Current Drug Therapy - Volume 7, Issue 1, 2012

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Plant derived gums and mucilage have been used extensively in the pharmaceutical industry as they are nontoxic, stable, and easily available, associated with less regulatory issues as compared to their synthetic counterpart and are inexpensive. They can be easily modified to have tailor-made materials for drug delivery systems. Use of cashew gum, as the scaffold material in formulating hydrogels has been highly pursued owing to the polymer's biocompatibility, low toxicity, and biodegradability. This review focuses its discussion on the Cashew gum (bark exudate from Anacardium occidentale L) as a versatile polymer. It has several unique properties that enable it to be used as an excipient. This review describes the chemical structure, source, extraction procedure and chemical constituents. Accordingly, several investigators have identified its benefits and its vivid application as a gelling agent, polyelectrolyte complexes, viscosity enhancer, controlled delivery systems, surfactants, drying aid agent, coating agent, microencapsulation in various domains. Thus, this novel polymer can become a candidate of major interest in recent years because of its potential applications in several fields.

In 1956, (±)-thalidomide was introduced into the market in Europe as sedative and drug for morning sleeping sickness which resulted into a tragedy called thalidomide tragedy (softenon drama) due to its teratogenic effects in newly born babies. Thalidomide was banned all over the world due to this havoc, which was a big breakdown in the history of this drug. But, in 1998 it resurged after US, FDA approved it for treating Erythema Leprosum Nodosum (ENL). Besides, recently thalidomide and its derivatives showed remarkable property for controlling several malignancies. Thalidomide and its analogues have been used for treating metastatic prostate cancer, multiple myeloma, HIV-related ulcers, Kaposi's sarcoma, weight loss and body wasting associated with HIV. The present article describes the sate-of-art of thalidomide applications with special emphasis on pharmacology, pharmacokinetics, breakdown in the history, break through and resurgence, potential future anticancer drug, potencies of thalidomide vs its analogues, mechanism of anticancer action, different stages and toxicity management. Besides, efforts were also made to predict the future perspectives of thalidomide and its analogues.

Ulcerative colitis is known to cause damage to the liver tissue. Although synthetic and natural substances have been used to prevent liver damage in colitis, little success has been achieved so far. In this study rats were given 120 mg/kg of trinitrobenzene sulfonic acid (TNBS) in order to induce colitis. Protective effects of lycopene and N-Nitro-LArginine Methyl Ester (L-NAME) on oxidative stress and liver damage in colitis were assessed. 91 male Sprague Dawley rats were used in this study. These rats were divided into 12 groups, each consisting of 7 rats, apart from the control group. 1ml of saline was administrated intraperitoneally (i.p) to the rats in the control group, while all the other groups were given TNBS dissolved in 50% ethanol through the intrarectal tract on the first day of the experiment. Groups 1, 2 and 3 were labeled as TNBS groups. 24 hours after the administration of TNBS, rats in groups 4, 5 and 6 were given LNAME, the ones in groups 7, 8, 9 given 1ml/kg olive oil. The remaining groups (10, 11 and 12) were given 5 mg/kg of lycopene i.p. Histological and biochemical analyses were carried out. In liver, tissue damage parameters like edema, sinusoidal dilatation, necrosis, vacuolization and accumulation of inflammatory cells were observed. Evaluation of serum aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) levels, as well as histopathological findings of the liver tissue, show that lycopene has a protective effect upon liver damage due to colitis, and that lycopene is more beneficial to preventing oxidative stress than are olive oil and L-NAME, a synthetic antioxidant substance.

Objective: To describe novel medical therapies in asthma. Data Sources: A comprehensive Pub Med search was performed and studies published between 2000 and 2008 were reviewed. Updated studies from 2009 to 2011 were also included. A focus was placed on randomized, controlled studies. Results: Indacaterol, a once daily inhaled long acting beta 2-agonist (LABA) increased forced expiratory volume in 1 sec (FEV1) and resulted in prolonged bronchodilation. Ciclesonide, a pro-drug inhaled corticosteroid, has been shown to increase FEV1 as well as improve morning, evening, and site-measured peak expiratory flow (PEF) with fewer adverse effects. Fluticasone/formoterol (Flutiform ©), a combination inhaled corticosteroid and LABA, showed a reduction in severe exacerbations requiring hospitalization, increased FEV1, less rescue medication use and higher quality of life scores. Extra-fine beclomethasone with formoterol also appears promising. Several immunomodulating drugs are on the horizon. Roflumilast, an oral once-daily PDE-4 inhibitor, improved forced vital capacity (FVC) and reduced the need for rescue medication. There are encouraging results with mepolizumab and reslizumab, anti-leukin-5 monoclonal antibody preparations, in a specific subset of asthmatic patients. Other approaches such as anti-interleukin-5 receptor blockage and anti-interleukin-9 monoclonal antibodies are in the early stages of development. On the other hand, treatment directed toward anti-tumor necrosis factor in asthmatics has been disappointing. Conclusions: Novel therapies for asthma continue to evolve. Inhaled corticosteroids continue to be at the forefront of treatment. However, combination therapies, novel bronchodilators, and PDE4 inhibitors show promise. Many of these therapies still require further study particularly against the current standards in controller therapy.

With the exception of viral-induced malignances such as cervical cancer, high-affinity proinflammatory T cells specific for tumor-associated antigens (TAA) are either deleted or rendered anergic as a consequence of central and peripheral tolerance. Reprogramming of peripheral blood-derived T cells while preserving their full functional potential to recognize and kill tumor cells is thus required to circumvent negative selection processes. One tactic for redirecting specificity is through genetic modification of T cells to express a chimeric antigen receptor (CAR) targeting a TAA such as CD19, which is expressed on B-lineage malignancies, and their subsequent adoptive transfer into cancer patients. Transposon-based gene transfer is an alternative method to retroviral transduction for integrating such transgenes into the T-cell genome. The Sleeping Beauty (SB) transposon system is a safe and low-cost technique for engineering T cells to express a CD19-specific CAR from a plasmid. This gene-transfer approach provides sufficient transgene integration for retrieval of clinically sufficient numbers of CAR+ T cells for clinical translation into the first-in-human clinical trial already enrolling patients.

The oral route constitutes the preferred route for drug delivery. However, numerous drugs remain poorly available when administered by this route. In order to circumvent this problem, it has been proposed to incorporate drugs successfully to polymeric nanoparticulate systems containing mucoadhesive polymer(s) because of their propensity to interact with the mucosal surface. Peptide drugs are poorly absorbable and are also susceptible to enzymatic degradation in the gastrointestinal tract. In order to overcome physiological and morphological barriers against peptide/poorly absorbable drug delivery, two possible approaches mucopenetrative and/or mucoadhesive properties for drug carriers have been considered. Mucoadhesion can prolong the residence time of drug carriers at the absorption sites, improved drug absorption and controlled drug release from the devices used. The particles with smaller size are likely to diffuse much higher in the mucus layer, provided that diffusion of the particles in the mucus layer obeys the Stokes–Einstein equation. The adhesiveness of the nanoparticles (NPs) in suspension form helps to improve bioavailability and also improves targeting of the parasites persisting in the GIT e.g., Cryptosporidium parvum. Chitosan (CS) based or CS coated NPs represent another common group of mucoadhesive systems and several groups have studied NPs made of these polymers for the enhancement of bioavailability and mucoadhesion of proteins, peptides, and DNA to mucosal tissues. The present review focuses on the gastrointestinal mucoadhesion of NPs for peptide/poorly absorbable drugs. The use of this mucoadhesive NPs delivery system for peptide/poorly absorbable drugs is one of the areas that need to be explored in the future.

Supercooled smectic nanoparticles are under investigation as potential drug carrier systems. Lipid nanoemulsions have the disadvantage of insufficient stabilization whereas solid lipid nanoparticles suffer from disadvantages like low drug incorporation tendencies. Hence there was a need to develop new drug delivery systems which could overcome these disadvantages. Liquid crystalline state also called as mesophase, has macroscopic viscosity and a less orderly state than solids but greater than that of liquids. The liquid crystalline state is classified as nematic and smectic phase. In the smectic phase the molecules are aligned side by side forming a layer and this property of the smectic phase is made use in pharmaceuticals. The various components used include lipid matrices such as cholesteryl esters and stabilizer systems. High- pressure melt homogenization and solvent evaporation are the two widely used methods for their preparation. Drugs, which can be incorporated, are mostly poorly water soluble drugs and drugs which possess very low recrystallization tendencies. In this review an attempt has been made to highlight composition, stabilizer systems, and matrix systems, method of preparation, characterization, applications and safety aspects of the supercooled smectic nanoparticles as drug carrier systems.

This prospective, single centre, open –label study assessed the efficacy, efficiency and tolerability of topical recombinant human platelet –derived growth factor (rhPDGF) in the treatment of chronic ulcers at sites other than the foot in 4 patients with diabetes mellitus. RhPDGF gel 0.01% was applied once daily to the target ulcer in these patients. Efficacy was assessed in terms of ulcer size reduction and efficiency as time to complete healing. Safety was assessed in terms of incidence of adverse events. All ulcers healed completely, of which 2 healed within 2 weeks, 1 by 4 weeks, and 1 by 8 weeks.

This paper reviewed two common sources of elderly incontinence with brain etiologies, “vascular incontinence” (a disorder of bladder control resulting from cerebral white matter disease) and normal-pressure hydrocephalus (NPH), from a neurological point of view. Both diseases manifest with gait disturbance, dementia, and urinary incontinence. Urinary frequency/ urgency (overactive bladder, OAB) often precedes urinary incontinence in both diseases, and in some patients may be the initial manifestation. While NPH is less common than vascular incontinence, at approximately one-tenth the prevalence, it is important because the symptoms can be reversed by shunt surgery or endoscopic third ventriculostomy. For vascular incontinence, early identification of risk factors and initiation of secondary prevention are necessary. Detrusor overactivity due to frontal hypofunction may underlie the bladder disorder in both diseases. Treatment options for urinary incontinence include anticholinergics, which do not easily penetrate the blood-brain barrier, or newer drugs that act on the adrenergic beta-3 receptor and other receptors.