Nanofiber devices for the targeted-delivery of therapeutically active plant and herbal ingredients

Herbal and plant based remedies have been used since times immemorial for treating illnesses or maladies of variant aetiology, whereas during the past two centuries, the pharmaceutical chemists have discovered many important modern drugs from natural botanicals and microbes. Generally, herbal and plant-derived products containing multiple compounds are administered orally for therapeutic purposes. Currently, targeted drug-delivery systems are being developed and investigated for the treatment of cardio-respiratory disorders, pain relief, wound healing, and life threatening diseases like cancers. A number of novel nanofiber membranes and devices are available for sustained release and to deliver steady supply of natural bioactive ingredients, herbal-based extracts, and a few have been approved by US-FDA and other drug regulatory agencies. The purpose of this mini review is to provide an update on the role of nanofiber devices used for the targeted-delivery of therapeutically active ingredients of plant and herbal origin as well as to underscore the potential for the delivery of cost-effective herbal ingredients and natural plant-based extracts for their biomedical applications in wound healing, inflammation-related diseases and cancer treatment. Biomed Rev 2015; 26: 37-42.Key words: targeted-delivery, natural botanicals, plant-derived ingredients, nanofibrous medical devices, biodegradable and biocompatible polymer

Celiac disease: Role of genetics and immunity and update on novel strategies for treatment

Celiac disease (CD) is one of the most common inflammatory diseases of the small intestine which causes abdominal pain, diarrhoea, malabsorption, weight loss, anorexia, and iron deficiency anaemia in humans. It is a human leukocyte antigen (HLA)-linked disorder that is triggered by the gluten and gliadin proteins from wheat and related cereals. The presence of other genetic factors such as HLA-DQ2 and HLA-DQ8 have also been identified for the generation of circulating autoantibodies to the enzyme transglutaminase (TG2). The TG2 enzyme deamidates the gluten peptides and increases their affinity for the HLA-DQ2 or HLA-DQ8, which in turn cause a more vigorous activation of CD4+ T-helper 1 (Th1) cells and trigger the immune response, and such immune cascade eventually leads to intestinal membrane damage and malabsorption. Generally, CD is managed by lifelong gluten-free diet. However, strict adherence to a gluten-free diet is difficult and is not always effective. Several pharmacological agents and alternative therapies for treating CD are currently under development and are in clinical trials, The purpose of this review is to highlight the complex involvement of genetics and immunity in CD and to focus on the novel strategies being used for developing adjunct and alternative therapies for the treatment of CD.Biomedical Reviews 2014; 25: 45-58

Lactose intolerance: genetics of lactase polymorphisms, diagnosis and novel therapy

Lactose intolerance is a common disorder affecting an individual's ability to digest lactose present in milk or any food product. Lactose intolerance is caused by the deficiency of β-galactosidase (lactase) in the digestive tract. Diagnosis of lactose intolerance is not so simple and straightforward clinically. Many biochemical and genetic tests have been developed for the determination of lactose intolerance. Several case reports indicate wherein subjects have self-diagnosed being lactose intolerant. There is an emerging link of this disorder with human gene polymorphism, where genetic basis has been used as a diagnostic tool. The high prevalence of this condition among children and adults has compelled the production of lactose-free foods. Additionally, external enzyme supplementation has been looked at as an alternative protective mechanism in lactose intolerant subjects. This review highlights the genetic variants of lactase polymorphism and theranostic (therapeutic and diagnostic) strategies for lactose intolerance.Biomedical Reviews 2014; 25: 35-44

The impact of antioxidant diets, nutraceuticals and physical activity interventions in the prevention of cardiometabolic diseases: An overview

Hippocrates - Father of Medicine (ca 460-370 BC) - endorsed the cuative effects of foods; he said: "Leave your drugs in the chemist's pot if you can heal the patient with food". This review focuses on the management of cardio-metabolic diseases (CMDs) with nutraceuticals and antioxidant diets such as Allium sativum, turmeric, soybean, peptides, phytosterols, resveratrol, polyphenolic substances etc. CMDs are a cluster of conditions linked to altered fat and carbohydrate metabolism as well as macroand micro-vascular problems. CMDs cause severe pathophysiological and metabolic alterations in the body, resulting in the occurrence of chronic diseases like atherosclerosis, coronary heart disease and stroke, neurodegenerative ailments, fatty liver, kidney malfunction, hypercholesterolaemia, hyperlipidaemia, insulin resi-tance and some cancers, consequently imposing a very high economic burden on the healthcare costs. Currently used pharmacotherapies are not only expensive but also are associated with undesirable adverse events. Thus, there is an urgent need for affordable, cost-effective and alternative safe therapies for the prevention and management of CMDs. Holistic approaches targeted for health promotion and prevention of CMDs include the intake of antioxidant-rich diets, anti-inflammation wholesome foods and moderate physical activity (about 30 min/day). Such strategies will not only prevent obesity-related CMDs, type 2 diabetes mellitus (T2DM), coronary heart disease and stroke, but also will improve the quality of patient's life and consequently reduce healthcare burdens. Nutraceuticals and probiotics exhibit anti-inflammation, anti-aging, anti-obesity and anti-diabetic effects, thereby reducing the adverse health risks associated with CMDs. Antioxidants protect cell membranes and DNA from excessive free radicals, which contribute to CMD related diseases. Physical exercise along with dietary interventions helps to mitigate oxidative stress, improve blood triglyceride levels, increase HDL-cholesterol and reduce LDLcholesterol and reverse the biological markers associated with CMDs. Many studies have provided robust scientific evidence and demonstrated links between dietary interventions, nutraceuticals, probiotics, wholesome foods and physical activity for the prevention of CMDs. The major limitations in promoting nonpharmacological therapies for health and well-being benefits are a lack of public awareness and a paucity of clinical nutrition instruction for medical students on the merits of complementary methods for the prevention and management of CMDs. The goals of this review are to provide up-to-date knowledge about selected nutraceuticals, wholesome foods and physical activity in the prevention of CMDs and the underlying mechanisms associated with each intervention, which will ultimately improve patient's quality of life and assist in reducing healthcare costs globally

Coding roles of long non-coding RNAs in breast cancer: Emerging molecular diagnostic biomarkers and potential therapeutic targets with special reference to chemotherapy resistance

Dysregulation of epigenetic mechanisms have been depicted in several pathological consequence such as cancer. Different modes of epigenetic regulation (DNA methylation (hypomethylation or hypermethylation of promotor), histone modifications, abnormal expression of microRNAs (miRNAs), long non-coding RNAs, and small nucleolar RNAs), are discovered. Particularly, lncRNAs are known to exert pivot roles in different types of cancer including breast cancer. LncRNAs with oncogenic and tumour suppressive potential are reported. Differentially expressed lncRNAs contribute a remarkable role in the development of primary and acquired resistance for radiotherapy, endocrine therapy, immunotherapy, and targeted therapy. A wide range of molecular subtype specific lncRNAs have been assessed in breast cancer research. A number of studies have also shown that lncRNAs may be clinically used as non-invasive diagnostic biomarkers for early detection of breast cancer. Such molecular biomarkers have also been found in cancer stem cells of breast tumours. The objectives of the present review are to summarize the important roles of oncogenic and tumour suppressive lncRNAs for the early diagnosis of breast cancer, metastatic potential, and chemotherapy resistance across the molecular subtypes

Obesity related alterations in pharmacokinetics and pharmacodynamics of drugs: emerging clinical implications in obese patients - part II

Key words: ADME, overweight, obesity, pharmacokinetics, pharmacodynamics, drug dose adjustment, obese patient

Perspectives on nanofiber dressings for the localized delivery of botanical remedies in wound healing

Based on their antiseptic and anti-inflammatory properties, plant-derived remedies and herbal products have been used since ancient times for wound and burn cure as well as for treating chronic skin diseases like dermatitis and eczema. Biocompatible and biodegradable polymer nanofiber devices are currently fabricated using sophisticated engineering techniques. Such nanofiber structures have proven efficacious for the localized delivery of therapeutic agents for the treatment of wounds due to their unique physical-chemical properties such as large surface-area-to-volume ratio, high porosity, improved cell adherence, cellular proliferation and migration, as well as controlled in vivo biodegradation rates. The remit of this communication is to highlight the methodology used for the fabrication of nanofiber mats and dressings for the localised delivery of herbal products and plant-derived ingredients for wound healing

Obesity related alterations in pharmacokinetics and pharmacodynamics of drugs: emerging clinical implications in obese patients - part I

Obesity is escalating among children and adults all over the world. This non-communicable disorder contributes heavily to se­vere morbidity and mortality in humans due to the occurrence of diabetes mellitus, cardiovascular diseases, osteoarthritis, and some cancers. Excess deposition of white adipose tissue in obese patients produces hormone like bioactive substances that pro­duce inflammatory cytokines, atherosclerosis and cardiovascular diseases, to name a few. Obesity can also cause pathophysiolo­gal changes in liver, kidney, and GI tract that can affect drug disposition, resulting in therapeutic failure or toxic drug reactions. Alterations in drug absorption, distribution, metabolism and excretion (ADME), ie. pharmacokinetics (PK) and pharmacodynam­ics (PD) have been observed in lean and obese patients. A limited number of studies have shown significant differences in the PK parameters such as Vd, CL, t1/2, Tmax, Cmax, and AUC of drugs (e.g., antimicrobials, chemotherapeutics, anesthetics, CNS agents) in obese and lean patients. In view of these observations, clinical responses to medications can markedly differ between non-obese and obese patients, and this phenomenon can lead to improper dosing, often leaving obese patients mistreated for their ailments. Morbidly obese patients are more likely to wake up during surgical interventions done under general anesthesia, es­pecially propofol. It is therefore imparative that the loading and maintinance dose of drugs, especially anesthetics and lipophilic agents, should be adjusted in obese patients. Further, obese men, women and children should be enrolled in clinical trials to determine the safety and efficacy of pharmaceuticals. The focus of this review is to highlight the relationship of obesity-related alterations in drug ADME and to provide an updated overview about the PK and PD changes observed for a wide spectrum of drugs in obese and non-obese patients. Literature-based recommendations for rational therapeutic dose-modifications are also provided in the publication.Keywords: absorption, distribution, metabolism, excretion (ADME), overweight, obesity, pharmacokinetics, pharmacodynam­ics, drug dose adjustment, obese patient

Therapeutic roles of antioxidant and nutraceuticals in the prevention and management of Alzheimer’s disease: A systematic review

Alzheimer’s disease (AD) has emerged as a serious and challenging neurological disorder in the ageing population worldwide. The progressive decline of mental health in AD patients causes memory loss, cognition decline, and motor impairment, which impacts adversely on the quality of life of afflicted individuls. Health care costs of mental diseases, dementia and AD are escalating globally, because the AD patients need continuous attention either by the family members or by the health care providers. Also, pharmaceutical treatment and hospital cost of AD is very expensive for the society. Therefore,  there is an urgent need to develop cost-effective, affordable, and safe alternative remedies for the prevention/mitigation and management of AD. Plant-derived anti-oxidant/anti-inflammation macromolecules (e.g., curcumin, genistein, melatonin, resveratrol, vanillic acid, caffeic acid, berberine) and nutraceuticals (Gingko Biloba) appear to be the safer and cost-effective promising options for the prevention/progression and management of AD patients. The underlying causes and pathological mechanisms of AD are multiple and complex, which include genetic, epigenetic, non-genetic and environmental risk factors. Lifestyle aspects (e.g., excessive tobacco smoking and alcohol abuse), unhealthy dietary habits, accumulation of heavy metals (arsenic, lead, cobalt, mercury) in CNS, and chronic viral infections are considered some other risk factors in memory loss and AD. Brain has relatively low levels of antioxidants and low repair capacity of neuronal cells. Reduced blood supply and impaired mitochondria promote lesser ATP synthesis and energy support in the brain. Many studies have suggested that excessive oxidative stress in the brain leads to the overproduction of free radicals like reactive oxygen species (ROS) and reactive nitrogen species (RNS) from mitochondrial damage and reduction of ATP synthesis. The unabated over production of ROS/RNS cause insults to brain lipids by intiating lipid peroxidation and damage to cellular molecules, resulting in pathological injury and neuronal death. Antioxidant and anti-inflammation phytomolecules, dietary flavonoids, and nutraceuticals have gained significant importance for scavenging the free radicals and producing neuro-protective and memory-enhancing effects. Systematic searches were done using PUBMED, EMBASE, Scopus, Google Scholar, ResearchGate, and Web of Science databases. Numerous in vitro and in vivo studies have demonstrated that dietary antioxidant/anti-inflammation flavonoids, micronutrients (vitamins, trace metals, amino acids), and plant-derived polyphenols synergistically exhibit neuroprotective activity in AD animal models by stimulating transcription of the endogenous antioxidant system in the brain. The aims and objectives of this review are to recapitulate the current knowledge about the pathophysiology of AD and to shed light on the therapeutic strategies being used for slowing down the progression of dementia and cognitive decline.  We will also provide an overview of the proposed underlying mechanisms of different neutraceuticals and their recommended dosages in the prevention/mitigation of AD along with a summary of the antioxidant/anti-inflammation ingredients present in patented formulations