Novel vesicular bilosomal delivery systems for dermal/transdermal applications.

The application of therapeutically active molecules through the dermal/transdermal route into the skin has evolved as an attractive formulation strategy in comparison to oral delivery systems for the treatment of various disease conditions. However, the delivery of drugs across the skin is limited due to poor permeability. Dermal/transdermal delivery is associated with ease of accessibility, enhanced safety, better patient compliance, and reduced variability in plasma drug concentrations. It has the ability to bypass the first-pass metabolism, which ultimately results in steady and sustained drug levels in the systemic circulation. Vesicular drug delivery systems, including bilosomes, have gained significant interest due to their colloidal nature, improved drug solubility, absorption, and bioavailability with prolonged circulation time for a large number of new drug molecules. Bilosomes are novel lipid vesicular nanocarriers comprising bile salts, such as deoxycholic acid, sodium cholate, deoxycholate, taurocholate, glycocholate or sorbitan tristearate. These bilosomes are associated with high flexibility, deformability, and elasticity attributed to their bile acid component. These carriers are advantageous in terms of improved skin permeation, increased dermal and epidermal drug concentration, and enhanced local action with reduced systemic absorption of the drug, resulting in reduced side effects. The present article provides a comprehensive overview of the biopharmaceutical aspects of dermal/transdermal bilosome delivery systems, their composition, formulation techniques, characterization methods, and applications.

Application of Herbs and Dietary Supplements in ADHD Management.

Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder, which is characterised by a distinct clinical pattern of inattention, hyperactivity as well as impulsivity, which in turn interferes with the day-to-day activities of the affected individual. Although conventional allopathic medications have been found to provide symptomatic relief, they are accompanied by a plethora of side effects that overshadow and outweigh the potential therapeutic benefits. Hence, various alternative approaches in the management of Attention Deficit Hyperactivity Disorder (ADHD) are actively being investigated. Over the past few decades, numerous studies have been initiated and have delved into potential alternative strategies in the treatment and management of ADHD. The primary focus of this article is to discuss the etiology, pathophysiology coupled with a financial background as well as alternative strategies in the treatment and management of ADHD. A review of the literature on the clinical trialson alternative treatment approaches for ADHD showed that, plants and dietary supplements have beneficial effects on ADHD management. But in-depth studies still need to be conducted because the trials reported till now have a smaller sample size and need to be scaled up to get a broader understanding and knowledge of the potential impact of alternative forms of natural treatment on the patient population with ADHD. Also, the manufacturer of the alternative formulations needs to develop effective protocols and processes for the safe, effective, and robust manufacturing of such natural remedies, which fall in line with the expectation of the FDA to gain regulatory clearance for its manufacturing and sale, which can lead to better therapeutic outcomes in patients.

Antimicrobial Nanomaterials for Food Packaging.

Food packaging plays a key role in offering safe and quality food products to consumers by providing protection and extending shelf life. Food packaging is a multifaceted field based on food science and engineering, microbiology, and chemistry, all of which have contributed significantly to maintaining physicochemical attributes such as color, flavor, moisture content, and texture of foods and their raw materials, in addition to ensuring freedom from oxidation and microbial deterioration. Antimicrobial food packaging systems, in addition to their function as conventional food packaging, are designed to arrest microbial growth on food surfaces, thereby enhancing food stability and quality. Nanomaterials with unique physiochemical and antibacterial properties are widely explored in food packaging as preservatives and antimicrobials, to extend the shelf life of packed food products. Various nanomaterials that are used in food packaging include nanocomposites composing nanoparticles such as silver, copper, gold, titanium dioxide, magnesium oxide, zinc oxide, mesoporous silica and graphene-based inorganic nanoparticles; gelatin; alginate; cellulose; chitosan-based polymeric nanoparticles; lipid nanoparticles; nanoemulsion; nanoliposomes; nanosponges; and nanofibers. Antimicrobial nanomaterial-based packaging systems are fabricated to exhibit greater efficiency against microbial contaminants. Recently, smart food packaging systems indicating the presence of spoilage and pathogenic microorganisms have been investigated by various research groups. The present review summarizes recent updates on various nanomaterials used in the field of food packaging technology, with potential applications as antimicrobial, antioxidant equipped with technology conferring smart functions and mechanisms in food packaging.

Genus Zanthoxylum as Sources of Drugs for Treatment of Tropical Parasitic Diseases.

The tropical parasitic infections account for more than 2 billion infections and cause substantial morbidity and mortality, and account for several million deaths every year. Majorly parasitic infections in humans and animals are caused by protozoa and helminths. Chronic infections in the host can cause retardation, impairment of cognitive skills, development in young children and weaken the immune system. The burden is felt to a greater extent in developing countries due to poverty, inaccessibility to medicines and resistance observed to drugs. Thus, human health continues to be severely harmed by parasitic infections. Medicinal plants have received much attention as alternative sources of drugs. Zanthoxylum genus has been used ethnobotanically as an antiparasitic agent and the phytoconstituents in Zanthoxylum, show a wide variety of chemical substances with proven pharmacological actions such as alkaloids (isoquinolines and quinolines responsible for antitumor activity, antimalarial, antioxidant and antimicrobial actions), lignans, coumarins (antibacterial, antitumour, vasodilatory and anticoagulant activities), alkamide (strong insecticidal properties, anthelminthic, antitussive and analgesic anti antimalarial property). Therefore, this article is an attempt to review the existing literature that emphasizes on potential of genus Zanthoxylum as a source of lead compounds for the treatment of parasitic diseases.

Complexation of phytochemicals with cyclodextrins and their derivatives- an update.

Bioactive phytochemicals from natural source have gained tremendous interest over several decades due to their wide and diverse therapeutic activities playing key role as functional food supplements, pharmaceutical and nutraceutical products. Nevertheless, their application as therapeutically active moieties and formulation into novel drug delivery systems are hindered due to major drawbacks such as poor solubility, bioavailability and dissolution rate and instability contributing to reduction in bioactivity. These drawbacks can be effectively overcome by their complexation with different cyclodextrins. Present article discusses complexation of phytochemicals varying from flavonoids, phenolics, triterpenes, and tropolone with different natural and synthetic cyclodextrins. Moreover, the article summarizes complexation methods, complexation efficiency, stability, stability constants and enhancement in rate and extent of dissolution, bioavailability, solubility, in vivo and in vitro activities of reported complexed phytochemicals. Additionally, the article presents update of published patent details comprising of complexed phytochemicals of therapeutic significance. Thus, phytochemical cyclodextrin complexes have tremendous potential for transformation into drug delivery systems as substantiated by significant outcome of research findings.

Nanoparticles-Attractive Carriers of Antimicrobial Essential Oils.

Microbial pathogens are the most prevalent cause of chronic infections and fatalities around the world. Antimicrobial agents including antibiotics have been frequently utilized in the treatment of infections due to their exceptional outcomes. However, their widespread use has resulted in the emergence of multidrug-resistant strains of bacteria, fungi, viruses, and parasites. Furthermore, due to inherent resistance to antimicrobial drugs and the host defence system, the advent of new infectious diseases, chronic infections, and the occurrence of biofilms pose a tougher challenge to the current treatment line. Essential oils (EOs) and their biologically and structurally diverse constituents provide a distinctive, inexhaustible, and novel source of antibacterial, antiviral, antifungal, and antiparasitic agents. However, due to their volatile nature, chemical susceptibility, and poor solubility, their development as antimicrobials is limited. Nanoparticles composed of biodegradable polymeric and inorganic materials have been studied extensively to overcome these limitations. Nanoparticles are being investigated as nanocarriers for antimicrobial delivery, antimicrobial coatings for food products, implantable devices, and medicinal materials in dressings and packaging materials due to their intrinsic capacity to overcome microbial resistance. Essential oil-loaded nanoparticles may offer the potential benefits of synergism in antimicrobial activity, high loading capacity, increased solubility, decreased volatility, chemical stability, and enhancement of the bioavailability and shelf life of EOs and their constituents. This review focuses on the potentiation of the antimicrobial activity of essential oils and their constituents in nanoparticulate delivery systems for a wide range of applications, such as food preservation, packaging, and alternative treatments for infectious diseases.

An insight into cytotoxic activity of flavonoids and sesquiterpenoids from selected plants of Asteraceae species.

Cancer continues to be a disease that is difficult to cure and the current therapeutic regimen is associated with severe side effects and the issue of emerging drug resistance. According to the World Health Organization fact sheet 2017, cancer is the second major cause of morbidity and death and a 70% rise in new cases is expected over the next 20 years. The quest for new anticancer chemical entities is a thrust area identified by many government agencies and industry research and development groups. Nature-derived entities have played a very important role in therapeutics especially cancer Asteraceae is a large family consisting of around 1700 genera and more than 24,000 species. Several genera belonging to this family have ethnopharmacological uses such as cytotoxicity, antidiabetic, hepatoprotective and antioxidant. This review highlights the cytotoxic potential of structurally novel flavonoids and sesquiterpenes isolated from some selected species of Asteraceae plants native to Asia, Europe, parts of Africa and America. The existing literature suggests that sesquiterpenes and flavonoids from various species of Asteraceae represent a viable class of secondary metabolites with strong cytotoxic potential. These have demonstrated potent activity in cell cycle arrest, inhibition of neoangiogenesis and induction of apoptosis. The sesquiterpenoids exhibiting potent cytotoxic activity were found to contain an α- methylene-butyrolactone conjugated with an exomethylene group and the flavonoids obtained from various plant species of Blumea suggest that a dihydroxy ring system present in structure is essential for activity. Most of the published literature contains in vitro data of extracts/secondary metabolites with very few in vivo studies. Additionally, there is dearth of knowledge on mechanisms of cytotoxic activity and molecular targets impacted by the active secondary metabolites. This review hopes to fuel interest in researchers to take up detailed investigations on these scaffolds that could contribute significantly as potential leads in anticancer drug development.

Cytotoxic Activity and Initiation of Apoptosis via Intrinsic Pathway in Jurkat Cells by Leaf Extract of Zanthoxylum rhetsa DC.

BACKGROUND: Newer drugs are in demand for leukemia treatment that specifically targets tumor cells without affecting normal cells. Potent cytotoxic activities have been reported from various parts of Zanthoxylum rhetsa. Thus, the present study was conducted to evaluate antileukemic potential of leaf extract of Z. rhetsa along with probable mechanism of cytotoxicity. Materials and Methods: The antiproliferative activity of the extract on leukemic cell lines was evaluated using sulforhodamine B assay. The changes in cell death profile, cell cycle, and expression levels of pro-apoptotic markers (p53, Bax, cytochrome C, caspase 3, and MMP) and antiapoptic marker (Bcl2) on Jurkat cell lines were studied using flow cytometer. Comparison of oxidative stress induced by extract on Jurkat cells and normal mouse fibroblast cells was done. DNA fragmentation was studied using gel electrophoresis. Results: The leaf extract showed concentration-dependent cytotoxicity against Jurkat cell lines majorly via apoptotic mechanism. It arrested cells at G0/G1 and S phase of cell cycle. Apoptosis was associated with increase in the expression of pro-apoptotic markers and decrease of anti-apoptotic markers. The treatment with extract selectively increased the oxidative stress in Jurkat cells and showed DNA fragmentation. Conclusion: The methanol extract of leaves of Z. rhetsa show selective cytotoxic activity on Jurkat cell lines and induced apoptosis via intrinsic pathway.

Development and Evaluation of a Novel Delivery System Containing Phytophospholipid Complex for Skin Aging.

Citrus auranticum and Glycyrrhiza glabra are rich in anti-oxidant polyphenols helpful in prevention of skin aging. Polyphenols have high polarity and lower skin penetration resulting in lower cutaneous delivery. The present work is attempted to develop a novel polyherbal phospholipid complex cream to improve cutaneous delivery of polyphenols for sustained anti-oxidant action. Phytochemical and in vitro anti-oxidant evaluation was done on methanolic extracts of orange peel and liquorice powder. Total phenolic content, total flavonoid content, and anti-oxidant assays were done on different ratios of orange peel and liquorice extract. Ratio 1:2 gave highest total phenolic content (TPC) (530.00 ± 1.56 mg gallic acid equivalent (GAE) g(-1) extract), total flavonoid content (TFC) (246.25 ± 1.03 mg rutin equivalent (RUE) g(-1) extract), 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity (87.99 ± 0.64%), and H2O2 scavenging activity (72.47 ± 0.86%) and hence was used for formulation. Solvent evaporation method using methanol with 1:1 extract to phospholipid ratio was found to have entrapment efficiency of 93.22 ± 0.26%. Evaluation parameters like scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FT-IR), and differential scanning calorimetry (DSC) confirmed formation of complex. The complex was formulated as oil-in-water cream and evaluated for various parameters. The optimized cream containing 1% complex was non-irritant and was found to be stable for 3-month period under conditions of stability study. Ex vivo diffusion studies showed that extract phospholipid complex cream had better retention of polyphenols in the skin when compared to conventional extract cream giving prolonged and stronger topical action. The cream had an anti-elastase activity of 28.02 ± 0.95% at concentration of 3000 µg ml(-1) (w/v). Thus, the developed safe and stable polyherbal phytophospholipid complex cream exhibited good potential as anti-aging cosmeceutical.