Brazilian red propolis has been studied due to its biological properties, and in the literature, it has shown promising antibacterial activities. The aim of this study was to evaluate anti-H. pylori from the crude hydroalcoholic extract of Brazilian red propolis (CHEBRP). For this, in vitro determination of the minimum inhibitory and bactericidal concentration (MIC/MBC) and synergistic activity and in vivo, microbiological, and histopathological analyses using Wistar rats were carried out using CHEBRP against H. pylori strains (ATCC 46523 and clinical isolate). CHEBRP presented MIC/MBC of 50 and 100 µg/mL against H. pylori strains (ATCC 43526 and clinical isolate, respectively) and tetracycline MIC/MBC of 0.74 µg/mL. The association of CHEBRP with tetracycline had an indifferent effect. In the stomach mucosa of rats, all treatments performed significantly decreased the number of H. pylori, and a concentration of 300 mg/kg was able to modulate the inflammatory response in the tissue. Therefore, CHEBRP showed promising anti-H. pylori in in vitro and in vivo assays.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Própole , Ratos , Animais , Própole/farmacologia , Própole/uso terapêutico , Brasil , Ratos Wistar , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Imunidade , Tetraciclinas/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologiaRESUMO
Schistosomiasis mansoni is an infectious parasitic disease caused by worms of the genus Schistosoma, and praziquantel (PZQ) is the medication available for the treatment of schistosomiasis. However, the existence of resistant strains reinforces the need to develop new schistosomicidal drugs safely and effectively. Thus, the (±)-licarin A neolignan incorporated into poly-Æ-caprolactone (PCL) nanoparticles and not incorporated were evaluated for their in vivo schistosomicidal activity. The (±)-licarin A -loaded poly(ε-caprolactone) nanoparticles and the pure (±)-licarin A showed a reduction in the number of worm eggs present in spleens of mice infected with Schistosoma mansoni. In addition, the (±)-licarin A incorporated in the concentration of 20 mg/kg and 200 mg/kg reduced the number of worms, presenting percentages of 56.3% and 41.7%, respectively.
Assuntos
Nanopartículas , Esquistossomose mansoni , Esquistossomicidas , Animais , Caproatos , Lactonas , Lignanas , Camundongos , Poliésteres , Schistosoma mansoni , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia , Esquistossomicidas/farmacologia , Esquistossomicidas/uso terapêuticoRESUMO
Staphylococcus pseudintermedius is the leading cause of canine pyoderma. Honeybee products are common to treat this and other types of infections. High average annual population loss of bees has been observed. This study evaluated antibacterial and antibiofilm profile of Green Propolis and Baccharis dracunculifolia against S. pseudintermedius and the chemical similarities among both. Ethanolic extracts were produced and chemically characterized. The isolates were subjected to treatment with the extracts in both planktonic and sessile forms. Green propolis minimum inhibitory concentration (MIC) was 0.156 mg / mL, and minimum bactericidal concentration (MBC) was 0.312mg / mL. Baccharis dracunculifolia extract MIC and MBC was 0.312mg / mL and 2.5 mg / mL, respectivelly. Both extracts reduced SD55 formation of biofilm at minimum inhibitory concentration and at 1/8 minimum inhibitory concentration. The results observed in relation to ED99, were similar for both extracts. Besides that, similar chemical indicators between both extracts, including the presence of Artepellin C, suggest that the Baccharis dracunculifolia extract could be an alternative to the Green Propolis extract in the treatment of staph infections.