Insect Repellent Formulations Research Articles

Effectiveness of Plant-based Repellents against different Anopheles Species: a Systematic Review

Abstract: The deadliest pest that humans are aware of is the mosquito. One of the best ways to lower sickness is to avoid mosquito bites. In daily life, we utilize a variety of synthetic mosquito repellents; nevertheless, prolonged use of these repellents can pose health and environmental risks. Many plants have been utilized as fumigants, insecticidal agents, and repellents since ancient times. The majority of plants include phytochemicals that act as insect repellent, shielding them from numerous insect attacks. The study presented in this paper aims to create herbal insect repellent formulations that are both safe and effective. Insecticides used in the past included neem oil, camphor, orange peel powder, and orange seeds. There are numerous applications for the dehydrated peels of citrus fruits in pest management. An effective repellent is orange oil, which is derived from orange peels. Linalool, a widely used flavouring agent and ingredient in perfumes, exhibits insect repellent qualities in addition to its olfactory qualities. Furthermore, it has been included into flammable items and topical therapies. It can be used in place of synthetic repellent because it has little risk of negative effects and benefits human health. The purpose of our study is to look into the phytochemical extracts from herbal products' repelling properties.

A Review on the Comparative Analysis of Synthetic Insect Repellents and Essential Oil Based Sustained-release Insect Repellent Formulations

The necessity of developing insect repellents with highly effective sustained release properties has attracted more attention due to the vast spread of arthropod-borne diseases such as dengue and malaria, which must be controlled with proper measures, and also due to the devastating damage caused by severe infestation of insect pests on crops and stored food. Natural and synthetic insect repellents are used against insect vectors and insect pests. Topical insect repellent formulations should be less toxic, less irritant, and less skin permeable. Irrespective of the type and form of the repellent, the mechanism of action depends on the formation of a vapour barrier/ odour barrier, that would deviate the insect from reaching the host. Synthetic insect repellents are highly efficient but due to their high toxicity, degradation resistance, and bio accumulation, they raise environmental and ecological issues. Due to the adverse effects caused by synthetic insect repellents, more attention is given to insect repellents consisting of natural products.Essential oils are among the widely used natural insect repellents available due to their biocompatibility and non-toxicity. High volatility of essential oils is the major problem that hampers the application of essential oils as insect repellent agents. The high volatility that reduces the length of application, and its activity can be successfully addressed by the formulation of slow-release insect repellent composites by incorporating essential oils into adsorbing or encapsulating matrices. Zeolites, montmorillonite, β-cyclodextrin, polymeric materials, and electrospun nanomaterials are commonly used to develop slow-release formulations with essential oils. Among these, polymeric microcapsules are the most extensively studied and developed slow-release insect repellent systems that are based on natural and synthetic active compounds.
 Key words: Formulation, Insects, Microcapsules, Repellents, Zeolite

Poly(oxyethylene)/Poly(oxypropylene) butyl ether prolongs the repellent effect of N,N-diethyl-3-toluamide on the skin.

N,N-diethyl-meta-toluamide (DEET) is a widely used insect repellent, with minimal skin permeation and sustained repellent activity in the superficial layers of the skin. In this study, we prepared a 10% DEET formulation consisting of 40% ethanol with or without 2% poly(oxyethylene)/poly(oxypropylene) butyl ether (POE-POP), an amphiphilic random copolymer. Further, we demonstrated the effects of POE-POP on tensile stress (stickiness), hydrophobicity, skin retention, permeation, and repellent activity of DEET. Stickiness was measured in male ICR mice (7-week old), and skin retention and permeation were evaluated in male Wistar rats (7-week old). In addition, female Aedes albopictus were used to measure the repellent action of DEET. The addition of POE-POP did not affect stickiness, volatility, and degradability but decreased logP and increased viscosity of DEET. Next, we demonstrated the behavior of DEET formulations in the rat skin. POE-POP prolonged the retention of DEET in the superficial layers of the rat skin (skin surface and stratum corneum) and decreased the penetration of DEET into rat skin tissues (epithelium and dermis). The repellent effect of DEET was also enhanced by the addition of POE-POP. However, severe skin damage was not observed after repetitive treatment with DEET formulations containing POE-POP for one month (twice a day). In conclusion, we demonstrated that a 10% DEET formulation consisting of 40% ethanol and 2% POE-POP attenuated the skin penetration and prolonged the repellent action of DEET without causing stickiness and skin damage. We conclude that the combination of ethanol and POE-POP is useful as a safe and effective delivery system for the development of insect repellent formulations containing DEET.

Development and validation of an analytical method using High Performance Liquid Chromatography (HPLC) to determine ethyl butylacetylaminopropionate in topical repellent formulations

ABSTRACT Diseases caused by insects are frequent in poor countries, leading to epidemic scenarios in urban areas; e.g., Dengue, Zika and Chikungunya. For this reason, the development of a safe and efficient topical formulation is essential. Ethyl butylacetylaminopropionate (EB) is a mosquito repellent developed by Merck, which is used in products for adults, children and especially babies, due to its low allergenic potential. The aim of this work was to validate an analytical methodology to quantify EB in a new poloxamer-based formulation by high-performance liquid chromatography (HPLC). The quantification methodology was performed at 40 oC using a Kromasil reverse-phase column (C18), with the dimensions of 250 x 4.6 mm. The mobile phase was acetonitrile:water (1:1) at a 1.0 mL/min flow-rate. The detector wavelength was set at 218 nm to detect EB. The methodology was considered validated since the results indicated linearity (R2>0.99), specificity, selectivity, precision and accuracy (active recovery between 98% and 102%). It also presented limits of detection and quantification of 0.255 µg/mL and 0.849 µg/mL, respectively. The present study demonstrated the EB vehiculated in poloxamer gel is promising as a new insect repellent formulation, since it could be quantified and quality control evaluated.

Development and characterization of repellent formulations based on nanostructured hydrogels

Diseases caused by insects could lead to epidemic scenarios in urban areas and insect repellents are a shield against a wide range of insects, but they need to be safe without compromising efficacy. Ethyl butylacetylaminopropionate (EB) is a synthetic mosquito repellent, which could be used in products for adults and children due to its low-allergenic potential. The aim of this study was to develop and characterize EB and Poloxamer 407 nanoemulsions regarding their droplets mean size, pH, rheological properties, cytotoxicity and in vitro permeation profile. The developed formulations (F1 with 12.5% of EB and F2 with 25% of EB) were compared with a commercial formulation containing 12.5% of EB. Droplets mean size was determined by DLS, and for both nanoemulsions they were around 200 nm; however, the commercial formulation presented a droplets mean size of 10 nm, which could contribute to its high permeation. F1 and F2 presented a gel-like behavior, however F2 presented lower viscosity due to the presence of more EB between the polymer chains preventing them to interact with each other. Also, F2 was less retained by the epidermis when compared to F1 probably due to its lower viscosity. For the cytotoxicity assay only F2, which presented the highest concentration of EB was tested, and it was not toxic to the cells. This result could be also extended to F1 which presented half the EB concentration. The present study demonstrated that EB and Poloxamer 407 nanoemulsions are promising as new insect-repellent formulations.

Polymer-based Drug Delivery Systems Applied to Insects Repellents Devices: A Review.

Insects-borne diseases constitute a public health concern. Since there is no vaccine or curative treatment for many of these diseases, individual protection is the main approach to prevent them. Nowadays, the search for replacing synthetic molecules for insect repellents from natural sources, such as essential oils, is increasing. However, most of them present low efficiency compared to synthetic repellents. Therefore, decreasing skin permeation of synthetic repellents or yet, increasing effectiveness of natural repellents are challenges that must be overcome during the development of novel insect repellent formulations. In this context, polymer-based formulations allow entrapping active ingredients and provide release control. Encapsulation into polymeric micro/nanocapsules, cyclodextrins, polymeric micelles or hydrogels constitutes an approach to modify physicochemical properties of encapsulated molecules. Such techniques, applied in topical formulations, fabrics modification for personal protection, or food packaging have proved to be more effective in increasing repellency time and also in reducing drug dermal absorption, improving safety profiles of these products. In this work, the main synthetic and natural insect repellents are described as well as their polymeric carrier systems and their potential applications.

Effective Insect Repellent Formulation in both Surfactantless and Classical Microemulsions with a Long‐Lasting Protection for Human Beings

The aim of this work is to develop a new generation of repellent products with a long-lasting protection based on a natural component, para-menthane-3,8-diol (PMD). The active is first rendered soluble in a surfactantless microemulsion (H(2)O/(i)PrOH/PMD) and then in classical microemulsions. The presence of self-associated nanostructures is detected by dynamic light scattering (DLS). A synergetic system of surfactants (Cremophor) RH40 and Texapon N70) is used. Additionally, 2-ethylhexane-1,3-diol and ethyl (-)-(S)-lactate are incorporated. The final product contains, as main components, 46% of H(2)O, 25% of (i)PrOH, 20% of non-H(2)O-soluble PMD, and only 4% of surfactants. Investigations of lasting protection on human volunteers are carried out using a cage test bioassay protocol and Aedes aegypti mosquitoes. A complete protection of 315 min is found on the test persons using the surfactantless microemulsion. An extension is observed with the final formulation to reach a mean of complete protection of 385 min. This study demonstrates that alternative formulations using a natural active instead of synthetic chemicals like N,N-diethyl-m-methylbenzamide (DEET) can be efficient for human protection against mosquitoes.

Analysis and mass spectrometric characterization of the insect repellent Bayrepel and its main metabolite Bayrepel-acid

Insect repellents such as N,N-diethyl- m-toluamide (DEET) which are used as protection against mosquitoes or ticks were detected in all wastewater and anthropogenically influenced surface waters analyzed. In Germany, the concentrations of DEET have constantly decreased since 1999, when DEET was substituted by Bayrepel (1-piperidinecarboxylic acid, 2-(2-hydroxyethyl), 1-methylpropyl ester; KBR 3023) in commercial insect repellent formulations. A sensitive quantitative method was developed in order to study the occurrence and fate of Bayrepel in the aquatic environment. It was thus determined that Bayrepel undergoes rapid primary aerobic biodegradation, yielding a more stable metabolite, Bayrepel-acid (1-piperidinecarboxylic acid, 1-methylpropyl ester, 2-acetic acid). In order to study the biodegradation and investigate the fate of this metabolite, Bayrepel-acid was synthesized and characterized. Various chromatographic and mass spectrometric techniques, such as gas chromatography–mass spectrometry (MS) after derivatization, liquid chromatography (LC)–electrospray ionization (ESI) MS and LC–ESI time-of-flight MS were applied.

Laboratory Evaluation of Controlled‐release Repellent Treated Pulp Fabric on Human Volunteers Against Mosquito Vectors

ABSTRACTThree controlled‐release personal‐use pulp fabric impregnated insect repellent formulations of 5% N, N‐diethyl‐3‐methylbenzamide (DEET), and 10% and 15% neem oils were evaluated in an environmental chamber on volunteers for their repellent efficacy against three mosquito species, Culex pipiens pallens, Aedes aegypti and Ochlerotatus togoi. The 5% DEET formulation showed significant repellency in pulp fabric (5 mm in width) against Culex pipiens pallens and Aedes aegypti (P < 0.05), providing an average repellency of 88.0%, 66.3%, and 46.8% of Cx. pipiens pallens, Ae. Aegypti and O. togoi bites, respectively, during the 6 hours of exposure period. Against night‐biting mosquitoes Cx. pipiens pallens, the DEET formulation provided mostly complete protection for at least 4 hours after the application. In pulp fabric of 10 mm in width, the 5% deet formulation showed significantly the highest repellency among the repellents against O. togoi (P<0.05), providing an average repellency of 52.3% during the 6 hours of exposure period. However, the pulp fabrics treated with 10% and 15% neem oil were less effective than 5% DEET against three mosquito species. This study demonstrated the potential of 5% DEET as pulp fabric repellent against both day‐ and night‐biting mosquitoes.

Assessment of Efficiency of Repellent Formulations with N,N‐diethyl‐m‐toluamide in Laboratory Conditions

The affinity of N,N-diethyl-m-toluamide) (DEET) for various polymers that are potential inert carriers (PEG, PVP, NaCMC, PAA) was studied. Mixtures of DEET and the polymers were prepared and analysed for DEET vapour release using head space analysis. Polyvinylpyrrolidone (PVP) showed the highest affinity for DEET. Several insect repellent formulations in the form of a hydrogel, an o/w cream and a stick were prepared with 5% w/w DEET and either 1% w/w or no PVP. The release of DEET from the formulations was investigated by Head Space gas-mass spectrometry at 32 degrees C. The degree of absorption of DEET through the skin was evaluated by applying these topical preparations to shaved rabbit skin and measuring DEET content in the blood samples by gas-mass spectrometry at various time intervals after application. Based on these results the pharmacokinetic parameters were determined. The minimum penetration of DEET through rabbit skin was obtained with a hydrogel containing PVP as a carrier. The biological efficiency of repellent formulations containing 5% DEET (w/w) was evaluated for repellency using the mosquito Aedes aegypti. The results demonstrated that the hydrogel formulation based on polyacrylic acid containing 5% DEET (w/w) supplemented with 1% PVP (w/w), could serve as a suitable vehicle for repellent preparations containing DEET.

Evaluation of commercial insect repellents on human skin against Aedes aegypti (Diptera: Culicidae).

An olfactometer was used to evaluate the efficacy of selected commercial insect repellent products against Aedes aegypti (L.). A comparison of 12 commercial repellent products was made on human skin. The products tested included 2 natural oil insect repellent formulations (Buzz Away and Green Ban) containing plant extracts, 2 proprietary products (Skin-So-Soft lotion and bath oil), and 8 commercial deet preparations in various concentrations and forms of spray, aerosol, stick, cream, and lotion. Behavioral responses and time to probe were determined in triplicate using 10 female mosquito challenges per replicate for each product. Generally, products with higher concentrations of deet were found to have longer repellence times. OFF spray and Muskol lotion offered the longest repellence times. However, there was no significant difference in time for mosquitoes to probe among the formulations. Skin-So-Soft lotion and bath oil were not as effective as deet in repelling Ae. aegypti. Natural oil insect repellent formulations offered essentially no repellency against Ae. aegypti. This is a simple and reproducible method to evaluate the efficacy of insect repellents and is recommended for preliminary screening of new insect repellents or formulations.

Reduced Transdermal Absorption of N,N-Diethyl-m-toluamide from a New Topical Insect Repellent Formulation

ABSTRACTExtensive absorption of the topical insect repellent N, N-diethyl-m-toluamide (DEET) causes systemic and local toxicities. This report describes the preparation and characterization of a new insect repellent formulation (FA), a PEG-polyacrylic acid polymer system, for its DEET release, in vitro skin permeation, and in vivo transdermal absorption properties; and for its relative repellency against Aedss aegypti mosquitoes. DEET release and skin permeation were studied in Franz diffusion cells. DEET transdermal absorption and relative repellency of FA were assessed in beagle dogs. A commercial DEET lotion (FB) and technical DEET (FC) were used as references. FA exhibited 19.5% and 61.7% decrease in DEET steady-state skin flux compared with FB and FC, respectively. At 15 mg DEET/kg, the absolute DEET transdermal bioavailability and Cmax were 13.4% and 154.3 ng/ml, respectively, for FA; and were 17.5% and 196.5 ng/ml, respectively, for FB. DEET half-lives (t1/2) for FA (2.52 hr) and FB (2.73 hr) were similar, while MRTfor FA (4.99 hr) was significantly greater (p < 0.05) than that for FB (4.38 hr). FA showed lower mosquito biting rates at 1, 2, 3, 4, 5, and 6 hr postdose at 0.5 mg DEET/cm2. FA exhibited reduced in vitro skin permeation and in vivo transdermal absorption of DEET as well as superior repellency compared with FB. The PEG-polyacrylic acid polymer system is of value in the formulation of DEET lotions.

Voltammetric Determination of the Insect Repellent Dipropyl Pyridine-2,5-dicarboxylate in Non-aqueous Solvents

The insect repellent di-propyl pyridine-2,5-dicarboxylate (MGK 326) may be reduced in aprotic acetonitrile at glassy carbon, platinum and hanging mercury drop (HMDE) electrodes to give an analytically ideal, reversible one-electron process with a reversible potential (E°′ value) of –1840 mV versus Ag/Ag+. In contrast, the reduction of MGK 326 in the protic solvent methanol and acetonitrile containing a molar excess of phenol occurs as a single two-electron chemically irreversible step. The addition of a proton source to acetonitrile can be observed to cause irreversibility in the reduction of MGK 326 with an accompanying positive shift in the reduction potential. Thus, in the presence of a proton source, the initially formed radical anion is protonated and further reduced at a potential less negative than the E°′ value. The reduction process in acetonitrile at a glassy carbon electrode was applied to the selective determination of MGK 326 in a commercial insect repellent formulation. Using differential-pulse voltammetry, a concentration of 41.4g l–1 with an RSD of 4.6% was obtained, compared with the concentration of 41.8 g l–1 stated by the manufacturer. The limits of detection (3ς) of MGK 326 in acetonitrile, using differential-pulse voltammetry, were 7.2 × 10–7M at an HMDE and 1.4 × 10–6M at a glassy carbon electrode. The limits of quantification (10ς) were 1.8 × 10–6 and 4.3 × 10–6M at an HMDE and a glassy carbon electrode, respectively.

Compatibility of Army Face Paint and Insect Repellent Formulation

The compatibility studies of a new controlled-release repellent formulation (NSN 6840-01-284-3982, insect repellent personal application) and a new camouflage face paint (NSN 6850-01-262-0635) indicated that the repellent did not interfere with the use of face paints when repellent was applied first, and the face paints did not reduce the effectiveness of the repellent against mosquitoes.