Skin Regenerative Potential of Cupuaçu Seed Extract (Theobroma grandiflorum), a Native Fruit from the Amazon: Development of a Topical Formulation Based on Chitosan-Coated Nanocapsules

Scarless skin regeneration is a challenge in regenerative medicine. Herein, we explore the regenerative potential of a Cupuaçu seed extract (Theobroma grandiflorum) to develop an innovative skin regeneration formulation based on chitosan-coated nanocapsules. Cupuaçu seed extract significantly stimulated cell proliferation and migration. A reparative gene expression profile could be verified following extract treatment, which included high levels of MKI67, a cellular proliferation marker, and extracellular matrix genes, such as ELN and HAS2, which code for elastin and hyaluronic acid synthase 2. Formulations with Cupuaçu seed extract successfully entrapped into nanocapsules (EE% > 94%) were developed. Uncoated or coated nanocapsules with low-molecular-weight chitosan presented unimodal size distribution with hydrodynamic diameters of 278.3 ± 5.0 nm (PDI = 0.18 ± 0.02) and 337.2 ± 2.1 nm (PDI = 0.27 ± 0.01), respectively. Both nanosystems were physically stable for at least 120 days and showed to be non-irritating to reconstructed human epidermis. Chitosan coating promoted active penetration into undamaged skin areas, which were still covered by the stratum corneum. In conclusion, the present study demonstrated for the first time the biotechnological potential of the frequently discarded Cupuaçu seed as a valuable pharmaceutical ingredient to be used in regenerative skin products.

STATISTICAL OPTIMIZATION AND EVALUATION OF ETHOSOMAL MICONAZOLE NITRATE SUSPENSION

Objective: The objectives of the present study were to optimize and evaluate the ethosomal suspension of miconazole nitrate for the treatment of local and systemic fungal infections. Methods: Miconazole topical formulation is prepared for better patient compliance and to reduce the dose of a drug. Miconazole nitrate ethosomes were prepared by the cold method using factorial designing with Ethanol(X1), IPA(Isopropyl alcohol)(X2), and Lecithin(X3) as Independent variables and % EE(Entrapment efficiency)(Y1) and % DR(drug release at 8th h)(Y2) was selected as responses. Results: The results obtained in the design showed that there was no significant interaction among factors. The lecithin concentration had a positive response on % EE, while ethanol concentration and IPA had a positive effect. For % DR, Ethanol, and IPA showed a positive effect and Lecithin had a negative response. The formulation EM22 (3 ml X1,3 ml X2 and 300 mg of X3) characterized by high % EE(77.3 %) and optimum % DR(94.2%) and formulation EM6 (2 ml X1,2 ml X2 and 100 mg of X3) characterized by high % DR(97.32 %) and optimum % EE (74.8 %). EM22 was incorporated in the gel as it is showing more entrapment efficiency and compared with the marketed product for drug release. Conclusion: From the result, it was concluded that formulated ethosomal suspension and optimized gel have more drug release than marketed formulation so that formulated suspension can be used for the preparation of antifungal gels, creams, ointments for sustained release.

Anti-inflammatory activity of the topical formulation of Drymoglossum piloselloides (L) Presl. extract on mice

Background: Chronic inflammation of the joints that occur in the condition of gout or osteoarthritis and rheumatoid arthritis often causes repeated inflammation which requires patients to take a long-term pain medication, leading to serious side effects. Alternative treatment especially from herbal ingredients in a topical form is needed. Objective: This study aims to evaluate the anti-inflammatory activity of the leaves extract of Drymoglossum piloselloides (L) Presl. in mice to prove their potential as an anti-inflammatory agent. Methods: Mice were divided into four groups (n=7), namely positive control (sodium diclofenac emulgel), negative control (placebo), P1 (emulgel extract 2.5%), and P2 (emulgel extract 5%). The anti-inflammatory activity test was carried out on mice with carrageenan-induced paw edema by measuring the relative changes in the volume of inflammation at 0 and 3 hours after treatment. Data were analyzed using the Kruskal-Wallis and Mann-Whitney tests with a confidence level of 95%. Results: The emulgel contained flavonoids, triterpenoids, steroids, tannins, and quinones. The anti-inflammatory test showed a significant inhibition of inflammation (p <0.05) at concentrations of 2.5% and 5%. This anti-inflammatory activity could be influenced by the phytochemical compounds contained in the emulgel. Conclusion:Drymoglossum piloselloides (L) Presl. emulgel at concentrations of 2.5% and 5% had an anti-inflammatory activity on mice with carrageenan-induced paw edema. Keywords: inflammation, Drymoglossum piloselloides (L) Presl., emulgel

Pramoxine containing topical formulation of eberconazole in the management of dermatophytosis in India: a consensus statement

<p>Dermatophytosis, a superficial fungal infection has attained significant extents among Indian population. Its clinical presentation is diverse, often in terms of morphology, severity type and involvement of all age groups. Management of dermatophytosis has become an important public health issue in India. Cases of steroid modified dermatophytosis are being encountered frequently, mostly caused due to the inadvertent use of steroid in combination with topical antifungal agents. This combination is available over the counter and is often used for the management of inflammation and pruritis associated with the disease. Current treatment recommendations must be reviewed as per the current clinical scenario of the disease. Thus, a topical formulation of an anti-itch agent like pramoxine and antifungal agent with an anti-inflammatory property like eberconazole holds a promising treatment approach for dermatophytosis. This article focuses on the challenges encountered in the management of dermatophytosis and strategies for optimizing treatment for better patient outcomes. An expert’s panel discussion was conducted involving fifteen dermatologists all over India, during which modified Delphi method was executed for a set of nine statements. Agreement of more than 75% was set to reach the consensus. This consensus document was developed to review the available evidence and make recommendation based on the expert group’s opinion for the use of pramoxine containing topical formulation of eberconazole, as it provides the benefit of having an anti-inflammatory and anti-pruritic activity in a single formulation, where pramoxine can be utilised as an excipient to combat pruritis associated with dermatophytosis.</p><p><strong> </strong></p>

Development and Optimization of a Topical Formulation with Castanea sativa Shells Extract Based on the Concept “Quality by Design”

The proposed study aims to develop and optimize a topical formulation with Castanea sativa shells extract considering the concept of Quality by Design, focusing on a planned development that consider the vulnerabilities of the entire process through risk analysis tools and design of experiments (DoE). A Box–Behnken design with three factors and three levels was used as a statistical tool for the execution of the DoE and the analysis of the response surface methodology responses. The independent variables studied were the quantity of sodium lauryl sulfate (%) (X1), beeswax (%) (X2) and macadamia oil (%) (X3); the dependent variables were pH (Y1), viscosity (Y2) and adhesiveness (Y3). According to the mathematical model, the optimal formulation contains 0.93% of sodium lauryl sulfate, 5.00% of beeswax and 10.00% of macadamia oil. The optimal formulation with the extract was prepared and characterized over the time, regarding organoleptic and technological characteristics, allowing conclusions to be reached regarding its stability. The formulation presented a pleasant odor and was light brown in color, it also demonstrated pseudoplastic-thixotropic behavior and a small reduction in the formulation consistency after 30 days of storage. This study demonstrated the efficiency of the Quality by Design methodology to understand the product variability, supporting that this approach favors a better understanding of the whole process and enables to design a robust development stage, reducing costs and generating high-quality products.

Synthesis of rutin derivatives to enhance lipid solubility and development of topical formulation with a validated analytical method

Background: Rutin is available on the market as a topical formulation for the treatment of several conditions, such as internal bleeding, hemorrhoids, and varicose veins. However, these gels have low solubility and limited bioavailability due to their decreased lipid solubility. Objective: In this study, we aimed to synthesize potentially novel lipophilic rutin prodrugs. The suggested library of these rutin prodrugs includes changing the solubility profile to facilitate rutin transport across biological barriers, thereby improving drug delivery through topical application. Methods: Six rutin derivatives were synthesized based on the ester prodrug strategy. The synthesized compounds were formulated as topical ointments, and their permeability via Franz diffusion was measured. An ultraviolet (UV) analytical method was developed in our laboratories to quantify rutin derivatives both as raw materials and in final dosage forms. The analytical method was then validated. Result: The results of Franz diffusion analyses showed that transdermal permeability increased by 10_Fo.jpgl height=""d for decaacetylated rutin compared to the other esterified rutins. A simple analytical method for the analysis of the formulated rutin ester was developed and validated. Moreover, the formulated ointment of decaacetylated rutin in our research laboratory was found to be stable under stability accelerated conditions. Synthesis of potentially more lipophilic compounds would yield novel rutin prodrugs suitable for topical formulation. Conclusion: This project provides a synthetic approach for many similar natural products. The research idea and strategy followed in this research project could be adapted by pharmaceutical and herbal establishments.

Development and In Vitro/In Vivo Evaluation of pH-Sensitive Polymeric Nanoparticles Loaded Hydrogel for the Management of Psoriasis

Methotrexate (MTX), the gold standard against psoriasis, poses severe problems when administered systemically viz increased toxicity, poor solubility and adverse reactions. Hence, a topical formulation of MTX for the management of psoriasis can be an effective approach. The present study aimed to develop an MTX based nanoparticle-loaded chitosan hydrogel for evaluating its potential efficacy in an imiquimod-induced psoriatic mice model. MTX-NPs loaded hydrogel was prepared and optimized using the o/w emulsion solvent evaporation method. Particle size, zeta potential, entrapment efficiency, in vitro drug release, ex vivo permeation, skin irritation and deposition studies were performed. Psoriatic Area and Severity Index (PASI) score/histopathological examinations were conducted to check the antipsoriatic potential of MTX-NPs loaded hydrogel using an imiquimod (IMQ)-induced psoriatic model. Optimized MTX-NPs showed a particle size of 256.4 ± 2.17 nm and encapsulation efficiency of 86 ± 0.03%. MTX-NPs loaded hydrogel displayed a 73 ± 1.21% sustained drug release in 48 h. Ex vivo permeation study showed only 19.95 ± 1.04 µg/cm2 of drug permeated though skin in 24 h, while epidermis retained 81.33% of the drug. A significant decrease in PASI score with improvement to normalcy of mice skin was observed. The developed MTX-NPs hydrogel displayed negligible signs of mild hyperkeratosis and parakeratosis, while histopathological studies showed healing signs of mice skin. So, the MTX-NPs loaded hydrogel can be a promising delivery system against psoriasis.

Nanoliposomal Topical Formulation for Increasing Safety and Combating Microbial Drug Resistance in Leprosy

Nanoliposomes were prepared using solvent injection method and topical spray using simple dispersion method. The particle size and % Entrapment Efficiency were found 18.01 ± 0.21 nm and 87.71 ± 0.12% respectively. TEM studies showed that the particles were in spherical shape. Drying time, volume per spray, area of film and dose uniformity were found to be 280 ± 0.002 sec, 0.16± 0.021 ml, 155.57 ± 0.012 cm2 and 0.15± 0.0012 ml respectively which showed good spraying conditions on the affected area. Stability study shows that dapsone and chaulmoogra oil loaded nanoliposomal topical spray was stable at accelerated condition up to 1 month. The present investigation provides a safe approach by improving the outer membrane permeability to combat microbial drug resistance and increasing safety in leprosy treatment.

Theoretical and Experimental Study of New Dihydroorotate Dehydrogenase and Tryparedoxin Peroxidase Inhibitors: One More Step in the Study of Leishmaniasis Infection

In this study, the viability of new dihydroorotate dehydrogenase and tryparedoxin peroxidase inhibitors is reported. In vitro antileishmanial activity was evaluated using a Leishmania (V) panamensis strain, and the cytotoxicity of the compounds was assessed using U-937 cells. The in vivo therapeutic response was evaluated in golden hamsters (Mesocricetus auratus) experimentally infected with L. (V) panamensis and treated with a 1% topical formulation of compounds 4a–f. On the other hand, in silico studies considering the synthesized compounds were also carried out. All of the compounds showed promising in vitro activity, with mean EC50 effective concentration values ​​ranging from 3.8 µM to 19.3 µM. Likewise, treatment with compounds 4a–f produced improvement in most of the hamsters and cured some; in particular, those treated with compounds 4b, 4c, 4d, and 4f reacted the best. Molecular dynamics (MD) simulations, computational docking, and MM/GBSA studies indicate the promising bioavailability and absorption characteristics of the studied compounds, which are expected to be orally active. In addition, the studied 2-arylquinolines are absorbable at the blood–brain barrier, but not in the gastrointestinal tract. Finally, ADMET properties suggest that these molecules can be safely used as leishmaniasis inhibitors.

Role of topical nadifloxacin as an empirical treatment in patients with skin and soft-tissue infections in India: A review and consensus

Dermatologists often come across cases of skin and soft-tissue infections (SSTIs) which have diverse clinical presentations. Various local, systemic, and environmental risk factors predispose an individual to develop SSTIs. Topical antimicrobial agents are frequently used in superficial uncomplicated SSTIs, whereas systemic therapy is generally reserved for use in severe cases. However, emergence of resistance to these agents is becoming a common problem in clinical practice. This necessitates the use of other classes of antimicrobials for the effective treatment of SSTIs. Nadifloxacin, a potential drug belonging to the fluoroquinolone group, has various advantages such as binding to bacterial DNA gyrase and topoisomerase IV enzymes, inhibition of nor-A efflux pump, survival in acidic pH, anti-MRSA activity, and biofilms penetration. It has also shown least development of resistance since its introduction. Although its topical formulation has shown superior efficacy as an anti-acne agent, there are no specific guidelines for its appropriate use in SSTIs. Hence, a panel of experts was formed, under whose guidance an extensive literature search was performed in MEDLINE, Cochrane Library, and Science Direct databases. Using the modified Delphi technique, the available evidence was reviewed and corresponding recommendations were given for the use of topical Nadifloxacin as an empirical treatment in SSTIs.