Borneol is a bicyclic monoterpenoid alcohol commonly used in traditional Chinese and Indian medicine. It is extracted from the essential oil of various medicinal plants. It has antibacterial, ...analgesic, and anti-inflammatory action proven in studies that used oral and intraperitoneal applications of this monoterpene in mice. The current study was designed to develop a topical gel formulation containing the monoterpene borneol using carbopol as gel base and to evaluate its stability. The prepared formulation was subjected to physical characterization and physical-chemistry assessment. The gel was prepared from carbopol and 5% of borneol. The prepared gel was subjected to pharmacotechnical tests such as its pH, viscosity, conductivity, spreadability, centrifugation, and accelerated stability with freezing-thaw cycle. The borneol was successfully incorporated into the carbopol formulation. Borneol gel (BG5) showed good stability after eight months of its development and after 12 days in the freeze-thaw cycle, not showing statistical difference in pH value, conductivity, and viscosity before and after test. Furthermore, the formulation showed a good spreadability. Therefore, it was concluded that the formulation could be very promising alternative for the topical or transdermal treatment of skin diseases.
Abstract
Burn injuries are observed throughout a wide range of ages, with over 1.1 million Americans suffering burns yearly, and half of these require hospitalization. Epigenetic modifications are ...fast-acting mechanisms that allow the human body to respond and adapt to environmental changes, including burn injuries. There is a lack of understanding of the epigenetic role during burn-induced tissue repair. Here, we characterize the histone modifications that follow burn injury, aiming at future pharmacological intervention using drugs capable of targeting epigenetic events. A clinically relevant porcine burn model was used to recapitulate the skin healing process after the burn. Isolated skin tissues at different time points were used to detect the acetylation levels of histones H3K27, H4K5, H4K8, and H4K12 as significant players of gene transcription using MetaXpress High-Content Imaging Analysis. We observed that the acetylation of histones is dynamically adjusted throughout healing, and its modifications are uniquely expressed according to the anatomical location and time of healing. We also observed that histone H4K5 is the most widely expressed during healing, followed by histone H3K27. We observed that histones expressed in intact skin tissue adjacent to the burn site could sense the burn injury by changing its histone acetylation pattern compared to control skin from uninjured and distant skin. Using a clinically relevant animal model, we have generated a comprehensive landscape of epigenetic modifications during burn healing. Our data will help us identify novel epi-drugs capable of manipulating histone modifications during healing to accelerate the healing process.
β-Lapachone is an ortho-naphthoquinone originally isolated from the heartwood of Handroanthus impetiginosus and can be obtained through synthesis from lapachol, naphthoquinones, and other aromatic ...compounds. β-Lapachone is well known to inhibit topoisomerase I and to induce NAD(P)H: quinone oxidoreductase 1. Currently, phase II clinical trials are being conducted for the treatment of pancreatic cancer. In view of ever-increasing scientific interest in this naphthoquinone, herein, the authors present a review of the synthesis, physicochemical properties, biological activities, and toxicity of β-lapachone. This natural compound has shown activity against several types of malignant tumors, such as lung and pancreatic cancers and melanoma. Furthermore, this ortho-naphthoquinone has antifungal and antibacterial activities, underscoring its action against resistant microorganisms and providing anti-inflammatory, antiobesity, antioxidant, neuroprotective, nephroprotective, and wound-healing properties. β-Lapachone presents low toxicity, with no signs of toxicity against alveolar macrophages, dermal fibroblast cells, hepatocytes, or kidney cells.
Display omitted
•The formation of ROS is the primary mechanism of β-lapachone against cancer cells.•The β-lapachone has shown antiviral, antiparasitic and antimicrobial effects.•Anti-inflammatory activities of β-lapachone may be due to synergistic mechanisms.•β-lapachone has potential therapeutic effects on obesity by the fat-browning effect.•β-Lapachone is able to suppress metastasis in vivo by several mechanisms.
Chagas disease (CD), caused by the flagellate protozoan Trypanosoma cruzi, is one of the major public health problems in developing countries. Benznidazole (BNZ) is the only drug available for CD ...treatment in most countries, however, it presents high toxicity and low bioavailability. To address these problems this study used Zeolitic Imidazolate Framework-8 (ZIF-8), which has garnered considerable attention due to its potential applications, enabling the controlled delivery of drugs. The present work developed and characterized a BNZ@ZIF-8 system, and the modulation of BNZ release from the ZIF-8 framework was evaluated through the in vitro dialysis release method under sink conditions at different pH values. Moreover, the in vitro evaluation of cell viability and cytotoxicity by MTT assay were also performed. The dissolution studies corroborated that a pH sensitive Drug Delivery System capable of vectorizing the release of BNZ was developed, may leading to the improvement in the bioavailability of BNZ. The MTT assay showed that no statistically significant toxic effects occurred in the developed system, nor significant effects on cell viability.
► Olanzapine, a high cost drug, is the most important antipsychotic drug on the market. ► Olanzapine has low aqueous solubility, affecting its dissolution and absorption. ► Methyl-β-cyclodextrin was ...the most effective alternative to olanzapine drug delivery. ► The product developed has higher stability and dissolution rate than the drug alone.
Olanzapine (OLP), the most important atypical antipsychotic drug of the new generation, a high cost drug, has low aqueous solubility, affecting its dissolution and absorption. Its complexation with modified cyclodextrins (CDs) is designed to achieve novel vectorization systems with higher solubility, consequently higher bioavailability. From the CD selection, among β-CD, methyl-β-CD (MβCD) and hydroxypropyl-β-CD, it was obtained a phase solubility diagram suggesting a 1:1 (mol:mol) OLP–CD stoichiometry and complexation constants of 966.9, 149.4 and 91.1L/mol, respectively. The MβCD was selected for the inclusion complexes (IC) attainment, a physical mixture (PM) and a rotatory evaporator product (ROE). The analysis showed differences in the structure, morphology and performance of OLP, MβCD, PM and ROE, revealing the occurrence of interactions between drug and CD. The ROE presented the higher dissolution efficiency and stability. The results suggest that the IC was formation, being a technological resource efficient and profitable for drug delivery.
Schistosomiasis: Drugs used and treatment strategies Siqueira, Lidiany da Paixão; Fontes, Danilo Augusto Ferreira; Aguilera, Cindy Siqueira Britto ...
Acta tropica,
December 2017, 2017-Dec, 2017-12-00, 20171201, Letnik:
176
Journal Article
Recenzirano
•Public politics must be more effective for the endemic control of schistosomiasis.•The number of drugs used to treat NTDs is very small, because that the investment in R&D for such diseases is ...inadequate.•Currently, some pharmaceutical companies have R&D units with major university centers focusing on the neglected diseases.
Neglected tropical diseases (NTDs) affect millions of people in different geographic regions, especially the poorest and most vulnerable. Currently NTDs are prevalent in 149 countries, seventeen of these neglected tropical parasitic diseases are classified as endemic. One of the most important of these diseases is schistosomiasis, also known as bilharzia, a disease caused by the genus Schistosoma. It presents several species, such as Schistosoma haematobium, Schistosoma japonicum and Schistosoma mansoni, the latter being responsible for parasitosis in Brazil. Contamination occurs through exposure to contaminated water in the endemic region. This parasitosis is characterized by being initially asymptomatic, but it is able to evolve into more severe clinical forms, potentially causing death. Globally, more than 200 million people are infected with one of three Schistosome species, including an estimated 40 million women of reproductive age. In Brazil, about 12 million children require preventive chemotherapy with anthelmintic. However, according to the World Health Organization (WHO), only about 15% of the at-risk children receive regular treatment. The lack of investment by the pharmaceutical industry for the development and/or improvement of new pharmaceutical forms, mainly aimed at the pediatric public, is a great challenge. Currently, the main forms of treatment used for schistosomiasis are praziquantel (PZQ) and oxaminiquine (OXA). PZQ is the drug of choice because it presents as a high-spectrum anthelmintic, used in the treatment of all known species of schistosomiasis and some species of cestodes and trematodes. OXA, however, is not active against the three Schistosome species. This work presents a literature review regarding schistosomiasis. It addresses points such as available treatments, the role of the pharmaceutical industry against neglected diseases, and perspectives for treatment.
Pentavalent antimonials are the primary treatment for leishmaniasis due to their proven efficacy and cost-effectiveness. However, they present poor oral absorption, parenteral administration, and ...serious adverse effects due to prolonged use. Nanostructured Lipid Carriers (NLC) offer a promising solution, providing prolonged release, enhanced intestinal permeability, and oral bioavailability. This study aimed to address these issues by developing Nanostructured Lipid Carrier loaded with meglumine antimoniate (NLC-MA) for oral leishmaniasis treatment. We used design of experiments (DoE) for optimization. The chosen NLC-MA was characterized assessing size, polydispersity index (PdI), zeta potential (ZP), entrapment efficiency (EE), pH, and by analytical techniques such as DSC, FTIR, XRD, and TEM. Stability under simulated gastrointestinal conditions, in vitro release kinetics, cytotoxicity in RAW 264.7 macrophages, and leishmanicidal activity were assessed. NLC-MA presented 41.13 nm, PdI 0.227, ZP −27.9 mV, EE of 62.43%, and pH 5.23. Characterization techniques confirmed drug incorporation and nanoparticles with reduced crystallinity. TEM images showed spherical morphology. NLC remained stable in gastrointestinal pH and under refrigeration storage, while lyophilized formulations retained their initial properties. MA release from NLC followed the Peppas-Sahlin model, an anomalous transport mechanism. Importantly, MA showed no cytotoxicity in macrophages, but the NLCs exhibited cytotoxicity beyond 50 µg/mL. NLC-MA displayed improved efficacy against Leishmania infantum. Overall, these results highlight the potential of utilizing a lipid nanocarrier incorporating meglumine antimoniate as an innovative drug delivery platform for oral treatment against leishmaniasis.
Display omitted
•The design of experiments provided better lipid formulation for the nanoparticle.•Nanostructured Lipid Carrier containing meglumine antimoniate was developed.•Simulated gastric stability of the nanocarrier was observed.•The nanocarrier promoted in vitro release kinetics longer than 48 h.•In vitro leishmanicidal activity was better in the L. infantum specie.
Layered Double Hydroxides (LDH) have received great attention in the development of drug carrier systems. LDHs have become intelligent excipients of high technological potential for the ...pharmaceutical industry due to their ability to intercalate biomaterials in the interlayer region, adsorb substances on its vast surface area, have flexible structure, swelling properties, high chemical and thermal stability, modulate drug release, have high biocompatibility and be easily synthesized. This article, using typical examples, mainly addresses the systems formed between LDHs and antimicrobial, antineoplastic and anti-inflammatory agents, which constitute the main pharmacological classes of wide interest due to the problems encountered with low solubility, control in administration, stability in body fluids and toxicity, among others. Additionally, the article also reports on the recent development of ternary or quaternary (multicomponent systems) compounds based on LDH, bringing the advantages of targeted therapy, improving the aqueous stability of nanohybrids and the performance of these inorganic carriers.
Display omitted
Water resource variables are highly complex and vary both spatially and temporally. Understanding the variability and how it evolves has been an important scientific question in Ceará, Brazil. ...However, describing and determining the uncertainty and the variability in precipitation is still a challenge. Assessing the uncertainty around precipitation is key to develop robust and proactive planning. This study's main aim is to evaluate the underlying spatiotemporal variability of precipitation in the State of Ceará at different timescales by using standardized variability indices computed from different entropy measures. This methodology was applied to analyze 31 meteorological stations with daily time series from 1962 through 2006 while expanding the analysis to the remaining region using an interpolation method. The seasonal timescale analysis revealed that the dry season contributes more to the annual variability, and the change in intra-annual precipitation dynamics could vary with timescales. There were significant upward trends in entropy. Thus, for some stations, there was an increase in the uncertainty of rainfall. Also, there was an increase in variability amount and intensity throughout the decades at the monthly and seasonal timescales. Assessment of precipitation uncertainty within different timescales can benefit a broad community of scientists who are interested in arid-region and natural hazards.
Improved water resource management relies on accurate analyses of the past dynamics of hydrological variables. The presence of low-frequency structures in hydrologic time series is an important ...feature. It can modify the probability of extreme events occurring in different time scales, which makes the risk associated with extreme events dynamic, changing from one decade to another. This article proposes a methodology capable of dynamically detecting and predicting low-frequency streamflow (16–32 years), which presented significance in the wavelet power spectrum. The Standardized Runoff Index (SRI), the Pruned Exact Linear Time (PELT) algorithm, the breaks for additive seasonal and trend (BFAST) method, and the hidden Markov model (HMM) were used to identify the shifts in low frequency. The HMM was also used to forecast the low frequency. As part of the results, the regime shifts detected by the BFAST approach are not entirely consistent with results from the other methods. A common shift occurs in the mid-1980s and can be attributed to the construction of the reservoir. Climate variability modulates the streamflow low-frequency variability, and anthropogenic activities and climate change can modify this modulation. The identification of shifts reveals the impact of low frequency in the streamflow time series, showing that the low-frequency variability conditions the flows of a given year.
PDF
