Isolation of Bluetongue Virus 24 from India - An Exotic Serotype to Australasia.

Bluetongue (BT) is a viral disease of ruminants and is caused by different serotypes of bluetongue virus (BTV), which is transmitted by several species of Culicoides midges. The disease is endemic in tropical areas, and incursions have been observed in some of the temperate areas. Twenty-seven recognized serotypes of BTV have been reported so far. Some serotype viruses have been shown to circulate in certain geographical areas. BTV-24 has been reported from Africa, the Mediterranean and the Americas, whereas it is exotic to Australasia. Here, we report isolation of BTV-24 from India and show that it has high sequence homology in genome segment 2 with other Western isolates of BTV-24. Entry of this serotype into Australasian region is a cause of concern.

Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery.

Transdermal drug delivery (TDD) is the administration of therapeutic agents through intact skin for systemic effect. TDD offers several advantages over the conventional dosage forms such as tablets, capsules and injections. Currently there are about eight drugs marketed as transdermal patches. Examples of such products include nitroglycerin (angina pectoris), clonidine (hypertension), scopolamine (motion sickness), nicotine (smoking cessation), fentanil (pain) and estradiol (estrogen deficiency). Since skin is an excellent barrier for drug transport, only potent drugs with appropriate physicochemical properties (low molecular weight, adequate solubility in aqueous and non-aqueous solvents, etc) are suitable candidates for transdermal delivery. Penetration enhancement technology is a challenging development that would increase significantly the number of drugs available for transdermal administration. The permeation of drugs through skin can be enhanced by physical methods such as iontophoresis (application of low level electric current) and phonophoresis (use of ultra sound energy) and by chemical penetration enhancers (CPE). In this review, we have discussed about the CPE which have been investigated for TDD. CPE are compounds that enhance the permeation of drugs across the skin. The CPE increase skin permeability by reversibly altering the physicochemical nature of the stratum corneum, the outer most layer of skin, to reduce its diffusional resistance. These compounds increase skin permeability also by increasing the partition coefficient of the drug into the skin and by increasing the thermodynamic activity of the drug in the vehicle. This review compiles the various CPE used for the enhancement of TDD, the mechanism of action of different chemical enhancers and the structure-activity relationship of selected and extensively studied enhancers such as fatty acids, fatty alcohols and terpenes. Based on the chemical structure of penetration enhancers (such as chain length, polarity, level of unsaturation and presence of some special groups such as ketones), the interaction between the stratum corneum and penetration enhancers may vary which will result in significant differences in penetration enhancement. Our review also discusses the various factors to be considered in the selection of an appropriate penetration enhancer for the development of transdermal delivery systems.

Optimization of a vehicle mixture for the transdermal delivery of melatonin using artificial neural networks and response surface method.

The objective of this study was to optimize a suitable vehicle composition, using response surface method (RSM) and artificial neural networks (ANN), for the transdermal delivery of melatonin (MT). MT is a hormone produced by the pineal gland that influences mammalian sleep and reproductive patterns. A successful treatment for sleep disorders can be developed if MT is delivered with a rate at which it is produced in the body (endogenous rhythm). Prominent hepato-gastrointestinal first-pass metabolism and short half-life of MT in the body, limits the ability of oral route to mimic the endogenous rhythm. Transdermal route is supposed to avoid first-pass metabolism, and maintain steady-state plasma MT concentrations for a required period of time. However, MT by itself can not pass through the dense lipophilic matrix of stratum corneum. Hence solvents like water (W), ethanol (E), propylene glycol (P), their binary and ternary mixtures were employed to increase MT flux and reduce lag time. Special quartic model (RSM) and deltaW:P (50:50) were predicted as the effective vehicles. W:E:P was considered as the best vehicle, both in terms of flux (12.75 microg/cm(2) per h) and lag time (5 h). RSM and ANN prediction of the best mixtures coincided very well. The ability of these tools to summarize various responses (solubility, flux, and lag time) with respect to vehicle composition enabled us to study the inter-relativity between the responses.

Effect of fatty acids on the permeation of melatonin across rat and pig skin in-vitro and on the transepidermal water loss in rats in-vivo.

Transdermal delivery of melatonin would be advantageous in the treatment of sleep disorders considering the short biological half-life of melatonin and its variable bioavailability via the oral route. This study looked at suitable penetration enhancers for the transdermal permeation of melatonin. The permeation of melatonin was enhanced by all saturated and unsaturated fatty acids across both rat and porcine skin. There was a parabolic relationship between the carbon chain length of saturated fatty acids and the enhancement of melatonin permeation across rat and porcine skin. For rat skin, the maximum flux was observed with undecanoic acid (45.33 microg cm(-2) h(-1)) which enhanced the flux of melatonin 8.6 times compared with the control, whereas lauric acid produced the maximum flux of melatonin (24.98 microg cm(-2) h(-1); 4-7 times) across porcine skin. An increase in the number of double bonds in cis-9-octadecanoic acid increased the flux of melatonin across rat skin. In contrast, with porcine skin, the flux of melatonin decreased as the number of double bonds increased, although the flux values were not statistically significant. Treatment of rats with undecanoic acid, oleic acid and linolenic acid for 3 h using Hill top chamber enhanced the transepidermal water loss significantly. The maximum transepidermal water loss was observed with undecanoic acid and linolenic acid among saturated and unsaturated fatty acids, respectively. Nonanoic acid and myristic acid did not cause a significant change in the transepidermal water loss. The enhancement effect of saturated fatty acids on the permeation of melatonin was dependent on the chain-length of the fatty acid in both rat and porcine skin. While an increase in the number of double bonds in the fatty acid increased the flux of melatonin in rat skin, no significant difference in the flux was observed with porcine skin. The permeation enhancement of melatonin by saturated and unsaturated fatty acids across rat skin was significantly higher than that of porcine skin. A positive correlation was observed between the permeation enhancement effect of the fatty acids across rat skin in-vitro and the transepidermal water loss in rats in-vivo, suggesting that there is a similarity in the mechanism by which fatty acids enhance the permeation of melatonin and in the enhancement of transepidermal water loss. We conclude that saturated fatty acids such as undecanoic acid or lauric acid which showed maximum permeation across rat and porcine skin, respectively, may be used as potential penetration enhancers in the development of a transdermal delivery system for melatonin.