Johirul Islam

Mosquito repellents: An insight into the chronological perspectives and novel discoveries

Mosquito being the major medically important arthropod vector; requires utmost attention to reduce the sufferings and economic consequences of those living in the endemic regions. This is only possible by minimising the human-mosquito contact by an absolute preventing measure. However, unfortunately, such absolute measures are yet to be developed despite enormous efforts and huge investments worldwide. In the absence of vaccines for number of mosquito-borne diseases, repellents could be an attractive option for both military personal and civilians to minimise the risk of contacting different mosquito-borne diseases. However, to achieve this golden goal, the detailed knowledge of a particular repellent is must, including its mode of repellency and other relevant informations. Here, in the present article, an effort has been made to convey the best and latest information on repellents in order to enhance the knowledge of scientific community. The review offers an overview on mosquito repellents, the novel discoveries, and areas in need of attention such as novel repellent formulations and their future prospective.

Biocompatible hyperbranched epoxy/silver–reduced graphene oxide–curcumin nanocomposite as an advanced antimicrobial material

Fouling due to bacteria, fungi and algae is a serious problem in the domains of biomedical research, paints and coatings. Toxicity of the prevailing antimicrobial systems demands benign materials with adequate antimicrobial properties. In this context, thermosetting hyperbranched epoxy/silver–reduced graphene oxide–curcumin nanocomposites with antimicrobial attributes against bacteria, fungi and algae are reported here for the first time. The nanocomposite also exhibited high mechanical properties with tensile strength: 54–65 MPa and elongation at break: 17–21%. Ultrasonication, the ‘green’ tool was used to immobilize curcumin onto the silver–reduced graphene oxide nanohybrid. The nanocomposites inhibited the growth of Staphylococcus aureus and Candida albicans, the microorganisms found in surgical infection sites, with minimum inhibitory concentrations of 38 and 41 μg mL−1 at 3% loading of the immobilized nanohybrid. Further, the nanocomposite prevented the growth of the green microalgae Chlorella sp. Moreover, in vitro and in vivo bio-assays confirmed the biocompatibility of the prepared nanocomposite. This study endorses the nanocomposite as an efficient antimicrobial material for different advanced applications from biomedical domains to marine coatings.

Exploration of ethyl anthranilate-loaded monolithic matrix-type prophylactic polymeric patch

Compromised stability of pharmaceutical formulations loaded with volatiles is a serious problem associated with devices designed to deliver volatile compounds. The present study has been focused to evaluate the stability potential of matrix-type polymeric patches composed of volatile ethyl anthranilate for prophylaxis against vector-borne diseases. Ethyl anthranilate-loaded matrix-type polymeric patches were fabricated by solvent evaporation method on an impermeable backing membrane and attached to temporary release liners. Stability testing of the polymeric patches was performed as per the International Conference on Harmonization (ICH) guidelines for 6 months under accelerated conditions. In addition, the quantification of residual solvents was also performed as per the ICH guidelines. After conducting the stability studies for 6 months, the optimized patches showed the best possible results with respect to uniformity of drug content, physical appearance, and other analytical parameters. Furthermore, the amount of residual solvent was found well below the accepted limit. Thus, the present report outlined the analytical parameters to be evaluated to ensure the stability of a certain devices consisting of volatile compounds.

Subchronic dermal exposure to T-2 toxin produces cardiac toxicity in experimental Wistar rats:

Our study aimed to determine the cardiac toxicities of T-2 toxin, a representative mycotoxin that frequently contaminates maize, cereals, and other agricultural products, harvested and stored under damp and cold conditions. Dermal exposure to T-2 toxin caused severe cardiotoxicity in experimental Wistar rats. Electrocardiography studies showed the conduction abnormalities including prolongation of the QT and corrected QT interval, shortening of the PR interval, and tachycardia. Biochemical studies also reported the toxicity of T-2 toxin. T-2 toxin induced acute cardiotoxicity in rats and characterized by significant (p < 0.05) elevation of serum troponin I, creatine kinase (CK) isoenzyme MB, CK isoenzyme NAC, and lactate dehydrogenase as compared to control rats. It is concluded that cardiotoxicity effects of T-2 toxin are thought to be due to direct action on electrocardiac potentials and biochemical changes.

Protection against mosquito vectors Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus using a novel insect repellent, ethyl anthranilate

Growing concern on the application of synthetic mosquito repellents in the recent years has instigated the identification and development of better alternatives to control different mosquito-borne diseases. In view of above, present investigation evaluates the repellent activity of ethyl anthranilate (EA), a non-toxic, FDA approved volatile food additive against three known mosquito vectors namely, Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus under laboratory conditions following standard protocols. Three concentration levels (2%, 5% and 10% w/v) of EA were tested against all the three selected mosquito species employing K & D module and arm-in-cage method to determine the effective dose (ED50) and complete protection time (CPT), respectively. The repellent activity of EA was further investigated by modified arm-in-cage method to determine the protection over extended spatial ranges against all mosquito species. All behavioural situations were compared with the well-documented repellent N,N-diethylphenyl acetamide (DEPA) as a positive control. The findings demonstrated that EA exhibited significant repellent activity against all the three mosquitoes species. The ED50 values of EA, against Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus were found to be 0.96%, 5.4% and 3.6% w/v, respectively. At the concentration of 10% w/v, it provided CPTs of 60, 60 and 30min, respectively, against Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus mosquitoes. Again in spatial repellency evaluation, EA was found to be extremely effective in repelling all the three tested species of mosquitoes. Ethyl anthranilate provided comparable results to standard repellent DEPA during the study. Results have concluded that the currently evaluated chemical, EA has potential repellent activity against some well established mosquito vectors. The study emphasizes that repellent activity of EA could be exploited for developing effective, eco-friendly, acceptable and safer alternative to the existing harmful repellents for personal protection against different hematophagous mosquito species.

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

Abstract 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.

Behavioural and Electrophysiological Responses of Mosquito Vectors Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus to an Ethyl Ester: Ethyl 2-aminobenzoate

Mosquito control using different methods remains an integral component of intervention programmes which aim to protect humans from various mosquito-borne diseases. The host seeking behaviour of mosquitoes is essentially guided by odorant receptor neurons housed in the antenna, maxillary palps and proboscis. The odorant receptor neurons are responsible for detecting chemical cues from hosts and also useful for developing sustainable mosquito-control strategies that exploit host-seeking behaviours. The present investigation evaluates host seeking behavioural responses of a novel, non-toxic and environment friendly repellent, ethyl 2-aminobenzoate against three known vector species of mosquitoes viz. Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus maintained in laboratory. The flight orientation of the test mosquitoes was studied using Y-tube olfactometer, whereas the antennae of adult female mosquitoes were used to investigate the effect of ethyl 2-aminobenzoate on the peripheral olfactory system using electroantennogram (EAG). The findings demonstrate that ethyl 2-aminobenzoate exhibited significant response in Y-tube olfactometer against all the three known vector species of mosquitoes. However, only Anopheles stephensi significantly elicited responses in EAG experiments, while the responses obtained for Aedes aegypti and Culex quinquefasciatus were not statistically significant. The results conclude that currently evaluated chemical ethyl 2-aminobenzoate has potential against some well established mosquito vector species and could be exploited to develop new and comparatively more effective anti-mosquito formulations.

Validated RP-HPLC/DAD Method for the Quantification of Insect Repellent Ethyl 2-Aminobenzoate in Membrane-Moderated Matrix Type Monolithic Polymeric Device

A simple, accurate and sensitive reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed for the estimation of ethyl 2-aminobenzoate (EAB) in a matrix type monolithic polymeric device and validated as per the International Conference on Harmonization guidelines. The analysis was performed isocratically on a ZORBAX Eclipse plus C18 analytical column (250 × 4.4 mm, 5 μm) and a diode array detector (DAD) using acetonitrile and water (75:25 v/v) as the mobile phase by keeping the flow-rate constant at 1.0 mL/min. Determination of EAB was not interfered in the presence of excipients. Inter- and intra-day relative standard deviations were not higher than 2%. Mean recovery was between 98.7 and 101.3%. Calibration curve was linear in the concentration range of 0.5-10 µg/mL. Limits of detection and quantification were 0.19 and 0.60 µg/mL, respectively. Thus, the present report put forward a novel method for the estimation of EAB, an emerging insect repellent, by using RP-HPLC technique.

Exploration of toxicological impacts following acute and sub-chronic exposure to ethyl anthranilate-loaded mosquito repellent patch

ABSTRACT In the recent years, growing concern about the potential toxicity of synthetic repellents has led to the development of environmentally safe non‐toxic insect control methods. Present investigation explores the toxicological impacts of ethyl anthranilate‐loaded mosquito repellent patch (EAMRP) on respiratory system following acute and sub‐chronic inhalation exposure in Wistar rats. Lungs parameters such as enhanced pause, tidal volume, respiration rate, inspiration time, and expiration time were determined using whole body plethysmograph. X‐ray, scanning electron microscopy and histology were utilized to study the morphology and microscopical architecture of lungs. Hematological and serum biochemical markers were estimated. Cytokines such as IL‐1&bgr;, IL‐2, and IL‐12 were also estimated in bronchoalveolar lavage fluid using ELISA kits. Finally, acute oral and dermal toxicity studies were carried out to study the accidental or intentional poisoning due to the ingestion and skin contact of EAMRP, respectively. The findings demonstrate that inhalation exposure to EAMRP did not pose any significant dose related toxicity in above mentioned experiments. Further, no appreciable toxicity was observed in both acute oral and dermal exposure. Thus, these results revealed the non toxic nature of EAMRP in preclinical studies. Hence, EAMRP can be used successfully as an alternative to existing synthetic repellents without any potential health hazards. HIGHLIGHTSToxicological impacts of ethyl anthranilate‐loaded mosquito repellent patch (EAMRP) on respiratory system were explored.Acute oral and dermal toxicity studies were also performed on experimental animals.No appreciable toxicity was observed following acute and sub‐chronic exposure.Results suggest that EAMRP could serve as an ideal mosquito repellent formulation.

Safety evaluation of an oat grain alkaloid gramine by genotoxicity assays

Abstract Gramine is a natural indole alkaloid that has been isolated from different raw plants occurring mainly in Avena sativa, etc. The study was aimed to investigate the possible in vitro antioxidant, in vitro mutagenic, in vitro antimutagenic, and in vivo genotoxic activity of gramine using ferric reducing ability of plasma (FRAP) assay, Metal chelating, Ames bacterial reverse mutation test, and the mouse bone marrow micronucleus assay as well as chromosomal aberration. Four concentrations of gramine viz. 250, 500, 1000, and 2000 μg/mL were evaluated for its antioxidant activity in FRAP Assay and Metal Chelating Test. Four concentrations of gramine (1250 μg/plate, 2500 μg/plate, 5000 μg/plate, and 10 000 μg/plate) were employed in Salmonella typhimurium strains to study the mutagenicity in the presence and absence of standard mutagens, 2-aminofluorene (2-AF), sodium azide (SA), and 2-nitrofluorene (2-NF). Three doses, i.e. 0.1, 0.2, and 0.3 × the LD50 of gramine (i.e. 50 mg/kg, 100 mg/kg, and 150 mg/kg) were administered orally to either sex of Swiss albino mice for 48 h to study the genotoxic activity in micronucleus assay as well as chromosomal aberration. Gramine showed potent antioxidant activity in both the assay. Gramine at the given dose lacks mutagenicity as well as found to possess antimutagenic efficacy. Interestingly, S9 enzymes increase the antimutagenic activity in a dose-dependent manner. There was no significant increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs), as well as no significant difference in the percentage of chromosomal aberrations was observed between the gramine groups and the negative groups but percentage of polychromatic erythrocytes (PCEs) is found to be higher in all the gramine groups. These results indicate significant antioxidant, non-mutagenic as well as non-genotoxic activity of gramine in vitro and in vivo in the given doses.