ABSTRACT
Background and aim: Tradescantia spathacea (T. spathacea) is a traditional medicinal plant from Central America and its tea, obtained by infusion, has been recognized as a functional food. The aim of this work was to investigate the effects of dry tea containing biocompounds from T. spathacea tea on motor and emotional behavior, as well as tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) expression in 6-hydroxydopamine (6-OHDA)-lesioned rats. Experimental procedure: Bioactives were identified by Ultra Performance Liquid Chromatography (UPLC) and an in vivo study in male Wistar rats was run as proof of concept of neuroprotective effects of DTTS. Results and conclusion: We found 15 biocompounds that had not been previously reported in T. spathacea: the UPLC-QTOF-MS/MS allowed identification five phenolic acids, one coumarin, two flavonoids, one iridoid, one phenylpropanoid glycoside, and six fatty acid derivatives. The dry tea of T. spathacea (DTTS) presented significant antioxidant activity and high contents of phenolic compounds and flavonoids. Doses of 10, 30, and 100 mg/kg of DTTS were protective against dopaminergic neurodegeneration and exhibited modulatory action on the astrocyte-mediated neuroinflammatory response. Behavioral tests showed that 30 mg/kg of DTTS counteracted motor impairment, while 100 mg/kg produced an anxiolytic effect. The DTTS could be, therefore, a promising strategy for the management of Parkinson's disease.
ABSTRACT
New wound dressings based on polymeric membranes have been widely exploited for clinical applications to assist in the healing process and prevent additional complications (e.g., bacterial infections). Here we propose the development of a new production method of polymeric membranes based on chitosan, incorporating glycolic extract of Aloe vera with joint synthesis of silver nanoparticles for use as a new bioactive dressing. The membranes were obtained by casting technique, and their morphological, physicochemical characteristics, degree of swelling, degradation profile and antimicrobial activity evaluated. Morphological analyzes confirmed the synthesis and presence of silver nanoparticles in the polymeric membrane. The chemical compatibility between the materials was demonstrated through thermal analysis (TGA and DSC) combined with ATR-FTIR tests, showing the complexation of the membranes (Mb-Ch-Ex.Av-NPs). All membranes were characterized as hydrophilic material (with a contact angle (Ó©) < 90°); however, the highest degree of swelling was obtained for the chitosan. (Mb-Ch) membrane (69.91 ± 5.75%) and the lowest for Mb-Ch-Ex.Av-NPs (26.62 ± 8.93%). On the other hand, the degradation profile was higher for Mb-Ch-Ex.Av-NPs (77.85 ± 7.51%) and lower for Mb-Ch (57.60 ± 2.29%). The manufactured bioactive dressings showed activity against Escherichia coli and Staphylococcus aureus. Our work confirmed the development of translucent and flexible chitosan-based membranes, incorporating Aloe vera glycolic extract with joint synthesis of silver nanoparticles for use as a new bioactive dressing, with proven antimicrobial activity.
ABSTRACT
Bixin is the main carotenoid found in the outer portion of the seeds of Bixa orellana L., commercially known as annatto. This compound is industrially employed in pharmaceutical, cosmetic, and food formulations as a natural dye to replace chemical additives. This study aimed to extract bixin from annatto seeds and obtain encapsulated bixin in a powder form, using freeze-drying encapsulation and maltodextrin as encapsulating agent. Bixin was extracted from annatto seeds employing successive washing with organic solvents, specifically hexane and methanol (1:1 v/v), followed by ethyl acetate and dichloromethane for subsequent washes, to effectively remove impurities and enhance bixin purity, and subsequent purification by crystallization, reaching 1.5 ± 0.2% yield (or approximately 15 mg of bixin per gram of seeds). Bixin was analyzed spectrophotometrically in different organic solvents (ethanol, isopropyl alcohol, dimethylsulfoxide, chloroform, hexane), and the solvents chosen were chloroform (used to solubilize bixin during microencapsulation) and hexane (used for spectrophotometric determination of bixin). Bixin was encapsulated according to a 22 experimental design to investigate the influence of the concentration of maltodextrin (20 to 40%) and bixin-to-matrix ratio (1:20 to 1:40) on the encapsulation efficiency (EE%) and solubility of the encapsulated powder. Higher encapsulation efficiency was obtained at a maltodextrin concentration of 40% w/v and a bixin/maltodextrin ratio of 1:20, while higher solubility was observed at a maltodextrin concentration of 20% w/v for the same bixin/maltodextrin ratio. The encapsulation of this carotenoid by means of freeze-drying is thus recognized as an innovative and promising approach to improve its stability for further processing in pharmaceutical and food applications.
ABSTRACT
Alternative splicing is the process of generating different mRNAs from the same primary transcript, which contributes to increase the transcriptome and proteome diversity. Abnormal splicing has been associated with the development of several diseases including cancer. Given that mutations and abnormal levels of the RIPK2 transcript and RIP-2 protein are frequent in tumors, and that RIP-2 modulates immune and inflammatory responses, we investigated alternative splicing events that result in partial deletions of the kinase domain at the N-terminus of RIP-2. We also investigated the structure and expression of the RIPK2 truncated variants and isoforms in different environments. In addition, we searched data throughout Supraprimates evolution that could support the biological importance of RIPK2 alternatively spliced products. We observed that human variants and isoforms were differentially regulated following temperature stress, and that the truncated transcript was more expressed than the long transcript in tumor samples. The inverse was found for the longer protein isoform. The truncated variant was also detected in chimpanzee, gorilla, hare, pika, mouse, rat, and tree shrew. The fact that the same variant has been preserved in mammals with divergence times up to 70 million years raises the hypothesis that it may have a functional significance.
Subject(s)
Alternative Splicing , Receptor-Interacting Protein Serine-Threonine Kinase 2 , Animals , Humans , Receptor-Interacting Protein Serine-Threonine Kinase 2/genetics , Receptor-Interacting Protein Serine-Threonine Kinase 2/metabolism , Evolution, Molecular , Protein Isoforms/genetics , Mice , Neoplasms/genetics , RatsABSTRACT
This analysis explores the principal regulatory concerns linked to nanomedicines and gene vaccines, including the complexities involved and the perspectives on how to navigate them. In the realm of nanomedicines, ensuring the safety of nanomaterials is paramount due to their unique characteristics and potential interactions with biological systems. Regulatory bodies are actively formulating guidelines and standards to assess the safety and risks associated with nanomedicine products, emphasizing the need for standardized characterization techniques to accurately gauge their safety and effectiveness. Regarding gene vaccines, regulatory frameworks must be tailored to address the distinct challenges posed by genetic interventions, necessitating special considerations in safety and efficacy evaluations, particularly concerning vector design, target specificity, and long-term patient monitoring. Ethical concerns such as patient autonomy, informed consent, and privacy also demand careful attention, alongside the intricate matter of intellectual property rights, which must be balanced against the imperative of ensuring widespread access to these life-saving treatments. Collaborative efforts among regulatory bodies, researchers, patent offices, and the private sector are essential to tackle these challenges effectively, with international cooperation being especially crucial given the global scope of nanomedicine and genetic vaccine development. Striking the right balance between safeguarding intellectual properties and promoting public health is vital for fostering innovation and ensuring equitable access to these ground-breaking technologies, underscoring the significance of addressing these regulatory hurdles to fully harness the potential benefits of nanomedicine and gene vaccines for enhancing healthcare outcomes on a global scale. STATEMENT OF SIGNIFICANCE: Several biomaterials are being proposed for the development of nanovaccines, from polymeric micelles, PLGA-/PEI-/PLL-nanoparticles, solid lipid nananoparticles, cationic lipoplexes, liposomes, hybrid materials, dendrimers, carbon nanotubes, hydrogels, to quantum dots. Lipid nanoparticles (LNPs) have gained tremendous attention since the US Food and Drug Administration (FDA) approval of Pfizer and Moderna's COVID-19 vaccines, raising public awareness to the regulatory challenges associated with nanomedicines and genetic vaccines. This review provides insights into the current perspectives and potential strategies for addressing these issues, including clinical trials. By navigating these regulatory landscapes effectively, we can unlock the full potential of nanomedicine and genetic vaccines using a range of promising biomaterials towards improving healthcare outcomes worldwide.
Subject(s)
Nanomedicine , Humans , Vaccines, DNA/adverse effectsABSTRACT
Among non-communicable diseases, cardiovascular diseases are the most prevalent, accounting for approximately 17 million deaths per year. Despite conventional treatment, cardiac tissue engineering emerges as a potential alternative for the advancement and treatment of these patients, using biomaterials to replace or repair cardiac tissues. Among these materials, gelatin in its methacrylated form (GelMA) is a biodegradable and biocompatible polymer with adjustable biophysical properties. Furthermore, gelatin has the ability to replace and perform collagen-like functions for cell development in vitro. The interest in using GelMA hydrogels combined with nanomaterials is increasingly growing to promote the responsiveness to external stimuli and improve certain properties of these hydrogels by exploring the incorporation of nanomaterials into these hydrogels to serve as electrical signaling conductive elements. This review highlights the applications of electrically conductive nanomaterials associated with GelMA hydrogels for the development of structures for cardiac tissue engineering, by focusing on studies that report the combination of GelMA with nanomaterials, such as gold and carbon derivatives (carbon nanotubes and graphene), in addition to the possibility of applying these materials in 3D tissue engineering, developing new possibilities for cardiac studies.
Subject(s)
Gelatin , Nanotubes, Carbon , Humans , Gelatin/chemistry , Tissue Scaffolds/chemistry , Nanotubes, Carbon/chemistry , Hydrogels/chemistry , Biocompatible Materials/chemistry , Tissue EngineeringABSTRACT
Inflammation is characterized by a biphasic cycle consisting initially of a proinflammatory phase that is subsequently resolved by anti-inflammatory processes. Interleukin-1ß (IL-1ß) is a master regulator of proinflammation and is encoded within the same topologically associating domain (TAD) as IL-37, which is an anti-inflammatory cytokine that opposes the function of IL-1ß. Within this TAD, we identified a long noncoding RNA called AMANZI, which negatively regulates IL-1ß expression and trained immunity through the induction of IL37 transcription. We found that the activation of IL37 occurs through the formation of a dynamic long-range chromatin contact that leads to the temporal delay of anti-inflammatory responses. The common variant rs16944 present in AMANZI augments this regulatory circuit, predisposing individuals to enhanced proinflammation or immunosuppression. Our work illuminates a chromatin-mediated biphasic circuit coordinating expression of IL-1ß and IL-37, thereby regulating two functionally opposed states of inflammation from within a single TAD.
Subject(s)
Chromatin , Inflammation , Humans , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-1beta/pharmacology , Chromatin/genetics , Inflammation/genetics , Inflammation/metabolism , Cytokines , Anti-Inflammatory Agents , Interleukin-1/metabolismABSTRACT
The aim of this work was to develop a dense lamellar scaffold, as a biomimetic material with potential applications in the regeneration of tracheal tissue after surgical tumor resection. The scaffolds were produced by plastic compression technique, exploiting the use of total phenolic compounds (TPC) from Psidium guajava Linn as a potential cross-linking agent in a polymeric mixture based on collagen (COL), silk fibroin (SF), and polyethylene glycol 400 (PEG 400). Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) confirmed the chemical interactions between the polymers and the cross-linking of TPC between COL and SF. Morphological analyses showed scaffolds with porosity, interconnectivity, and a porous surface structure with a gyroid-like geometry. The analysis of the anisotropic degree resulted in anisotropic structures (0.1% TFC and 0.3% TFC) and an isotropic structure (0.5% TFC). In the mechanical properties, it was evidenced greater resistance for the 0.3% TFC formulation. The addition of TPC percentages did not result in a significant difference (p > 0.05) in swelling capacity and disintegration rate. The results confirmed that TPC were able to modulate the morphological, morphometric, and mechanical properties of scaffolds. Thus, this study describes a potential new material to improve the regeneration of major tracheal structures after surgical tumor removal.
Subject(s)
Fibroins , Neoplasms , Psidium , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Fibroins/chemistry , Collagen/chemistry , Porosity , Spectroscopy, Fourier Transform InfraredABSTRACT
Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (-)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.
ABSTRACT
This work describes a new hair dyeing methodology using a chemical reaction between geniposide, an iridoid glycoside extracted from the fruit of Genipa americana (geniposide extract, GE) and the amine group of hair keratin. The influence of reaction conditions (pH, temperature, and extract concentration) on the staining of hair fibers, color development, fiber morphology, and mechanical hair properties of black and white human hair samples, was evaluated before and after GE dyeing treatment. Eye contact safety of GE was also studied using HET-CAM. The treatment of white hair fibers using GE at 20â mg mL-1 , temperature of 80 °C and pHâ 5.5 presented the greatest color change (ΔE=54.0). The higher pH influence was observed at pHâ 10.0 on white hair tresses (ΔE=6.8), using an GE concentration of 20â mg mL-1 and room temperature (25 °C). Treated samples showed marked changes on mechanical and morphological properties. The HET-CAM did not show any change, thus demonstrating that using GE is safe. In conclusion, the temperature and concentration of the extract were the variables that mostly influenced the color and hair damage. A new approach for hair dyeing was established where iridoids may potentially be useful as a natural hair dyeing.
ABSTRACT
The high levels of antibiotic resistance registered worldwide have become a serious health problem, threatening the currently available treatments for a series of infectious diseases. With antibiotics becoming less and less effective, it is becoming increasingly difficult and, in some cases, impossible to treat patients with even common infectious diseases, such as pneumonia. The inability to meet the ever-increasing demand to control microbial infection requires both the search for new antimicrobials and improved site-specific delivery. On the one hand, bacterial secondary metabolites are known for their diverse structure and antimicrobial potential and have been in use for a very long time in diverse sectors. A good deal of research is produced annually describing new molecules of bacterial origin with antimicrobial properties and varied applications. However, very few of these new molecules reach the clinical phase and even fewer are launched in the market for use. In this review article, we bring together information on these molecules with potential for application, in particular, for human and veterinary medicine, and the potential added value of the use of liposomes as delivery systems for site-specific delivery of these drugs with the synergistic effect to overcome the risk of antibiotic resistance.
ABSTRACT
Gelatin-based photopolymerizable methacrylate hydrogel (GelMA) is a promising biomaterial for in situ drug delivery, while aqueous extract of Punica granatum (AEPG) peel fruit rich in gallic acid and ellagic acid is used to improve wound healing. The aim of this study was to develop and analyze the healing properties of GelMA containing AEPG, gallic acid, or ellagic acid in a rodent model. GelMA hydrogels containing 5% AEPG (GelMA-PG), 1.6% gallic acid (GelMA-GA), or 2.1% ellagic acid (GelMA-EA) were produced and their mechanical properties, enzymatic degradation, and thermogravimetric profile determined. Wound closure rates, healing histological grading, and immunohistochemical counts of myofibroblasts were assessed over time. The swelling of hydrogels varied between 50 and 90%, and GelMA exhibited a higher swelling than the other groups. The GPG samples showed higher compression and Young's moduli than GelMA, GGA, and GAE. All samples degraded around 95% in 48 h. GPG and GGA significantly accelerated wound closure, improved collagenization, increased histological grading, and hastened myofibroblast differentiation in comparison to the control, GelMA, and GEA. GelMA containing AEPG (GPG) improved wound healing, and although gallic acid is the major responsible for such biological activity, a potential synergic effect played by other polyphenols present in the extract is evident.
Subject(s)
Gelatin , Hydrogels , Hydrogels/chemistry , Gelatin/chemistry , Ellagic Acid/pharmacology , Wound Healing , Gallic Acid , Methacrylates/chemistryABSTRACT
Metabolomics has proven to be an important omics approach to understand the molecular pathways underlying the tumour phenotype and to identify new clinically useful markers. The literature on cancer has illustrated the potential of this approach as a diagnostic and prognostic tool. The present study aimed to analyse the plasma metabolic profile of patients with oral squamous cell carcinoma (OSCC) and controls and to compare patients with metastatic and primary tumours at different stages and subsites using nuclear magnetic resonance and mass spectrometry. To our knowledge, this is the only report that compared patients at different stages and subsites and replicates collected in diverse institutions at different times using these methodologies. Our results showed a plasma metabolic OSCC profile suggestive of abnormal ketogenesis, lipogenesis and energy metabolism, which is already present in early phases but is more evident in advanced stages of the disease. Reduced levels of several metabolites were also associated with an unfavorable prognosis. The observed metabolomic alterations may contribute to inflammation, immune response inhibition and tumour growth, and may be explained by four nonexclusive views-differential synthesis, uptake, release, and degradation of metabolites. The interpretation that assimilates these views is the cross talk between neoplastic and normal cells in the tumour microenvironment or in more distant anatomical sites, connected by biofluids, signalling molecules and vesicles. Additional population samples to evaluate the details of these molecular processes may lead to the discovery of new biomarkers and novel strategies for OSCC prevention and treatment.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck , Biomarkers, Tumor/metabolism , Metabolomics/methods , Magnetic Resonance Spectroscopy , Tumor MicroenvironmentABSTRACT
Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy.
ABSTRACT
AIMS: The combination of daptomycin and ceftaroline used as salvage therapy is associated with higher survival and decreased clinical failure in complicated methicillin-resistant Staphylococcus aureus (MRSA) infections that are resistant to standard MRSA treatment. This study aimed to evaluate dosing regimens for coadministration of daptomycin and ceftaroline in special populations including paediatrics, renally impaired (RI), obese and geriatrics that generate sufficient coverage against daptomycin-resistant MRSA. METHODS: Physiologically based pharmacokinetic models were developed from pharmacokinetic studies of healthy adults, geriatric, paediatric, obese and RI patients. The predicted profiles were used to evaluate joint probability of target attainment (PTA), as well as tissue-to-plasma ratios. RESULTS: The adult dosing regimens of 6 mg/kg every (q)24h or q48h daptomycin and 300-600 mg q12h ceftaroline fosamil by RI categories achieved ≥90% joint PTA when the minimum inhibitory concentrations in the combination are at or below 1 and 4 µg/mL against MRSA. In paediatrics, wherein there is no recommended daptomycin dosing regimen for S. aureus bacteraemia, ≥90% joint PTA is achieved when the minimum inhibitory concentrations in the combination are up to 0.5 and 2 µg/mL for standard paediatric dosing regimens of 7 mg/kg q24h daptomycin and 12 mg/kg q8h ceftaroline fosamil. Model predicted tissue-to-plasma ratios of 0.3 and 0.7 in the skin and lung, respectively, for ceftaroline and 0.8 in the skin for daptomycin. CONCLUSION: Our work illustrates how physiologically based pharmacokinetic modelling can inform appropriate dosing of adult and paediatric patients and thereby enable prediction of target attainment in the patients during multitherapies.
Subject(s)
Bacteremia , Daptomycin , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Adult , Humans , Child , Aged , Daptomycin/pharmacokinetics , Anti-Bacterial Agents , Bacteremia/drug therapy , Staphylococcus aureus , Staphylococcal Infections/drug therapy , Cephalosporins/pharmacokinetics , Cephalosporins/therapeutic use , Microbial Sensitivity Tests , CeftarolineABSTRACT
HPV infection is one of the most important risk factors for head and neck squamous cell carcinoma among younger patients. YRNAs are short non-coding RNAs involved in DNA replication. YRNAs have been found to be dysregulated in many cancers, including head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the role of YRNAs in HPV-positive HNSCC using publicly available gene expression datasets from HNSCC tissue, where expression patterns of YRNAs in HPV(+) and HPV(-) HNSCC samples significantly differed. Additionally, HNSCC cell lines were treated with YRNA1-overexpressing plasmid and RNA derived from these cell lines was used to perform a NGS analysis. Additionally, a deconvolution analysis was performed to determine YRNA1's impact on immune cells. YRNA expression levels varied according to cancer pathological and clinical stages, and correlated with more aggressive subtypes. YRNAs were mostly associated with more advanced cancer stages in the HPV(+) group, and YRNA3 and YRNA1 expression levels were found to be correlated with more advanced clinical stages despite HPV infection status, showing that they may function as potential biomarkers of more advanced stages of the disease. YRNA5 was associated with less-advanced cancer stages in the HPV(-) group. Overall survival and progression-free survival analyses showed opposite results between the HPV groups. The expression of YRNAs, especially YRNA1, correlated with a vast number of proteins and cellular processes associated with viral infections and immunologic responses to viruses. HNSCC-derived cell lines overexpressing YRNA1 were then used to determine the correlation of YRNA1 and the expression of genes associated with HPV infections. Taken together, our results highlight the potential of YRNAs as possible HNSCC biomarkers and new molecular targets.
ABSTRACT
Traditional medicine uses resin oils extracted from plants of the genus Copaifera for several purposes. Resin oils are being studied to understand and profile their pharmacological properties. The aim of this work was to prepare and to characterize conventional and pegylated liposomes incorporating resin oils or the hexanic extract obtained from Copaifera sabulicola (copaiba) leaves. The cytotoxic effect of these products was also investigated. Conventional and stealth liposomes with copaiba extract showed similar average diameters (around 126 nm), encapsulation efficiencies greater than 75% and were stable for 90 days. A cytotoxicity test was performed on murine glioma cells and the developed liposomes presented antiproliferative action against these cancer cells at the average concentration of 30 µg/mL. Phytochemicals encapsulated in PEGylated liposomes induced greater reduction in the viability of tumor cells. In addition, bioassay-s measured the cytotoxicity of copaiba resin oil (Copaifera sabulicola) in liposomes (conventional and PEGylated), which was also checked against pheochromocytoma PC12 cells. Its safety was verified in normal rat astrocytes. The results indicate that liposomes encapsulating copaiba oil showed cytotoxic activity against the studied tumor strains in a dose-dependent fashion, demonstrating their potential applications as a chemotherapeutic bioactive formulation.
ABSTRACT
Chitosan films are commonly used for wound dressing, provided that this polymer has healing, mucoadhesiveness and antimicrobial properties. These properties can be further reinforced by the combination of chitosan with polysaccharides and glycoproteins present in aloe vera, together with copaiba oleoresin's pharmacological activity attributed to sesquiterpenes. In this work, we developed chitosan films containing either aloe vera, copaiba oil or both, by casting technique, and evaluated their microbial permeation, antimicrobial activity, cytotoxicity, and in vivo healing potential in female adult rats. None of the developed chitosan films promoted microbial permeation, while the cytotoxicity in Balb/c 3 T3 clone A31 cell line revealed no toxicity of films produced with 2 % of chitosan and up to 1 % of aloe vera and copaiba oleoresin. Films obtained with either 0.5 % chitosan or 0.5 % copaiba oleoresin induced cell proliferation which anticipate their potential for closure of wound and for the healing process. The in vivo results confirmed that tested films (0.5 % copaiba-loaded chitosan film and 0.5 % aloe vera-loaded chitosan film) were superior to a commercial dressing film. For all tested groups, a fully formed epithelium was seen, while neoformation of vessels seemed to be greater in formulations-treated groups than those treated with the control. Our work confirms the added value of combining chitosan with aloe vera and copaiba oil in the healing process of wounds.
Subject(s)
Aloe , Anti-Infective Agents , Chitosan , Female , Rats , Animals , Anti-Infective Agents/pharmacology , BandagesABSTRACT
The extract obtained from Mikania glomerata leaves rich in ent-kaurenoic acid (ERKA) shows cytotoxic activity in vitro, but its hydrophobic nature and thermosensitivity are issues to be solved prior to in vivo antitumor studies. The purpose of this study was to investigate the antitumor activity of inclusion complexes formed between ERKA and ß-cyclodextrin (ERKA:ß-CD) in rodents. ERKA:ß-CD complexes obtained by malaxation (MX) and co-evaporation (CE) methods were firstly characterized regarding their physical properties, encapsulation efficiency, and cytotoxicity againts L929 cells. The antitumor activity study was then performed in mice with sarcoma 180 treated with saline, 5-fluouracil (5FU) and ERKA:ß-CD at 30, 100 and 300 µg/kg. The weight, volume, percentage of inhibition growth, gross and pathological features and positivity for TUNEL, ki67, NFκB and NRF2 in the tumors were assessed. Serum lactate-dehydrogenase activity (LDH), white blood cells count (WBC) and both gross and pathological features of the liver, kidneys and spleen were also evaluated. The formation of the inclusion complexes was confirmed by thermal analysis and FTIR, and they were non-toxic for L929 cells. The MX provided a better complexation efficiency. ERKA:ß-CD300 promoted significant tumor growth inhibition, and attenuated the tumor mitotic activity and necrosis content, comparable to 5-fluorouracil. ERKA:ß-CD300 also increased TUNEL-detected cell death, reduced Ki67 and NF-kB immunoexpression, and partially inhibited the serum LDH activity. No side effect was observed in ERKA:ß-CD300-treated animals. The ERKA:ß-CD inclusion complexes at 300 µg/kg displays antitumour activity in mice with low systemic toxicity, likely due to inhibition on the NF-kB signaling pathway and LDH activity.