Dual combination of resveratrol and pterostilbene aqueous core nanocapsules for integrated prostate cancer targeting.

Aim: Development and evaluation of aqueous core nanocapsules (ACNs) of BCS-II-class drug like resveratrol (RSV) and pterostilbene (PTE) for prostate cancer.Materials & methods: Identify synergistic effects of molar ratios of RSV and PTE against PC-3 cell. Selected ratio of drugs was added to ACNs by double-emulsification-method using Box-Behnken design. Further, assessed for physicochemical characterization, release kinetics, compatibility, in vitro cytotoxicity, in vivo pharmacokinetic and biodistribution studies.Results: Selected 1:1 ratio of RSV and PTE had greatest synergy potential have smaller particle-size (128.1 ± 3.21 nm), zeta-potential (-22.12 ± 0.2 mV), 0.53 PDI, improved encapsulation (87% for RSV, 72% for PTE), stable, no systemic toxicity, high biodistributed/accumulated in prostate cells.Conclusion: ACNs exhibited high t1/2 (12.42 ± 1.92 hs) and 8.20 ± 8.21 hs Mean Residence Time and lower clearance, proving the high effectiveness for prostate cancer.

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Nanoemulsions a Delivery System in the Making for Tumor Targeting Therapeutics: Evaluation and Characterization to Meet Clinical Challenges.

Cancer is a complex disease characterized by the uncontrolled and unregulated growth of cells followed by invasion and proliferation from the site of origin to other sites of the body. Conventional chemotherapy largely kills rapidly expanding and dividing cancer cells by impairing DNA synthesis and mitosis. It is associated with various types of adverse effects ranging from simple nausea and appetite loss to serious ones like bone marrow depression and compromised immunity etc., due to their non-selectivity and inability to differentiate. The ideal feature of a delivery system is delivering the drug to the target place to achieve the most therapeutic impact while having the least toxicity. With the advent of novel drug delivery systems, it has been easier to deliver the drug to the target site. Utilizing new techniques and technology makes it a feasible approach to target cancer cells. Nanoemulsions are isotropic mixtures of transparent or translucent oil globules dispersed in an aqueous phase that is kinetically stable and supported by an interfacial coating of surfactant and co-surfactant molecules with droplet sizes in the nanometre range. Nanoemulsions are the delivery system of choice in case of cancer because of certain key attributes, including biodegradability, biocompatibility, large surface area nonimmunogenicity, and release behavior control. At the same time, nanoemulsions have been engineered for various reasons, including enhanced biological half-life, target-specific binding ability, and imaging capability at different therapy levels by modifying the characteristics of nanoemulsions. This review focuses on current cancer treatment challenges and the role of nanoemulsions in treating cancer with their production methods, characterization methods, application, and quality attributes, which would help them make it to the clinics where cancer treatment is going on.

Comprehensive Review on Herbal Medicine: Emphasis on Current Therapy and Role of Phytoconstituents for Cancer Treatment.

INTRODUCTION: Cancer poses a significant public health challenge in both developed and developing nations, with a rising global incidence of patients facing the threat of death due to abnormal cell proliferation. AIM: Review explores the utilization of different parts of herbal medicinal plants and their active pharmaceutical constituents in the prevention and treatment of various types of cancer. METHODOLOGY: Various anticancer medicinal plants have been identified, demonstrating their therapeutic effects by inhibiting cancer-stimulating enzymes and hormones, activating DNA repair processes, boosting the synthesis of protective stimulants, reducing the formation of free radicals, and enhancing individual immunity. Data for this study were gathered from diverse online bibliographic and databases, including Google, Google Scholar, Mendeley, Springer Link, Research Gate, and PubMed. RESULT: Herbal drugs have a huge contribution to the inhibition of the progression of cancer.A large volume of clinical studies has reported the beneficial effects of herbal medicines on the survival, immune modulation, and quality of life (QOL) of cancer patients, when these herbal medicines are used in combination with conventional therapeutics. CONCLUSION: The latest medicines for the clinical purpose (Above 50 %) are derived from herbal products. Furthermore, combination of these herbs with nanotechnology shows promise in treating specific carcinomas.

Natural Polyphenols in Cancer Management: Promising Role, Mechanisms, and Chemistry.

BACKGROUND: Although cancers emerge rapidly and cancer cells divide aggressively, which affects our vital organ systems. Recently, cancer treatments are targeted immune systems mediating intrinsic cellular mechanisms. Natural efficacious polyphenols have been exhibited to help prevent most cancers and reverse the progression of cancers. METHODS: Many resources have been used to know the promising role of polyphenols in preventing and treating cancers. The electronic databases include Science Direct, Google, Google Scholar, PubMed, and Scopus. The search was limited to the English language only. RESULTS: Polyphenols have been reported as anti-metastatic agents that explore the promising role of these compounds in cancer prevention. Such agents act through many signaling pathways, including PI3K/Akt and TNF-induced signaling pathways. The chemical modifications of polyphenols and the structure-activity relationships (SARs) between polyphenols and anti-cancer activities have also been discussed. CONCLUSION: Many research papers were reported to explain the anti-cancer potential of Polyphenols, The SARs between polyphenols and anti-cancer activities, which correlate structures of polyphenols with significant chemotherapeutic action. The mechanism of anti-cancer potential is to be added for searching for new anti-cancer natural products.

Recent Advancement in Synthesis and Bioactivities of 1,3,4-Oxadiazole.

Derivatives of 1,3,4-oxadiazole are effective in the treatment and cure of a wide range of diseases in medical chemistry, while industrial development has shown that they can be utilised as corrosion inhibitors and light-emitting diodes. The researchers discovered several promising synthetic strategies that created 1,3,4-oxadiazoles in extraordinarily high yields while using environmentally friendly methods. These compounds can potentially be used in a wide range of lifechanging applications. Stable isomeric oxadiazole forms of pleconaril, raltegravir, butalamine, fasiplon, oxolamine, and several other drugs are among the numerous potent and effective pharmaceuticals that are now on the market. Fasiplon, butalamine, raltegravir, and pleconaril treat HIV/AIDS patients. This article has attempted to bring attention to the chemistry and pharmacology of oxadiazole and its derivatives. Oxadiazole derivatives have been used extensively as prospective therapeutic agents in clinical research, and this has become standard practice. The use of biological and in-silico models has enabled scientists to identify more synthetic analogues of cancer prevention, antifungal, and anti-HIV medications. This article provides recent information regarding procedures for synthesizing 1,3,4-oxadiazoles and their biological actions on the body.

Development, evaluation, pharmacokinetic and biodistribution estimation of resveratrol-loaded solid lipid nanoparticles for prostate cancer targeting.

BACKGROUND AND AIM: The study was to extend systemic circulation and biological half-life (t1/2) of trans-resveratrol (RSV) using solid lipid nanoparticles (RSV-SLN) to improve its anti-cancer potential. METHODS: RSV-SLN was prepared by solvent emulsification evaporation technique and proceeded for evaluation like particle size, PDI, zeta potential, in vitro release, in vitro cytotoxicity, cellular internalisation, haemolysis and erythrocyte membrane integrity, platelet aggregation and pharmacokinetic studies in rats. Moreover, cancer cells accumulation of RSV-SLN also needs to be evaluated for proving their targeting ability. RESULT: Prepared SLN showed 126.85 ± 12.09 nm particle size, -24.23 ± 3.27 mV Zeta potential and 74.67 ± 4.76%. release at 48 h and haemocompatible. The cellular internalisation image showed the SLN reach in a cytoplasm and nucleus of PC3 prostate cells. RSV-SLN exhibited high t1/2 (8.22 ± 1.36 h) and 7.19 ± 0.69 h MRT (Mean residence time) and lower clearance i.e. 286.42 ± 13.64 mL/min/kg. The bio-distribution of RSV-SLN was found to be extremely high in prostate cells and accumulate 7.56 times greater than that of RSV solution. CONCLUSION: The developed RSV-SLN can be applied as potential carrier for delivery of drug of chemotherapeutics at an extend systemic circulation and targeting efficiency at tumour site.

Caveolins: Expression of Regulating Systemic Physiological Functions in Various Predicaments.

Caveolins are membrane proteins which contains caveolae. They are present in the plasma membrane. Many researchers found that caveolae have been associated with expression of the caveolins in major physiological networks of mammalian cells. Subtypes of caveolin including caveolin-1 and caveolin-2 have been found in micro arteries of rat brain, while caveolin-3 has been found in astrocytes. Caveolin-1 and caveolae play important roles in Alzheimer's disease, cancer, ischemic preconditioning-mediated cardio-protection, postmenopausal alterations in women, and age-related neurodegeneration. Caveolin-1 may modify fatty acid transmembrane flux in adipocytes. The discovery of a link between ischemia preconditioning, cardio-protection, and endothelial nitric oxide synthase has supported cardiovascular research tremendously. Therefore, caveolins are effective in regulation of cellular, cardiovascular, brain, and immune processes. They ascertain new signalling pathways and link the functionalities of these pathways. This review paper focuses on contribution of caveolins in various conditions, caveolin expression at the molecular level and their physiological effects in many organ systems.

Ceiling effect of Postconditioning and Atrial Natriuretic Peptide in Cardioprotection against Ischemia Reperfusion Injury in Ovariectomized rat hearts

Abstract Ischemic postconditioning (IPTC) brings cardioprotection endogenously, Atrial natriuretic peptide (ANP) produces the same effect. It happens due to down expression of endothelial nitric oxide synthase (eNOS). Thus, experimental protocol associating IPTC has been formulated to find the role of ANP in the cardioprotection of heart in OVX rats. For this experiment, heart was isolated from OVX rat and held tightly on Langendorff's apparatus in a manner that ischemia of 30 min and reperfusion of 120 min were also given. Simultaneously, IPTC with four cycles of 5 min ischemia and 5 min reperfusion of each was applied. Parameters like size of myocardial infarct, levels of lactate dehydrogenase (LDH) and release of creatine kinase- MB (CK-MB) in coronary effluent were noted after each stage of experiment for ensuring the extent of myocardial injury. Some significant changes were also seen in the histopathology of cardiovascular tissues. The cardio-protection has been made by four cycles of IPTC. It was confirmed by decline in the size of myocardial infarct. It diminishes the release of LDH and CK-MB in heart of OVX rat. Thus, IPTC induces cardio-protection in the isolated heart from OVX rat. Perfusion of ANP associating with IPTC favors the cardioprotection which is further confirmed by rise in the NO release and heart rate. The level of myocardial damage changes using IPTC, IPTC+OVX, IPTC+OVX+ANP, IPTC+ OVX+ANP+L-NAME and other groups were observed significantly and were found to be less than those in I/R control group. Thus, it is recommended that ANP involving IPTC restores attenuated cardio-protection in OVX rat heart. Therefore, Post-conditioning is useful in various clinical aspects.

Invasomes for Enhanced Delivery through the Skin: Evaluation of Systems to Meet with Clinical Challenges.

BACKGROUND: Portage of therapeutic agents directly to the skin (cutaneous/dermal delivery) is the preferable approach in mitigating and curing a variety of skin manifestations, including itching, eczema, acne, psoriasis keratinization, and skin cancer. Dermal delivery reduces side effects associated with systemic therapy and allows maximum utilization of the available doses. Invasomes are the next generation of liposomes with greater flexibility, elasticity, and permeability through the skin than liposomes and ethosomes. OBJECTIVE: This review article highlights various aspects of invasomes, including the structure and composition of invasomes, methods of preparation of invasomes, the mechanism involved in better penetration through the skin, key parameters to be considered for effective permeation, therapeutic applications of invasomes as novel drug delivery systems, and future development and challenges. METHODS: The authors have reviewed various primary and secondary sources, including PUBMED, SCIENCE DIRECT, INFORMA, and patents.com, to collect information on various aspects of invasomes. RESULTS AND CONCLUSION: Invasomes are novel vesicular drug delivery systems that have been used for dermal delivery of drugs for various therapeutic applications. These novel carriers have great ability, and their properties can be highly modulated by varying their composition and concentration of terpenes. Based on all the research reports gathered, it is well proven that these systems have a much higher potential for delivering drugs for skin manifestations and could expand the opportunities for treating various dermatological issues, increasing day by day.

Angiotensin (1-7) facilitates cardioprotection of ischemic preconditioning on ischemia-reperfusion-challenged rat heart.

Ischemic preconditioning (IPC) is one of the most promising strategies used to protect the myocardium from ischemia-reperfusion injury. Ang (1-7) exhibits cardioprotective activity; however, its therapeutic potential on IPC-induced cardioprotection has not been reported in ischemia-reperfusion injury till date. Therefore, the first set of experiment was designed to evaluate the direct effect of Ang (1-7), in perfusion medium, on cardioprotective activity of IPC in rat heart challenged to ischemia-reperfusion injury. In addition, the acute and chronic effects of pretreated Ang (1-7) were investigated on cardioprotection of IPC in ischemia-reperfusion-challenged hearts in subsequent sets of experiments. The results showed that Ang (1-7) potentiated the IPC-induced increase in coronary flow and heart rate, decrease in lactate dehydrogenase and creatine kinase activity, ventricular fibrillation, and infarct size in ischemia-reperfusion-challenged animals in direct and chronic sets of experiments. Further, Ang (1-7) enhanced the IPC-induced attenuation in mitochondrial dysfunction, oxidative stress, and apoptosis in ischemia-reperfusion-challenged hearts in both sets of experiments. A-779, Mas receptor antagonist, abrogated potentiation effects of Ang (1-7) on IPC-induced cardioprotection in ischemia-reperfusion-challenged rats in the above set of experiments. These observations indicate that Ang (1-7)/Mas receptor activation could be a potential adjuvant to IPC during ischemia-reperfusion-induced cardiac injury.

Neural network-based evaluation of chronic non-thermal effects of modulated 2450 MHz microwave radiation on electroencephalogram.

The effects of chronic exposure (2 h daily for 21 days) of 1 kHz square wave-modulated 2450 MHz microwave radiation (non-thermal) on sleep-EEG, open field behavior, and thyroid hormones (T(3), T(4), and TSH) have been analyzed in an animal model. Results revealed significant changes in these pathophysiological parameters (p < 0.05 or better), except body temperature, grooming behavior, and TSH levels. The sleep-EEG power spectrum data for slow wave sleep (SWS), rapid eye movement (REM) sleep, and awake (AWA) states in two experimental groups of rats (microwave exposed and the control) were tested by an artificial neural network (ANN), containing 60 nodes in input layer, weighted from power spectrum data from 0 to 30 Hz, 18 nodes in hidden layer and an output node. The target output values for this network were determined with another five-layered neural network (with the structure of 6-14-1-14-6). The input and output of this network was assigned with the six confirmed pathophysiological changes. The most important feature for chronic exposure of 2450 MHz microwave exposure and for control subjects was extracted from the third layer single neuron and used as the target value for the three-layered ANN. The network was found effective in recognizing the EEG power spectra with an average of 71.93% for microwave exposure and 93.13% for control subjects, respectively. However, the lower percentage of pattern identification agreement in the microwave-exposed group in comparison to the control group suggest only mild effects of microwave exposure with this experimental setup.