Current Drug Discovery Technologies - Volume 11, Issue 3, 2014

Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored.

Cubosomes are reversed bicontinuous cubic phases and possess unique physicochemical properties. These special systems are receiving much attention for the delivery of various hydrophilic, hydrophobic and amphiphilic drugs with enhanced bioavailability and high loading capacity. A wide variety of drugs are applicable for cubosome formulation for various routes of delivery. The lipids used in cubosome formulation are more stable and offer stability to the formulation during shelf-life. The article reviews about the back ground, techniques of cubosome preparation such as high pressure homogenization, probe ultrasonication and automated cubosome preparation; and also methods of cubosomes preparation such as top down, bottom up and other methods with pictorial presentation. This article emphasizes the phase transition and also targeted approaches of cubosomes. The characterization studies for cubosomes such as cryo transmission electron microscopy, differential scanning calorimetry and scanning electron microscopy followed by in-vitro and in-vivo evaluation studies of cubosomes were explained with appropriate examples. Recent applications of cubosomes were explained with reference to flurbiprofen, odorranalectin, diazepam and dexamethasone. The advantages, disadvantages and limitations of cubosomal technology were emphasized.

Objective: The research aims to formulate and develop the controlled release profile of glibenclamide by encapsulating glibenclamide into niosomes followed by incorporation into an aqueous gel base. Materials and methods: Glibenclamide incorporated niosomes were prepared by a modified ether injection technique using Span 20/Span 80 and cholesterol. The prepared niosomes were evaluated for chemical incompatibility by FT-IR, morphology, vesicle dimension, encapsulation efficiency, in-vitro diffusion and drug release kinetics. Niosomal gels were prepared by incorporating the optimized niosomes into a gel base containing Carbopol 934 and evaluated for viscosity, in-vitro diffusion and in-vivo pharmacodynamic activity. Results and discussion: The results indicated that relationship between the amount of Span and niosomal vesicular diameter was inversely proportional. Microscopic images have illustrated the sphere shape vesicles. The cumulative percentage of drug release from niosomal suspension was observed in the order GN-4GN-2GN- 6GN-5GN-3GN-1. Glibenclamide gel showed highest percentage drug release when compared to niosomal gel. Invivo study revealed that the glibenclamide incorporated niosomal gel formulation; GNG-1 is more efficient in lowering blood glucose levels in experimental animals. Conclusion: The niosomal gel of glibenclamide had released the drug in well controlled manner which is supported by pharmacodynamic activity with evidence of consistent lowering of blood glucose levels.

Curcumin (CUR) is a yellow-coloured polyphenolic compound obtained from the rhizomes of Curcuma longa. In-depth pharmacological screening of curcumin has given the evidence that CUR persuades shielding and curative effects against various cancers, cardiovascular, wound healing effect and neuro disorders etc owning to anti-oxidant, antiproliferative, anti-inflammatory, anti-angiogenic and antimicrobial activities. However, miserable bioavailability due to poor aqueous solubility limits the application of CUR in various ailments. Different methodologies including the nanoparticle technology have been reported for the bioavailability enhancement of CUR. Nanoparticles exhibit not only the improvement in the solubility of CUR and alike lipophilic molecules (resulted in improved bioavailability) but also giving the opportunity for the disease specific cellular and organ targeting. Improved bioavailability and disease based site specific delivery of CUR is more likely to bring it as a safe multifunctional medicine.

We report on a high level of octapeptide matching between HCV, HIV-2, MPV, MUV, EBV, HHV-6, and CMV, and human brain antigens that, when altered, have been specifically associated with neuropathologies such as amyotrophic lateral sclerosis, spinocerebellar ataxia, frontotemporal degeneration, Huntington disease, Parkinson disease, cognitive impairment, aphasia and oculomotor apraxia. Quantitatively, the extent of the viral octapeptide sharing with neurodegeneration- associated proteins is in excess when analyzed in a stochastic expectation context. Qualitatively, two main features characterize the peptide matching: 1) many common sequences are single amino acid repeats, and 2) mostly, the shared octapeptides are part of experimentally validated epitopes, thus suggesting an immune crossreactive potential of the viral peptides shared with brain antigens involved in neurodegeneration. The present study may have relevance for peptidebased therapeutic approaches to block potential autoimmune crossreactions in neurological diseases and dysfunctional behavior.

NVX-108, a dodecafluoropentane-based perfluorocarbon (PFC) emulsion, has therapeutic potential as an oxygen- carrying fluid for emergency medical treatment for traumatic brain injury (TBI) and hemorrhagic shock. Potential cerebral vasoactive properties were assessed by directly measuring pial arteriolar vessel diameters before and after a 30 minute intravenous (IV) infusion of 1.0 ml/kg (high dose [H]) or 0.25 ml/kg (low dose [L]) NVX-108 compared to 2.0 ml/kg Saline (control) in healthy anesthetized rats (N = 6/group). Results showed that post-infusion vessel diameters for small (< 50 µm) and medium (50-100 µm)-sized pial arterioles were significantly (p < 0.05) narrower after only the NVX- 108 H infusion although this vasoconstriction was not statistically significant when analyzed as a percentage change in these vessels. Pial arteriolar vessel diameters were not significantly different for mean value or percentage change after either NVX-108 L or Saline infusions. There were no significant post-infusion changes from baseline in systolic, mean or diastolic blood pressures after any of the treatments although post-infusion blood pressure was statistically higher in the NVX-108 L group compared to NVX-108 H and Saline groups. Arterial blood gases, methemoglob in and lactate were not different from baseline or among groups. No adverse events were observed at either dose of NVX-108. In conclusion, neither 0.25 nor 1.0 ml/kg NVX-108 caused vasoconstriction in cerebral pial arterioles of healthy rats nor resulted in blood pressure changes; the compound should be considered for further investigation for TBI therapy.

Therapeutics designed to increase synaptic neurotransmitter levels by inhibiting neurotransmitter sodium symporters (NSSs) classify a strategic approach to treat brain disorders such as depression or epilepsy, however, the critical elementary steps that couple downhill flux of sodium to uphill transport of neurotransmitter are not distinguished as yet. Here we present modelling of NSS member neuronal GAT1 with the substrate γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter. GABA binding is simulated with the occluded conformation of GAT1 homodimer in an explicit lipid/water environment. Simulations performed in the 1-10 ns range of time elucidated persistent formation of halfextended minor and H-bridged major GABA conformations, referred to as binding and traverse conformations, respectively. The traverse GABA conformation was further stabilized by GAT1-bound Na+(1). We also observed Na+(1) translocation to GAT1-bound Cl- as well as the appearance of water molecules at GABA and GAT1-bound Na+(2), conjecturing causality. Scaling dynamics suggest that the traverse GABA conformation may be valid for developing substrate inhibitors with high efficacy. The potential for this finding is significant with impact not only in pharmacology but wherever understanding of the mechanism of neurotransmitter uptake is valuable.

Candida species are the fourth most common cause of nosocomial bloodstream infections. An increase in the frequency of infections which have become refractory to standard antifungal therapyhave been observed. Recently, the effect of different organochalcogenide compounds reducing both growth and germ tube formation by Candida albicans was demonstrated. This work studied the effect of the organochalcogenide compound (pCl-PhSe)2 on both growth and biofilm formation by Candida albicans. A decrease in C. albicans growth in the presence of crescent concentrations of (pCl- PhSe)2 was observed, in a cell density dependent manner. The inhibition of Candida growth by 10µM (pCl-PhSe)2 was ~60, 57, 47 and 24%, in cell densities of 103, 104, 105 and 106 cells/ml, respectively. The compound (pCl-PhSe)2 was able to inhibit biofilm formation by Candida albicans, when biofilm was performed using a cell density of 106 cells/ml. In addition, an increase in both ROS production (96%) and cell membrane permeability (1.107-fold) by 10 µM (pCl-PhSe)2 was observed in C. albicans.These results demonstrate that the organochalcogenide compound (pCl-PhSe)2 presents a great potential to inhibit both growth and biofilm formation by C. albicans.