The fabrication and assessment of mosquito repellent cream for outdoor protection.

Mosquito-borne infections like dengue, malaria, chikungunya, etc. are a nuisance and can cause profound discomfort to people. Due to the objectional side effects and toxicity associated with synthetic pyrethroids, N,N-diethyl-3-methylbenzamide (DEET), N,N-diethyl phenylacetamide (DEPA), and N,N-di ethyl benzamide (DEBA) based mosquito repellent products, we developed an essential oil (EO) based mosquito repellent cream (EO-MRC) using clove, citronella and lemongrass oil. Subsequently, a formulation characterization, bio-efficacy, and safety study of EO-MRC were carried out. Expression of Anti-OBP2A and TRPV1 proteins on mosquito head parts were studied by western blotting. In-silico screening was also conducted for the specific proteins. An FT-IR study confirmed the chemical compatibility of the EOs and excipients used in EO-MRC. The thermal behaviour of the best EOs and their mixture was characterized by thermogravimetric analysis (TGA). GC-MS examination revealed various chemical components present in EOs. Efficacy of EO-MRC was correlated with 12% N,N-diethyl benzamide (DEBA) based marketed cream (DBMC). Complete protection time (CPT) of EO-MRC was determined as 228 min. Cytotoxicity study on L-132 cell line confirmed the non-toxic nature of EO-MRC upon inhalation. Acute dermal irritation study, acute dermal dose toxicity study, and acute eye irritation study revealed the non-toxic nature of EO-MRC. Non-target toxicity study on Danio rerio confirmed EO-MRC as safer for aquatic non-target animals. A decrease in the concentration of acetylcholinesterase (AChE) was observed in transfluthrin (TNSF) exposed Wistar rats. While EO-MRC did not alter the AChE concentrations in the exposed animals. Results from western blotting confirmed that Anti-OBP2A and TRPV1 proteins were inhibited in TNSF exposed mosquitoes. Mosquitoes exposed to EO-MRC showed a similar expression pattern for Anti-OBP2A and TRPV1 as the control group. In silico study revealed eight identified compounds of the EOs play significant roles in the overall repellency property of the developed product. The study emphasizes the mosquito repellent activity of EO-MRC, which could be an effective, eco-friendly, and safer alternative to the existing synthetic repellents for personal protection against mosquitoes during field conditions.

Essential oil based controlled-release non-toxic evaporating tablet provides effective repellency against Musca domestica.

Housefly, Musca (M) domestica L. (Diptera: Muscidae) is a pervasive insect that transmits a variety of pathogens to humans and livestock. Although numerous synthetic pesticides are available to combat houseflies, their ecological and toxicological concerns have led to the exploration of natural products as safer alternatives. The present work was designed to develop an essential oil based controlled-release evaporating tablet (EO-CRT) and investigate its repellency against M. domestica. This study assesses the toxicological impacts of the EO-CRT following its sub-chronic inhalation exposure. Briefly, repellent activity of fourteen essential oils viz. lemon grass, bergamot, mentha, basil, camphor, lavender, clove, patchouli, rosemary, cinnamon, eucalyptus, citronella, jasmine and wild turmeric against M. domestica were screened using the 'Y'-tube olfactometer. The synergistic activity of the best four oils, under preliminary screening, were further evaluated by double and triple blending. The best combination of three oils were finalized for optimization with 17-run, 3-factor, 3-level Box-Behnken design. This was then employed to construct polynomial models and predict the best optimized formulation EO-CRT. EO-CRT was characterized by Differential Scanning Calorimetry (DSC) and Gas Chromatography-Mass Spectroscopy (GC-MS). The efficacy of the EO-CRT against M. domestica was assessed by attraction and repellent assay. Chest X-ray, histopathology and scanning electron microscopy of the exposed lung was performed to study EO-CRT's sub-chronic toxicity on Wistar rats. The EO-CRT showed slow release up to a period of 10 days at room temperature, exhibited 100% repellency (%Error=1.237) against M. domestica and was found to possess all the characteristics of an ideal formulation. Sub-chronic toxicity study further revealed the non-toxic nature of the EO-CRT. Thus, our study provides an assurance that the formulated EO-CRT could be effective not only in repelling the nuisance pest, M. domestica, in human dwellings, but also in minimizing the mechanical transmission of pathogens by it.

Design, development and assessment of an essential oil based slow release vaporizer against mosquitoes.

Mosquitoes (Diptera; Culicidae) are a biting nuisance and are of economic and health importance, especially for people living in tropical countries like India. Given the environmental concerns and health hazards of synthetic insecticides, development of natural products for the control of mosquito and mosquito-borne diseases are needed. In view of this, an essential oil based novel liquid vaporizer formulation with citronella and eucalyptus oils has been developed using a computer aided Artificial Neural Network and Particle Swarm Optimization (ANN-PSO) algorithm approach, aiming to predict the best optimized formulation (OF). Following the development, OF was characterized by Fourier Transform-Infra Red (FT-IR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS). The efficacy of the OF was assessed against two major mosquito vectors viz. Anopheles stephensi and Aedes albopictus using a Peet-Grady chamber. Finally, toxicological impacts of the OF following its inhalation were investigated as per the Organization for Economic Co-operation and Development (OECD) guidelines. The results revealed all the ideal characteristics of the OF which were found to provide a slow release of up to 450 h at room temperature. Most importantly, the OF, exhibited 50% mosquito knock down (KT50) within 11.49±1.34 and 14.15±2.15 min against An. stephensi and Ae. albopictus respectively. Toxicity assessment showed a non toxic nature of the OF following inhalation. Thus the present development would be beneficial for controlling both An. stephensi and Ae. albopictus without any associated health hazards.

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.

Fundamental pharmacological expressions on ocular exposure to capsaicin, the principal constituent in pepper sprays.

Eye irritation assessment is compulsory to anticipate health risks in military personnel exposed to riot control agents such as capsaicin, the principal constituent of oleoresin capsicum, or pepper sprays. The present work investigates certain fundamental yet unaddressed pharmacological manifestations on ocular exposure to capsaicin. Ocular pharmacology of capsaicin was studied using acute eye irritation (AEI), bovine corneal opacity and permeability (BCOP) assay, corneal fluorescein staining and indirect ophthalmoscopy studies, transcorneal permeation, Schirmer tear secretion test, nerve conduction velocity study and enzyme-linked immunosorbent assay (ELISA). Additionally, histopathology and scanning electron microscopy (SEM) of bovine corneas and rat optic nerves were done to further estimate capsaicin induced morphological variations. Our findings demonstrated that AEI, BCOP, corneal fluorescein staining and indirect ophthalmoscopy were useful in assessing capsaicin induced ocular irritation; AEI and BCOP also contributed towards indicating the eye irritation potential of capsaicin as per the United Nations Globally Harmonized System of Classification and Labelling of Chemicals categorization. Additional experimental observations include considerable transcorneal permeation of capsaicin, capsaicin induced reduction in tear secretions and nerve conduction velocity and increased expression of proinflammatory cytokines by ELISA. Histopathology and SEM were favourable techniques for the detection of capsaicin induced ocular physiological modifications.

Safety profile of silver sulfadiazine-bFGF-loaded hydrogel for partial thickness burn wounds.

In the present investigation, the safety of novel combinational silver sulfadiazine-bFGF-loaded hydrogel was assured by performing acute skin irritation, sensitization, acute dermal toxicity, and eye irritation in compliance with the Organization for Economic Co-operation and Development guidelines. In the skin irritation study, placebo, test, and positive control (0.8% w/v aqueous solution of formaldehyde) were applied on New Zealand rabbits and monitored for abnormal skin responses including erythema and edema. The placebo and test formulation did not induce any adverse reactions and were classified as nonirritating materials. In the skin sensitization test, guinea pigs were sensitized by positive control (0.1% w/v 1-chloro-2,4-dinitrobenzene in 10% of propylene glycol as a standard skin sensitizing agent), placebo, and test formulations. Weak sensitization was observed in the placebo and test formulation treated groups. Additionally, acute dermal toxicity test was performed in Wistar rats, where no signs of toxicity were observed in biochemical, hematological, and histopathological studies. Moreover, the acute eye irritation test was carried out in rabbits and no abnormal clinical signs were evident in the cornea or iris. As a whole, these findings suggest that the hydrogel formulation does not cause any skin irritation, skin sensitizationand dermal toxic effects, and eye irritation following dermal and ocular applications, respectively. Therefore, all the findings obtained from this preclinical study indicated that this hydrogel formulation is nontoxic and safe for use in animal models.

Capsaicin, the primary constituent of pepper sprays and its pharmacological effects on mammalian ocular tissues.

Capsaicin is the principal constituent of oleoresin capsicum, or pepper spray, as it is commonly known. Pepper sprays are frequently used in riot control situations by defence organizations all over the world to deal with uncontrolled civil or criminal disturbances. Although capsaicin is noted for its irritant and inflammatory properties, the ocular profile of capsaicin has not been specifically studied and interpreted. The present review analyses the mammalian opthalmological profile of capsaicin and its pharmacological and toxicological manifestations including capsaicin induced corneal changes, neurogenic inflammation, neuroprotective influences on retinal ganglion cells (RGCs), depletion of neuropeptide content in sensory nerve terminals etc. Substantial views on the capsaicin receptor Transient Receptor Potential Vanilloid V1 (TRPV1), its presence, significance and capsaicin induced mediations have been presented. Studies conducted previously on the reversal of capsaicin evoked ocular responses have been briefly demonstrated. In this regard, TRPV1 antagonists (especially the competitive antagonist Capsazepine) have been indicated as potential candidates in mitigating or alleviating capsaicin elicited ocular responses. The review overall is a comprehensive perspective of the ocular inflammatory and pharmacological responses generated on exposure to capsaicin and concludes suggesting a possible regulatory framework for relief from the same presumably by the employment of specialized and target specific TRPV1 antagonists.

Curcumin-docetaxel co-loaded nanosuspension for enhanced anti-breast cancer activity.

PURPOSE: A curcumin-docetaxel co-loaded nanosuspension with increased anti-breast cancer activity was developed. Curcumin is a potential anticancer agent with p-glycoprotein (p-gp) inhibiting activity may be co-administered with docetaxel as a nanosuspension to enhance its anticancer effect by increasing the oral bioavailability and decreasing drug efflux. METHODS: Nanosuspensions of curcumin and docetaxel were prepared by precipitation-homozenisation technique and evaluated for particle size, polydispersity, zeta potential and drug release. The in vitro MTT assay was conducted using MCF-7 for anti-breast cancer activity. The in vivo biodistribution by radiolabeling and tumor inhibition study was conducted in mice. RESULTS: Homogenous nanosuspensions of 80 ± 20 nm were obtained with increased solubility. The drugs as nanosuspensions showed higher cytotoxicity on MCF-7 cell line compared to their suspensions due to the increased in vitro cellular uptake. Due to this increased solubility, sensitization of tumor cells and inhibition of p-gp the in-vivo results showed greater tumor inhibition rate of up to 70% in MCF-7 treated mice. Histopathological results showed higher apoptotic activity and reduced level of angiogenesis. CONCLUSIONS: The in vitro and in vivo study of the nanosuspensions has shown that Co-administration of Curcumin as a p-gp inhibitor with docetaxel may have the potential to increase the anti-breast cancer efficacy of both drugs.