Amelioration from the ocular irritant Capsaicin: development and assessment of a Capsazepine in situ gel system for ocular delivery.

BACKGROUND: Defense personnel utilize capsaicin-based ocular sprays as non-lethal agents for law implementation during instances of mob violence. This study involves the capsaicin antagonist Capsazepine and the investigation of whether Capsazepine's antagonistic approach can be favorably utilized for defense utilization to block capsaicin-initiated pain and inflammation via the ocular pathway. RESEARCH DESIGN AND METHODS: Ocular capsazepine in situ gels were prepared with polymers Pluronic F-127 and Chitosan; optimized formulation was quantified in ocular tissues chromatographically and by in vivo live ocular imaging; anti-inflammatory efficacy was determined by eye irritation testing, corneal and retinal imaging, ocular prostaglandin estimation, and by viability and proliferation testing using human ocular cell lines, etc. RESULTS: A physicochemically stable Capsazepine in situ gel was formulated which showed little ocular irritation, considerable transcorneal permeation; was precisely quantified in ocular tissues by gas chromatography and in vivo live ocular imaging; showed anti-inflammatory properties against capsaicin by eye imaging experiments, prostaglandin declination and showed acceptable cytocompatibility when studied using human ocular cell lines. CONCLUSIONS: The fabricated in situ Capsazepine gel system might be promising for ocular delivery as it appears a pharmacologically potent and safe development, suitable for utilization in the ocular clinical therapy, provided there is additional research to substantiate it.

Prophylactic efficacy of some chemoprotectants against abrin induced lethality.

Abrin is a highly toxic protein produced by Abrus precatorius. Exposure to abrin, either through accident or by act of terrorism, poses a significant risk to human health and safety. Abrin functions as a ribosome-inactivating protein by depurinating the 28S rRNA and inhibits protein synthesis. It is a potent toxin warfare agent. There are no antidotes available for abrin intoxication. Supportive care is the only option for treatment of abrin exposure. It is becoming increasingly important to develop countermeasures for abrin by developing pre- and post-exposure therapy. The aim of this study is to screen certain pharmaceutical compounds for their chemoprotective properties against abrin toxicity in vivo in BALB/c male mice. Twenty-one compounds having either antioxidant, anti-inflammatory and cyto-protective properties or combination of them, were screened and administered as 1h pre-treatment followed by exposure of lethal dose (2×LD50, intraperitoneally) of abrin. To assess the protective efficacy of the compounds, survival and body weight was monitored. Fifteen compounds extended the survival time of animals significantly, as compared to abrin. The following five of these compounds, namely: Epicatechin-3-gallate, Gallic Acid, Lipoic Acid, GSH and Indomethacin extended the life time ranging from 6 to 9 days. These compounds also attenuated the abrin induced inflammation and enzymes associated with liver function, but none of them could prevent abrin induced lethality. The compounds offering extension of life could be useful to provide a time-window for other supportive treatment and could also be used as combinatorial therapy with other medical countermeasures against abrin induced lethality.

Acute and sub-acute toxicity of an insect pheromone, N-heneicosane and combination with insect growth regulator, diflubenzuron, for establishing no observed adverse effect level (NOAEL).

Aedes aegypti mosquito is one of the most notorious vectors of dangerous diseases like dengue hemorrhagic fever and chikangunya. One method of control of the vectors is by the use of semiochemicals or pheromones. The pheromone n-heneicosane (C21) has been proved to be effective in attracting the female Aedes aegypti to lay eggs in the treated water and the growth of the larva is controlled by insect growth regulator diflubenzuron (DB). This study was planned to assess the safety of C21 alone and the combination with DB. Acute toxicity tests were carried out using two doses, viz., 1600 and 3200 mg/kg and two routes of exposure oral and intra-peritoneal. Dermal toxicity test was carried out in both male and female rats at the dose of 3200 mg/kg. Primary skin irritation test was carried out in rabbits. Sub-acute (90 days) dermal toxicity studies in male and female rats at the dose of 1 and 2 mg/kg via the per-cutaneous route were also studied. Sub-acute (90 days) toxicity test through the oral route was carried out, at doses 125, 250 and 500 mg/kg in male and female rats. The calculated LD50 by ip route and dermal route was more than 5 g/kg in mouse and rats of both the sexes. In the primary skin irritation test no significant changes were noted. In the sub-acute toxicity studies even 500 mg/kg dose was not able to produce toxic response in rats when they were dosed daily for 90 days. The established no observed adverse effect level (NOAEL) was more than 500 mg/kg.

Analgesic and anti-inflammatory activity of amifostine, DRDE-07, and their analogs, in mice.

OBJECTIVES: To find out the analgesic and anti-inflammatory activity, if any, of Amifostine [S-2(3 amino propyl amino) ethyl phosphorothioate], DRDE-07 [S-2(3 amino ethyl amino) ethyl phenyl sulphide] and their analogs DRDE-30 and DRDE-35, the probable prophylactic agent for sulphur mustard (SM). MATERIALS AND METHODS: In order to find out the analgesic activities of the compounds two methods were employed, namely, acetic acid-induced writhing test and formalin-induced paw licking. The persistent pain model of formalin-induced hind paw licking was carried out to test the effect of the compounds on neurogenic pain or early phase (0 to 5 minutes) and on the peripheral pain or the late phase (15 to 30 minutes). To test the effect of the compound in acute inflammation, carrageenan-induced hind paw edema was carried out. This model of inflammation involves a variety of mediators of inflammation. RESULTS: DRDE-07 (81.7%) and DRDE-30 (79.4%) showed significant reduction in the acetic acid-induced writhing test. DRDE-07 (93.1%), DRDE-30 (82%), and DRDE-35 (61.3%) showed significant reduction in the second or late phase of formalin-induced paw licking. All the analogs (more than 60%) including amifostine (43.9%) showed significant reduction of paw edema in the carrageenan-induced paw edema in mice. CONCLUSION: The analgesic and anti-inflammatory activity of the antidotes were comparable with aspirin.