Kanchan Kohli

Strategy for effective brain drug delivery

Blood-brain barrier (BBB) together with enzymes restricts the entry of substances for maintaining the internal milieu of the brain. Because of the presence of multiple endogenous transporters, BBB allows a selective entry of nutrients and minerals across it and limits the entry of foreign substances like drugs as well as neuropharmaceutical agents. This makes the CNS treatment ineffective. The conventional drug delivery systems which release drug into general circulation fail to deliver drugs effectively to brain and is therefore not very useful in treating certain diseases that affect CNS including Alzheimers disease, dementia, Parkinsons disease, mood disorder, AIDS, viral and bacterial meningitis. Therefore there is a need to develop and design approaches which specifically target to brain in a better and effective way. The present review enlightens about several novel approaches including nanotechnology based approach like nanoparticles, liposomes, antibody mediated delivery approach and application of genomics in brain drug targeting that would give an insight to the researchers, academia and industrialists.

Self-emulsifying drug delivery systems: an approach to enhance oral bioavailability

Self-emulsifying drug delivery systems are a vital tool in solving low bioavailability issues of poorly soluble drugs. Hydrophobic drugs can be dissolved in these systems, enabling them to be administered as a unit dosage form for per-oral administration. When such a system is released in the lumen of the gastrointestinal tract, it disperses to form a fine emulsion (micro/nano) with the aid of GI fluid. This leads to in situ solubilization of drug that can subsequently be absorbed by lymphatic pathways, bypassing the hepatic first-pass effect. This article presents an exhaustive account of various literature reports on diverse types of self-emulsifying formulations with emphasis on their formulation, characterization and in vitro analysis, with examples of currently marketed preparations.

Mechanism of Action of Flavonoids as Anti-inflammatory Agents: A Review

Flavonoids are polyphenolic compounds that occur ubiquitously in plants having a variety of biological effects both in vitro and in vivo. They have been found to have antimicrobial, antiviral, anti-ulcerogenic, cytotoxic, anti-neoplastic, mutagenic, antioxidant, antihepatotoxic, antihypertensive, hypolipidemic, antiplatelet and anti-inflammatory activities. Flavonoids also have biochemical effects, which inhibit a number of enzymes such as aldose reductase, xanthine oxidase, phosphodiesterase, Ca(+2)-ATPase, lipoxygenase, cycloxygenase, etc. They also have a regulatory role on different hormones like estrogens, androgens and thyroid hormone. They have been found to have anti-inflammatory activity in both proliferative and exudative phases of inflammation. Several mechanisms of action have been proposed to explain anti-inflammatory action of flavonoids. The aim of the present review is to give an overview of the mechanism of action of potential anti-inflammatory flavonoids.

Advancement in carbon nanotubes: basics, biomedical applications and toxicity

Objectives  Carbon nanotubes (CNTs) have attracted much attention by researchers worldwide in recent years for their small dimensions and unique architecture, and for having immense potential in nanomedicine as biocompatible and supportive substrates, as a novel tool for the delivery of therapeutic molecules including peptides, RNA and DNA, and also as sensors, actuators and composites.

Curcumin: a natural antiinflammatory agent

Extensive scientific research on curcumin, a natural compound present in the rhizomes of plant Curcuma longa Linn., demonstrated its antiinflammatory action. Curcumin was found to inhibit arachidonic acid metabolism, cyclooxygenase, lipoxygenase, cytokines (Interleukins and tumour necrosis factor) Nuclear factor-kB and release of steroidal hormones. Curcumin was reported to stabilize lysosomal membrane and cause uncoupling of oxidative phosphorylation besides having strong oxygen radical scavenging activity, which was responsible for its antiinflammatory property. In various animal studies, a dose range of 100-200 mg/kg body weight exhibited good antiinflammatory activity and seemed to have negligible adverse effect on human systems. Oral LD50 in mice was found to be more than 2.0 g/kg body weight.

Study of cosurfactant effect on nanoemulsifying area and development of lercanidipine loaded (SNEDDS) self nanoemulsifying drug delivery system.

The present study deals with the development and characterization of self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral bioavailability of poorly soluble third generation calcium channel blocker lercanidipine (LER). Solubility of the LER was estimated in various oils, cosurfactants and surfactants which were grouped into two different combinations to construct pseudoternary phase diagrams. Various thermodynamic stability and dispersibility tests were performed on the formulations from phase diagram. After constructing phase diagram of two different combinations NL-I and NL-II, the effect of cosurfactants on the nanoemulsifying area was studied and the effect of number and length of hydrophobic alkyl chains of cosurfactant in its emulsification capacity was proved. Percentage transmittance, emulsification time, viscosity and droplet size analysis were used to characterize optimized formulations. The optimized formulation composed of Cremophor EL (45% wt/wt), (13.5% wt/wt) Caproyl 90 with (1.5% wt/wt) Transcutol® HP as per limits of inactive ingredients guidelines of FDA and Maisine oil (10% wt/wt). The mean droplet size in selected nanocarrier system was 20.01 nm. The in vitro dissolution profile of LER SNEDDS was found significant in comparison to the marketed LER (Zanidip) tablet and pure drug in pH 1.2, 4.5 and 6.8 buffers. Empty hard gelatin capsule shells were filled using Pfizers Licap technology and charged on stability conditions of 30 °C/65% RH, 40 °C/65%RH and 50 °C/75% in glass bottles where no significant degradation (p>0.05) was observed in 3 months. The results indicate that SNEDDS of LER, owing to nanosized, has potential to enhance the absorption of drug.

Formulation and optimization of nanotransfersomes using experimental design technique for accentuated transdermal delivery of valsartan

UNLABELLED The purpose of this work was to develop and statistically optimize nanotransfersomes for enhanced transdermal of valsartan vis-à-vis traditional liposomes. Nanotransfersomes bearing valsartan were prepared by conventional rotary evaporation method and characterized for various parameters including entrapment efficiency, vesicles shape, size, size distribution, and skin permeation. In vivo antihypertensive activity conducted on Wistar rats was also taken as a measure of performance of nanotransfersomes and liposomes. Nanotransfersomes proved significantly superior in terms of amount of drug permeated in the skin, with an enhancement ratio of 33.97 ± 1.25 when compared to rigid liposomes. This was further confirmed through a confocal laser scanning microscopy study. Nanotransfersomes showed better antihypertensive activity in comparison to liposomes by virtue of better permeation through Wistar rat skin. Finally, it could be concluded that the nanotransfersomes accentuates the transdermal flux of valsartan and could be used as a carrier for effective transdermal delivery of valsartan. FROM THE CLINICAL EDITOR In this paper, the authors discuss the development and optimization of nanotransfersomes for enhanced transdermal of valsartan and demonstrate accentuated transdermal compared to standard preparations.

Chemical penetration enhancers: a patent review

Background: Ever since transdermal drug delivery came into existence, it has offered great promises, although most of them are yet to be fulfilled owing to some intrinsic restrictions of the transdermal route. On the positive side, transdermal drug delivery systems present advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. The greatest hindrance in the percutaneous delivery is the obstruction property of the stratum corneum, the outermost layer of the skin, in addition to usual problems such as skin binding, skin metabolism, cutaneous toxicity and prolonged lag times. Objective: This paper reviews investigations on the feasibility and application of penetration enhancers as described in recent patents, which help in the selection of a suitable sorption promoter(s) for enhanced delivery of medicaments through the skin. Method: The patents granted under various categories of penetration enhancers have been discussed including fatty acids, terpenes, fatty alcohol, pyrrolidone, sulfoxides, laurocapram, surface active agents, amides, amines, lecithin, polyols, quaternary ammonium compounds, silicones, alkanoates and so on. Conclusion: Scores of promising chemicals have been harnessed for their skin permeation promoting capacity as mentioned earlier. In future, many more chemicals and putative enhancers are likely be documented and patented.

Characterization of 5-fluorouracil microspheres for colonic delivery

The purpose of this investigation was to prepare and evaluate the colon-specific microspheres of 5-fluorouracil for the treatment of colon cancer. Core microspheres of alginate were prepared by the modified emulsification method in liquid paraffin and by cross-linking with calcium chloride. The core microspheres were coated with Eudragit S-100 by the solvent evaporation technique to prevent drug release in the stomach and small intestine. The microspheres were characterized by shape, size, surface morphology, size distribution, incorporation efficiency, and in vitro drug release studies. The outer surfaces of the core and coated microspheres, which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged from 22 to 55 μm, and the size of the coated microspheres ranged from 103 to 185 μm. The core microspheres sustained the drug release for 10 hours. The release studies of coated microspheres were performed in a pH progression medium mimicking the conditions of the gastrointestinal tract. Release was sustained for up to 20 hours in formulations with core microspheres to a Eudragit S-100 coat ratio of 1∶7, and there were no changes in the size, shape, drug content, differential scanning calorimetry thermogram, and in vitro drug release after storage at 40°C/75% relative humidity for 6 months.

Enhanced transdermal delivery of an anti-hypertensive agent via nanoethosomes: Statistical optimization, characterization and pharmacokinetic assessment

The aim of the current investigation is to develop and statistically optimize nanoethosomes for transdermal valsartan delivery. Box-Behnken experimental design was applied for optimization of nanoethosomes. The Independent variables were phospholipids 90G (X(1)), ethanol (X(2)), valsartan (X(3)) and sonication time (X(4)) while entrapment efficiency (Y(1)), vesicle size (Y(2)) and flux (Y(3)) were the dependent variables. The optimized formulation obtained was then tested in rats for an in vivo pharmacokinetic study. Results indicate that the nanoethosomes of valsartan provides better flux, reasonable entrapment efficiency, more effectiveness for transdermal delivery as compared to rigid liposomes. Optimized nanoethosomal formulation with mean particle size is 103 ± 5.0 nm showed 89.34 ± 2.54% entrapment efficiency and achieved mean transdermal flux 801.36 ± 21.45 μg/cm(2)/h. Nanoethosomes proved significantly superior in terms of, amount of drug permeated in the skin, with an enhancement ratio of 43.38 ± 1.37 when compared to rigid liposomes. Confocal laser scanning microscopy revealed an enhanced permeation of Rhodamine-Red loaded nanoethosomes to the deeper layers of the skin as compared to conventional liposomes. In vivo pharmacokinetic study of nanoethosomal transdermal therapeutic system showed a significant increase in bioavailability (3.03 times) compared with oral suspension of valsartan. Our results suggest that nanoethosomes are an efficient carrier for transdermal delivery of valsartan.