Acute Dermal Toxicity Research Articles

Evaluation of the Cutaneous Toxicity of the Aqueous Extract of the Aerial Parts of Mitracarpus scaber (Rubiaceae) in Rats (Rattus norvegicus Strain Wistar)

Mitracarpus scaber is a known plant in the Ivorian pharmacopoeia where it is used in various ways for the treatment of different diseases and ailments, including skin problems. The present study aims at evaluating the cutaneous toxicity of the aqueous extract of the aerial parts of M. scaber in the Wistar rat following exposure to a single dose or repeated doses. In the acute dermal toxicity experiment, a total of six (6) female rats were divided into two (2) groups, with three (3) rats per group. While a total of 32 male and female rats were divided into four (4) groups, each group consisted of eight (8) rats, four (4) males and four (4) females in the subacute dermal toxicity experiment. For the acute dermal toxicity study, rats in one group received a single application of the extract at the concentration of 2000 mg/ml on the first day of the experimental period. While the rats in the subacute study received topical application of the extract at the concentrations of 200, 400 and 800 mg/ml once a day for 28 days. The various applications were made to the dorsal shaved area of the skin. Throughout the respective fourteen (14) and twenty-eight (28) day study periods, all rats were monitored for any changes in physical appearance and behavior that might occur due to the toxic effects of the plant. No mortality or abnormal physical appearance was observed, and physiological and behavioral changes were not observed in all rats in either study. Body weight, kidney and liver weights, and hematology and biochemistry results did not show significant differences (p > 0.05) between all groups in the subacute study. Similarly, histopathological examinations of the liver, kidney and skin revealed no structural alterations. This study suggests that topical application of the aqueous extract of the aerial parts of M. scaber does not induce acute and subacute adverse effects on the skin or systemic toxicity in Wistar rats.

Toxicological Evaluation of Silver Nanoparticles Synthesized with Peel Extract of Stenocereus queretaroensis.

Silver nanoparticles (AgNPs) synthesized with plants are widely used in different industries, such as the medical, industrial, and food industries; however, their hazards and risks remain unclear. Here, we aimed to evaluate the toxicological effects of AgNPs in both in vitro and in vivo models. Previously, we developed and characterized green synthesized AgNPs based on Stenocereus queretaroensis (S. queretaroensis). The present study evaluates the toxicity of these AgNPs through cytotoxicity and mutagenicity tests in vitro, as well as genotoxicity tests, including the evaluation of acute oral, dermal, and inhalation toxicity, along with dermal and ocular irritation, in vivo, according to guidelines of The Organization for Economic Co-operation and Development (OECD). We evaluated cell cytotoxicity in L929 cells, and the half-maximal inhibitory concentration was 134.76 µg/mL. AgNPs did not cause genotoxic or mutagenic effects. Furthermore, in vivo oral, dermal, and acute inhalation toxicity results did not show any adverse effects or mortality in the test animals, and after the dermal and ocular irritation assessments, the in vivo models did not exhibit irritation or corrosion. Therefore, the results show that these previously synthesized S. queretaroensis AgNPs do not represent a risk at the tested concentrations; however, little is known about the effects that AgNPs induce on physiological systems or the possible risk following long-term exposure.

Evaluation of Wound Healing Activity of 80% Methanol Root Crude Extract and Solvent Fractions of Stephania abyssinica (Dill. & A. Rich.) Walp. (Menispermaceae) in Mice.

BackgroundThe root of Stephania abyssinica (Dill. and A. Rich.) Walp. (Menispermaceae) is traditionally used to treat wounds. Despite the fact that there have been in vitro studies and claims supporting wound healing, there has been no scientific data on the in vivo wound healing activities of the root of S. Abyssinica.ObjectiveThe aim of the study was to evaluate the wound healing activity of 80% methanol root extract and solvent fractions of S. Abyssinica in mice.MethodsThe roots of S. Abyssinica were air dried, ground and macerated by 80% methanol three times successively. The crude extract was fractionated by water, hexane and ethyl acetate separately. The acute dermal toxicity test was done by applying 2000 mg/kg of the 10% w/w crude extract. Wound healing activity of crude extract was evaluated on excision, incision and burn wound models, while the fractions were evaluated on excision wound model only.ResultsIn mice, an acute dermal toxicity test of 2000 mg/kg of the 10% w/w crude extract was found to be safe. The 10% w/w crude extract ointment (CEO) produced significant (p < 0.001) wound contraction from 4th to 16th post wounding days, and the 5% w/w CEO were significant (p < 0.01) wound contraction on 10th post wounding day as compared to simple ointment (SO) treated group on excision wound. On burn wound models, the CEO showed highly significant (p < 0.001) from the 6th post wounding days onwards. The tensile strength was increased significantly (p < 0.001) by the CEO treated mice as compared to the untreated group and SO group.ConclusionThe data obtained from this study showed 80% methanol crude extract, the aqueous and the 10% w/w ethyl acetate fraction possessed better wound healing activities, and decreased period of epithelialization.

Wound healing efficacy of novel ayurveda formulation- Pentabark Kashaya: In wistar rats using excision wound model- an in vivo study

BackgroundWound healing plays a major concern in the field of surgery as it requires uneventful healing. Management aims towards prevention of infection and to accelerate healing. Acharya Sushruta has given more emphasis on Vrana (wound) and its chikitsa (treatment). Many antiseptic agents which prevent infection are widely used but have no role in accelerating the healing process and are cytotoxic, deleterious to wound healing. In this regard an innovative polyherbomineral formulation Pentabark Kashaya (PK)was formulated to assess acute dermal toxicity and woundhealing activity. ObjectiveTo explore the wound healing efficacy of novel Ayurveda Formulation i.e Pentabark Kashaya in Wistar rats using the excision wound model. Materials and methodAcute dermal toxicity study was carried out on five female Wistar rats by following the OECD guideline 434 and signs of toxicity were assessed for the period of 14 days. Wound healing activitywas assessed on the excision wound model. 18 male Wistar rats were procured for the study and divided into three groups (n = 6 in each group). The test group was treated with application of PK, standard group with Povidone iodine solution 5% and control group with distilled water. The parameters assessed were epithelialization period, wound contraction rate, wound closure day and swab test for microbial load for the period of 21 days. Statistical analysis was done by using one way ANOVA and Tukeys HSD to assess changes in between three groups at each time point. ResultsNo signs of acute dermal toxicity were seen, which proved that PK is safe for application. Significant results were seen in the parameters of wound healing like period of epithelialization and wound closure day. Percentage of wound contraction rate was increased in test group when compared to other groups. Histopathology of skin showed marked changes in re-epithelialization, dermal fibroblast, dermal fibrocytes in test group when compared to control group. ConclusionPK is safe for application and it is effective in wound healing.Clinical Trial Registration No.: Not applicable.

Preclinical safety of tetrahydrocurcumin loaded lipidic nanoparticles incorporated into tacrolimus ointment: In vitro and in vivo evaluation

Preclinical safety and proof of concept studies for a topical ointment comprising of concentrated tetrahydrocurcumin loaded lipidic nanoparticles (THC-LNs) and tacrolimus ointment (TTO) is proposed in the present investigation. The skin irritation potential and acute dermal toxicity were performed in rats in compliance with the Organization for Economic Cooperation and Development (OECD) guidelines (402, 404 and 410) while the cytotoxic potential was performed in HaCaT cells. Finally, in vivo evaluation was performed in Imiquimod mice model of psoriasis. In primary skin irritation assessment, TTO formulation, marketed formulation (Tacroz® Forte), THC-LNs, and blank LNs were topically applied on intact skin sites in rats while another group served as a negative control group for 72 h. TTO did not induce any adverse reactions. Repeated 28 days dermal toxicity followed by biochemical and histopathological assessment showed negligible alternations and skin lesions. THC-LNs revealed negligible cytotoxic potential in HaCaT cells. TTO showed significantly high anti-psoriatic activity in comparison to marketed ointment. This was also confirmed via histopathological evaluation. Based on these findings, it can be ascertained that TTO showed minimal toxicity and has ample potential for further clinical analysis. The above studies affirm the potential of TTO as an alternative for psoriasis.

Acute and subchronic toxicity of multicomponent antiparasitic drugs Insaсar Total C Plus, Insaсar Total K Plus

The purpose of the research is to study acute oral toxicity in mice, and acute dermal and subchronic toxicity in rats of multicomponent antiparasitic Insacar Total C Plus (for dogs) and Insacar Total K Plus (for cats).Materials and methods. The toxicity of the drugs was studied in September-April 2020–2021 at the premises of the VNIIP – FSC VIEV Vivarium. To determine acute oral toxicity, 80 outbred mice weighing 20 g were used, of which 7 test and one control group were formed. The drugs were administered once in a 1 : 3 dilution with polyethylene glycol as a solution through an intragastric tube and an automatic controller. The control animals were intact. After a single administration, the physical condition of the test mice was monitored within 14 days; weight gain, expected clinical toxicity symptoms and possible death were assessed. Before and on days 1, 3, 7, 11 and 14 of the experiment, the test and control mice’s weight gain were evaluated. The toxicity parameters were calculated by the methods of Pershin, Miller and Taintner. In a subchronic experiment, the study drugs were tested on 80 outbred white rats divided into 6 test and 2 control groups. The rats’ coat was also shaved on the back. The solution was applied to the shaved skin area once a day for 7 days at doses of 1,000 mg/kg (0.1 mL/100 g), 500 mg/kg (0.05 mL/100 g) and 200 mg/kg (0.02 mL/100 g) of the animal weight. On day 8 of the experiment, 5 rats from each group were euthanized; their blood samples were taken, and the internal organs were examined. On day 21 of the experiment, the second part of the animals was euthanized to analyze the reversibility of potential pathoanatomical changes after prolonged repeated application of the drug. The results were processed statistically.Results and discussion.The half-lethal dose (LD 50) after oral administration of the drug for dogs to the mice was 2,475 by the Pershin method, and 2,500±388 mg/kg by the Miller and Taintner method. LD50 of the drug for cats when administered into the mice’s stomach was 2,713 by the Pershin method, and 2,650±403 mg/kg by the Miller and Taintner method (hazard class 3). LD 50 when applied to the rats’ skin was more than 10,000 mg/kg (hazard class 4). When applied once to the rats’ skin, the drugs had a slightly irritating effect. In subchronic experiment on the rats with daily drug application on their skin at doses of 1,000 mg/kg, 500 and 200 mg/kg, no negative effects on the general condition or death of the animals were observed during the entire study. Hematological and biochemical parameters of the test rats that were treated with the drug for dogs at a dose of 200 mg/kg, an increased content of lymphocytes up to 83.40% was observed on day 8 of the experiment, and up to 74.20 % in the control; and an increased glucose level up to 6.08±1.23 mmol/L, and up to 4.82±0.70 mmol/L in the control; LDH was up to 766.00±264.19 U/L, and up to 434.80±525.89 U/L in the control.

Assessment of Toxicity and Wound Healing Activity of Selaginella Bryopteris Extract

Aim The aim of the study was to assess the toxicity profile of Selaginella bryopteris extract and evaluate its wound healing activity. Methods In vitro wound healing activity of S. bryopteris extract (5% and 10%) was performed using Clonogenic and Scratch assays. The toxicity profile of S. bryopteris extract ointment was evaluated on animals using acute toxicity and dermal toxicity tests. In vivo wound healing activity of S. bryopteris extract ointment (5% and 10%) was used to determine tensile strength in the incision wound healing model. Results Results exhibited that the extract was safe up to 2000 mg/kg per oral dose and non-reactive while applied topically. In vitro results showed that S. bryopteris extract closed the wound gap created by 97.13% in 48 h. The clonogenic assay revealed that the surviving factor for HaCaT cells and MEF cells was 0.78 and 0.85 after treated with 10% concentrations of S. bryopteris. The tensile strength exhibited by S. bryopteris 5% and 10% groups was 395.4 g and 558.5 g in comparison to the control group. Conclusion Thus, S. bryopteris extract can be used as an alternative safe drug therapy against topical wounds.

Evaluation of Dermal Toxicity and Wound Healing Activity of Cnestis ferruginea Vahl ex DC.

Cnestisferruginea is a tropical plant, which is traditionally used in the treatment and management of various conditions including skin infections and wounds. The aim of this study was to investigate the dermal toxicity and wound healing potential of C. ferruginea. Ten millimeter full-thickness mucosal wounds were created on the dorsal midportion of the Sprague Dawley rats. Wounds were treated with 10, 5, and 2.5% w/w aqueous creams, prepared from the methanol extract of the root bark of C. ferruginea (CFM). The wound tissues were harvested on day 21 for histology studies. Compared with the untreated group, 10, 5, and 2.5% w/w CFM-treated wounds significantly reduced the wound size over the study period (P < 0.0001). Tissue histology revealed a healed wound with well-regenerated collagen and skin appendages with no pus cells. A skin irritation test was conducted on CFM, as well as the dermal toxicity of CFM was determined in the repeated dose and acute dermal toxicity bioassays. These tests revealed that CFM showed no toxic effect on the skin and showed that CFM was not a skin irritant. C. ferruginea exhibited wound healing activity, which gives credence to its folkloric use.

Toxicological Assessments of a Proprietary Blend of Punica granatum Fruit Rind and Theobroma cacao Seed Extracts: Acute, Subchronic, and Genetic Toxicity Studies.

LN18178 (Tesnor®) is a standardized, proprietary composition of aqueous ethanol extracts of Punica granatum fruit rind and Theobroma cacao seeds. The present study demonstrates a broad-spectrum toxicological evaluation of LN18178 utilizing in vitro and in vivo preclinical models following the Organization for Economic Cooperation and Development (OECD) guidelines for testing chemicals. Wistar rats did not show any clinical signs of toxicity and morbidity in acute oral and dermal toxicity tests with the median lethal dose (LD50) values of at least 5000 mg/kg and 2000 mg/kg body weight, respectively. LN18178 was nonirritating to the skin and eyes of the treated rabbits. In a ninety-day subchronic repeated oral dose toxicity study, the LN18178-treated Wistar rats did not show dose-related signs of toxicity on their body weight, food consumption, organ weights, hematology, and clinical chemistry parameters. The estimated no-observed-adverse-effect level (NOAEL) of LN18178 in male and female rats was 2500 mg/kg body weight. The observations from the bacterial reverse mutation test, in vitro chromosomal aberration assay, micronucleus assay in mouse bone marrow erythrocytes, and in vitro mouse lymphoma TK+/− gene mutation assay suggest that LN18178 is neither mutagenic nor clastogenic. In summary, the present study demonstrates that oral consumption of the herbal blend LN18178 does not show signs of toxicity; also it does not elicit genetic toxicity in the standard preclinical models.

Wound Healing Activity of 80% Methanolic Crude Extract and Solvent Fractions of the Leaves of Justicia schimperiana (Hochst. ex Nees) T. Anderson (Acanthaceae) in Mice.

IntroductionJusticia schimperiana has been used traditionally for the treatment of wound and skin burn, but there is no scientific evidence that supports the traditional claim.ObjectiveTo evaluate the wound healing activity of 80% methanol crude extract and solvent fractions of the leaves of Justicia schimperiana in mice.MethodsMice were used for wound healing study, while rats were used for acute dermal toxicity test. The 80% methanol crude extract and chloroform, ethyl acetate and aqueous fractions were formulated in ointments with 5% and 10% strength. Burn, excision and incision wound models were used to evaluate the effect of the crude extract, whereas the activity of the solvent fractions was evaluated using excision wound model. Parameters such as wound contraction, and period of epithelialization were studied in the excision and burn wound models, while tensile strength was measured in incision wound model.ResultsTreatment of wound with 80% methanol extract of Justicia schimperiana leaves using 5% (w/w) and 10% (w/w) ointment formulation induced significant (P<0.05) improvement in wound contraction rate, epithelialization time and skin breaking strength in excision, incision and burn wound model, respectively as compared to negative control. The chloroform, ethyl acetate and aqueous fractions with 5% (w/w) and 10% (w/w) ointment formulation showed significant (p<0.001) improvement in wound contraction and epithelialization time in excision wound model as compared to the negative control group.ConclusionThis study has demonstrated that the 80% methanol crude extract and solvent fractions of Justicia schimperiana leaves possess wound healing activity.

Evaluation of acute dermal toxicity of a topical anti-mastitis gel

This study was undertaken to evaluate the acute dermal toxicity of a topical anti-mastitis gel (Mastilep® gel; M/s Ayurvet Limited, India) in accordance with OECD 402 guidelines. Nine adults female Wistar rats, weighing 210-250 g, were used in the study. Following the topical application of the anti-mastitis gel, the animals were observed for the manifestation of toxic effects and mortality. Toxicity was evaluated on the basis of changes in body weight, histological appearances of heart, liver, kidney, and lungs, and blood biochemical parameters viz. AST, ALT, ALP and creatinine. Since no toxic effects or deaths were recorded until completion of the experiment, the anti-mastitis gel was found safe for dermal use.

An experimental study to evaluate acute dermal toxicity of Rasakriya in Wistar rats

Background – Rasakriya is a herbo-mineral preparation explained under the heading of Shashti upakrama by Acharya Sushruta in the management of Dushtavrana. Safety of drugs prior to application to see its efficacy is very important as Chronic Wound is more prone for infection.&#x0D; Objective – To evaluate Acute Dermal toxicity of Rasakriya on Female Wistar rats.&#x0D; Materials and Methods – The study was conducted as per the OECD guidelines 402. The study was conducted under two Headings i.e. Sighting study and Limit test study. In Sighting study the prepared Rasakriya at the dose of 2000 mg/kg body weight was applied on the depilated area and observed for the signs of Toxicity for 14 days, later limit test group animals were similarly treated and observed for 14 days. Observation was done for body weight changes, clinical signs of toxicity and mortality.&#x0D; Results – Dermal application of Rasakriya did not exhibit any signs toxicity with respect to Dermal, Circulatory, Respiratory, Central Nervous System and Behavioural pattern. There were no unscheduled deaths reported in animals during the study period, so, the animals were rehabilitated after the completion of the study.&#x0D; Conclusion – Rasakriya is safe for application as mortality and signs of toxicity were not observed in the study.&#x0D; Keywords – Rasakriya, Acute Dermal Toxicity, Sighting Study, Limit Test Study.

Evaluation of Safety and Efficacy of an Ayurvedic Ointment against Acute Burn Injury in Wistar Rats

Skin burn is a common health problem that needs a fast and accurate treatment; else, it can have a worse prognosis. The available treatment options pose limitations due to their adverse effects; thus there is an urgent need to find newer treatment options for burn wound healing that can provide a safer and faster treatment option. Ayurveda gives a plethora of medicinal plants and their formulations which have been used in the management of burn wound. The Ayurvedic ointment formulated in this experiment utilizes essential ayurvedic ingredients which are known for their burn wound healing potential. The current work includes the formulation of the Ayurvedic ointment, its standardization, toxicity and efficacy study. The Ayurvedic ointment was formulated by fusion method, and its physicochemical characterization ensures the purity of the compounds used for the formulation. The ointment formulated is well set under the safety parameters for the presence of heavy metals and also free from microbial and fungal contamination. It has obtained optimum spreadability and viscosity, making it desirable for application on wounds. In the acute dermal toxicity study, it has shown no adverse effect on the animals as there were no significant changes in the body weight and feed intake and water consumption, thus confirming it as a safe formulation. It has shown significant rate of wound healing and period of re-epithelization in the Wistar rat model. It can be a potential ointment for burn wound treatment, and in future, it can be considered for clinical studies to validate its safety and efficacy in humans.

Utility of the combination of hederagenin glucoside saponins and chromane hydrazone in the topical treatment of canine cutaneous leishmaniasis. An observational study.

Canine cutaneous leishmaniasis (CCL) is an emerging zoonotic infection endemic in several countries of the world. Due to variable response to therapy and frequency of relapses, a more effective, safer, and inexpensive treatment is needed. Recently, it was reported that the hederagenin glucoside saponins (SS) and chromane-derived hydrazone (TC2) combined in a 1:1 ratio has high potential in antileishmanial therapy since both compounds alter the survival of Leishmania and the ability to infect adjacent macrophage. Not only the skin permeation and the absorption of an ointment containing 2% TC2 and 2% SS (w/w) was determined in this work, but also the acute dermal toxicity in both in vitro and in vivo assays. Last, the effectiveness and safety of the topical therapy with 2% TC2-2% SS ointment was evaluated in an observational study in dogs with diagnosis of cutaneous leishmaniasis (CL). Both TC2 and SS diffused through pig ear skin and traces of TC2 (but not SS) were detected in the stratum corneum of mice at 6-24h. Neither TC2 nor SS was detected in plasma. The acute dermal toxicity was negative. Treatment with 2% TC2-2% SS ointment produced a complete long-term clinical cure in 56 dogs (24 females and 32 males) from the Orinoco and Amazonas regions in southeastern Colombia without adverse effects. All dogs have remained disease-free for the last 24months. In conclusion, these results support the use of this topical therapy as a safer and new first-line local treatment of CCL that could help limit the spread of CL from dogs to humans.

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.

STopTox: An in Silico Alternative to Animal Testing for Acute Systemic and Topical Toxicity.

Background:Modern chemical toxicology is facing a growing need to Reduce, Refine, and Replace animal tests (Russell 1959) for hazard identification. The most common type of animal assays for acute toxicity assessment of chemicals used as pesticides, pharmaceuticals, or in cosmetic products is known as a “6-pack” battery of tests, including three topical (skin sensitization, skin irritation and corrosion, and eye irritation and corrosion) and three systemic (acute oral toxicity, acute inhalation toxicity, and acute dermal toxicity) end points.Methods:We compiled, curated, and integrated, to the best of our knowledge, the largest publicly available data sets and developed an ensemble of quantitative structure–activity relationship (QSAR) models for all six end points. All models were validated according to the Organisation for Economic Co-operation and Development (OECD) QSAR principles, using data on compounds not included in the training sets.Results:In addition to high internal accuracy assessed by cross-validation, all models demonstrated an external correct classification rate ranging from 70% to 77%. We established a publicly accessible Systemic and Topical chemical Toxicity (STopTox) web portal (https://stoptox.mml.unc.edu/) integrating all developed models for 6-pack assays.Conclusions:We developed STopTox, a comprehensive collection of computational models that can be used as an alternative to in vivo 6-pack tests for predicting the toxicity hazard of small organic molecules. Models were established following the best practices for the development and validation of QSAR models. Scientists and regulators can use the STopTox portal to identify putative toxicants or nontoxicants in chemical libraries of interest. https://doi.org/10.1289/EHP9341

Secondary Amine Pendant β-Peptide Polymers Displaying Potent Antibacterial Activity and Promising Therapeutic Potential in Treating MRSA-Induced Wound Infections and Keratitis.

Interest in developing antibacterial polymers as synthetic mimics of host defense peptides (HPDs) has accelerated in recent years to combat antibiotic-resistant bacterial infections. Positively charged moieties are critical in defining the antibacterial activity and eukaryotic toxicity of HDP mimics. Most examples have utilized primary amines or guanidines as the source of positively charged moieties, inspired by the lysine and arginine residues in HDPs. Here, we explore the impact of amine group variation (primary, secondary, or tertiary amine) on the antibacterial performance of HDP-mimicking β-peptide polymers. Our studies show that a secondary ammonium is superior to either a primary ammonium or a tertiary ammonium as the cationic moiety in antibacterial β-peptide polymers. The optimal polymer, a homopolymer bearing secondary amino groups, displays potent antibacterial activity and the highest selectivity (low hemolysis and cytotoxicity). The optimal polymer displays potent activity against antibiotic-resistant bacteria and high therapeutic efficacy in treating MRSA-induced wound infections and keratitis as well as low acute dermal toxicity and low corneal epithelial cytotoxicity. This work suggests that secondary amines may be broadly useful in the design of antibacterial polymers.

The Wound-Healing Effect of Mango Peel Extract on Incision Wounds in a Murine Model.

Mangifera indica can generate up to 60% of polluting by-products, including peels. However, it has been shown that flavonoids and mangiferin are mainly responsible for the antioxidant, anti-inflammatory, and antibacterial activities closely related to the wound-healing process. The chemical composition of MEMI (methanolic extract of M. indica) was analyzed by HPLC-DAD, as well as concentrations of total phenol (TPC) and flavonoids (TFC) and antioxidant activity (SA50). Wound-healing efficacy was determined by measurements of wound contraction, histological analysis, and tensiometric method; moreover, anti-inflammatory, antibacterial, and acute dermal toxicity (OECD 402) were also evaluated. Phenol, resorcinol, conjugated resorcinol, and mangiferin were detected. TPC, TFC, and SA50 were 136 mg GAE/g, 101.66 mg QE/g, and 36.33 µg/mL, respectively. Tensile strength and wound contraction closure did not show significant differences between MEMI and dexpanthenol groups. Histological analysis (after 14 days) shows a similar architecture between MEMI treatment and normal skin. MEMI exhibits a reduction in edema. Staphylococcus epidermidis had an MIC of 2 mg/mL, while Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli reached 4 mg/mL. The MEMI showed no signs of toxicity. Therefore, this study demonstrates multiple targets that flavonoids and mangiferin of MEMI may present during the healing process.

Evaluation of Comparative Dermal Toxicity and Efficacy of Aargwadhadi Oil and Aargwadhadi Ointment

Introduction: Skin diseases are among the most common of all health illness in recent years, In Ayurveda, management of skin diseases includes internal and external administration. External administration includes various topical applications However, herbal medicines are not completely safe from adverse effects and develop irritation, rashes, redness and burning sensation on the skin as observed in recent researches.“Hence there is a requirement of a safe drug which should be economical &amp; affordable for all. Hence present study is undertaken to study dermal toxicity profile Aargwadhadi oil and Aargwadhadi ointment in an experimental animal and make available safe and efficient drug to the human being.&#x0D; Aim and Objective: Pharmaceutical development, standardization and evaluation of acute, sub-acute dermal toxicity and efficacy of a Aargwadhadi oil and Aargwadhadi ointment and compare efficacy and safety of Aargwadhadi oil and Aargwadhadi ointment.&#x0D; Materials and Methods: Aargwadhadioil and Aargwadhadi Ointment will be prepared as per classical reference and it will be converted into ointment form. Analytical study for standardization of Aargwadhadi oil and Aargwadhadi ointment will be done. Evaluation of Acute and sub-acute dermal toxicity study in experimental animals of both dosage forms as well, efficacy study of Aargwadhadi oil and Aargwadhadi ointment on animal model of vitiligo will be done.&#x0D; Observations and Results: Observation will be done on the basis of assessment criteria evaluation of control group and experimental group will be noted. Results will be drawn on the basis of observations and applying suitable tests. It will be noted and presented in form of table, charts, graphs etc.&#x0D; Conclusion: Conclusion of the study will be drawn accordingly from the recorded observations, analysis of data.

Antimicrobial Polypeptides Capable of Membrane Translocation for Treatment of MRSA Wound Infection In Vivo.

Multidrug resistant infections are plaguing the healthcare sector over the past few decades with limited treatment options. To overcome this problem, the authors synthesize a series of novel guanidinium-functionalized polypeptides. Specifically, poly(l-lysine) (PLL) with different lengths is first synthesized by ring-opening polymerization of Nε -benzyloxycarbonyl-l-lysine-N-carboxyanhydride (Lys(Z)-NCA) followed by functionalization with a guanidinium-functional group to obtain guanidinium-functionalized PLL (PLL-Gua). To study the effect of hydrophobicity on antimicrobial activity, relatively more hydrophobic leucine-NCA monomer or hydrophobic vitamin E moiety is introduced to PLL-Gua. These polypeptides are characterized for antimicrobial activity against a panel of microbes including multidrug-resistant bacteria, and hemolytic activity. Among all the polypeptides, PLL22 -Gua is most effective against bacteria and yeast. Particularly, excellent bactericidal activity is observed against Staphylococcus aureus and MRSA. PLL22 -Gua kills bacteria mainly by membrane translocation. In addition, PLL22 -Gua kills MRSA with low resistance frequency (<3.3 × 10-8 ). In an MRSA-caused wound infection mouse model, two-day treatment (twice daily) with 10, 20, or 40mg per kg of PLL22 -Gua shows up to 99.5% bacterial removal. Moreover, no acute dermal toxicity is observed even at a dose of 200mg per kg. These promising results show the excellent potential of PLL22 -Gua as an antimicrobial agent against multidrug-resistant infection in vivo.