Dermal Application Research Articles

Studies on acute dermal toxicity and dermal absorption of a nanoform zinc oxide (ZnO; NM-111) in rats.

Studies on acute dermal toxicity and dermal absorption of a nanoform zinc oxide (ZnO; NM-111) in rats.

Co-delivery of Azithromycin and nisin through liposomes for skin infection to reduce antimicrobial drug resistance.

Co-delivery of Azithromycin and nisin through liposomes for skin infection to reduce antimicrobial drug resistance.

ACUTE AND SUBACUTE TOXICITY OF SPRAY BASED ON CHLORTETRACYCLINE HYDROCHLORIDE

Aerosolized products based on tetracycline antibiotics are used in veterinary medicine to treat wounds, skin irritations, eczema, as well as hoof rot, skin diseases caused by microorganisms susceptible to tetracycline antibiotics. The study to determine the acute dermal toxicity of the spray was conducted in accordance with the requirements of OECD No. 402 (Acute Dermal Toxicity: Fixed Dose Procedure (October 9, 2017). For the experiment, healthy, young animals with intact skin, body weight 200-220 g were used. After application of the drug, the laboratory animals were monitored for 14 days. The following indicators were taken into account: appearance, behavior, coat condition, application site, visible mucous membranes, attitude to feed, rhythm, respiratory rate, time of onset and nature of intoxication, its severity and course. The study of dermal toxicity of the drug during prolonged use was performed in accordance with OECD No. 410 (Repeated Dose Dermal Toxicity: 21/28-day Study). For the experiment, healthy, young animals with intact skin, body weight 200-220 g were used. The day before the application of the test product, hair was removed from the dorsal surface (at least 10% of the total body surface area). Repeated hair removal was performed weekly. The study product was applied as evenly as possible to the prepared dorsal skin surface (i.e., at least 10% of the total body surface area). The study product was kept in contact with the skin with a porous gauze bandage and non-irritating tape, daily for 6 hours. The drug was applied to the skin daily for 28 days. At the end of the exposure period, the test product was removed, where possible, using water or a suitable solvent. For this purpose, 4 groups of animals were formed on the principle of analogs, 6 rats in each group. Water was applied to the previously prepared skin area of the control group. Animals of the first experimental group were treated with Cyclo Spray at a therapeutic dose of 0.4 ml per animal, animals of the second experimental group - 5 times the therapeutic dose - 2.0 ml per animal, and animals of the third experimental group - 10 times the therapeutic dose - 4.0 ml per animal. The next day after the end of the drug application, laboratory animals under light ether anesthesia were decapitated and blood samples were taken for further research in the laboratory of clinical and biological research of the State Research Institute of Veterinary Drugs and Feed Additives, while determining the coefficients of organ mass of white rats compared to the control group. The studies established that a single dermal application of the aerosol did not cause animal death, toxicity, or redness at the site of application, so according to the GHS, the test product belongs to category 5 (class 5, not classified). Prolonged topical application of the drug in high doses caused a decrease in protein synthesizing function of the liver, impaired renal function (decreased levels of urea and creatinine in the blood of animals) and liver (increased levels of ALT and ALP in the blood of animals).

Topical Application of Melatonin in a Grapeseed Oil-based Microemulsion Accelerated Wound Healing in Rat Models

Objective: Melatonin has been associated with accelerated tissue regeneration and grapeseed oil has abundant unsaturated fatty acids, particularly linoleic acid that makes it a strong antioxidant, having the potential to promote wound healing by enhancing the presence of free radicals at the wound site. The study is aimed to evaluate the potential of a microemulsion gel using grapeseed oil as the organic phase and melatonin encapsulated in the vesicles to exhibit synergistic wound healing in Swiss albino rats. Materials and Method: Microemulsion containing grapeseed oil encapsulating melatonin was developed using the water-titration method. The surfactant and co-surfactant ratio (Smix) were fixed at 1:1. A pseudo-ternary diagram was used to determine the microemulsion zone and the developed microemulsion was further incorporated in carbopol 934P gel. The formulations were evaluated for their physicochemical properties and cytotoxicity assay. The optimized formulation was topically applied to cutaneous wounds of Swiss albino rat models. 30 Swiss albino rats were divided into five groups of 6 animals each: (i) Negative control group, (ii) Standard marketed formulation treated group, (iii) Optimized microemulsion containing Grapeseed oil and melatonin treated group, (iv) Grapeseed oil treated group and (v) Melatonin treated group. All the rats in each group were topically applied with the desired formulations daily for up to 14 days. Results: The treatment with a formulation comprising 10.18% Grapeseed oil, 24.88% water, and 64.94% Smix exhibited the highest entrapment efficiency of 86.65 ± 1.88% with an enhanced in vitro drug release of up to 83.02 ± 1.09%, also demonstrating first-order release kinetics. Furthermore, it did not inhibit L929 mouse fibroblast cell proliferation up to 500 μg/mL and promoted wound closure prior to other groups. Additionally, increased tissue maturation with higher collagen deposition was mostly seen by day 7. Thus demonstrating it is suitable for dermal application and sustained release of melatonin. The in vivo wound healing study and histological investigations on rat models demonstrated comparable results as observed in the marketed formulation of melatonin. Conclusion: The results showed that GSO oil based microemulsion encapsulating MEL could be a promising wound treatment option to exhibit accelerated wound healing effects.

Novel silver(I) complexes with fenamates: Insights into synthesis, spectral characterization, and bioactivity.

Novel silver(I) complexes with fenamates: Insights into synthesis, spectral characterization, and bioactivity.

Utilizing response surface methodology for optimizing the synthesis of quercetin-loaded niosome by ethanol injection method

Abstract Recent studies have delved into the emerging realm of lipid-based nanomaterials (LNPs), with a specific focus on formulations for dermal applications. Niosomes, with their diminutive size and controlled release capacity, are explored as promising carriers for dermal delivery systems. Quercetin is well known as a potent antioxidant recognized for its skin benefits but challenged by limited solubility. To overcome this hurdle, the study introduces the integration of the ethanol injection method accompanied by response surface methodology (RSM)-central composite design (CCD) to optimize quercetin-loaded niosomes. The approach streamlines the formulation design process, providing an efficient and systematic approach for developing optimal cosmetic formulas with reduced experimentation. The results highlight the critical, independent factors, such as the cholesterol content (ratio of 1.7589, equivalent to 204.03 mg) and surfactant content (ratio of 1.8375, equivalent to 1687.10 mg), with tween 60 chosen as the surfactant. Under the optimal conditions, the synthesized niosomes exhibit an actual efficiency of 50.08% ± 0.31% and an average size of 47.0 ± 2.9 nm. Notably, the model demonstrates the precise predictive capability of the RSM-CCD method in optimizing the investigated parameters, offering valuable insights for future studies and applications in LNPs’ formation towards dermal formulations.

Glycerosomes: Versatile Carriers for Multi-Route Drug Delivery Systems.

Glycerosomes signify a groundbreaking advancement in drug delivery technology. Comprising glycerol, phospholipids, and water, glycerosomes offer superior drug stability, penetration, entrapment efficiency, fluidity, and viscosity compared with conventional liposomes. Their formation process eliminates the need for specific transition temperatures, streamlining production. Glycerol's plasticizing properties enhance vesicle elasticity and flexibility, enabling enhanced skin penetration. These vesicles demonstrate immense promise across a range of drug delivery pathways. In dermal and transdermal applications, glycerosomes augment drug permeation by moisturizing the stratum corneum and improving membrane fluidity. For oral delivery, they shield drugs from the harsh gastrointestinal environment and boost intestinal absorption. Pulmonary delivery benefits from glycerosomes' capacity to stabilize and disperse aerosolized vesicles, facilitating deep penetration into lung tissues. Ophthalmic applications profit from increased corneal penetration and extended retention. Intranasal use of glycerosomes enhances mucosal penetration and enables direct drug delivery to the central nervous system by circumventing the blood-brain barrier. Ongoing advancements in glycerosome technology concentrate on integrating diverse functional ingredients like essential oils, β-sitosterol, sodium hyaluronate, and trimethyl chitosan to develop specialized formulations. These variants include STO-glycerosomes, S-glycerosomes, PO-S-glycerosomes, HY-glycerosomes, TMC-glycerosomes, glycethosomes, and glycerospanlastics, all offering enhanced stability, permeability, and therapeutic efficacy. This review delves into the mechanisms of drug transport within glycerosomes, their applications in various delivery routes, and the latest technological developments, highlighting their substantial potential as versatile carriers in contemporary drug delivery systems.

The Effects of Encapsulating Bioactive Irish Honey into Pluronic-Based Thermoresponsive Hydrogels and Potential Application in Soft Tissue Regeneration.

Honey has been recognised for centuries for its potential therapeutic properties, and its application in wound healing has gained attention due to its antimicrobial, anti-inflammatory, and regenerative properties. With the rapid increase in multidrug resistance, there is a need for new or alternative approaches to traditional antibiotics. This paper focuses on the physicochemical changes that occur when formulating honey into Pluronic F127 hydrogels. The manual incorporation of honey, irrespective of quality type, presented the amelioration of Pluronic's capacity to undergo sol-gel transitions, as investigated by parallel plate rheology. This novel finding was attributed to the formation of fractal aggregates via the hydrogen-bonding-induced irreversible aggregation of honey-PF127 micelles, which subsequently dominate the entire hydrogel system to form a gel. The hydrogen bonding of micelles was identified through Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR), Differential Scanning Calorimetry (DSC), and Dynamic Light Scattering (DLS). This is the first known study to provide physicochemical insight into the effects that honey incorporation has on the thermogelation capacity of Pluronic F127 hydrogels for downstream dermal wound applications.

The flavouring agent, 2-octenoic acid kills Galleria mellonella (Lepidoptera: Pyralidae) by affecting their immunocompetent cells and cuticular FFA profiles.

The flavouring agent, 2-octenoic acid kills Galleria mellonella (Lepidoptera: Pyralidae) by affecting their immunocompetent cells and cuticular FFA profiles.

Infection by Mycobacterium abscessus as a Complication of Calcium Hydroxyapatite Injection: A Case Report and Literature Review

Non-surgical aesthetic procedures for managing skin aging have seen increased demand in recent years, among which are injectable collagen bio-stimulators such as calcium hydroxyapatite. These procedures aim at preventing aging and improving skin laxity. Some complications, such as the formation of nodules, hypersensitivity reactions, and granuloma formation, have been reported. In this article, we present a literature review on Mycobacterium abscessus infection following subdermal injection of calcium hydroxyapatite in a 56-year-old healthy woman who developed nodules on the forehead and malar region one month after the application. A culture of a skin biopsy fragment revealed the presence of Mycobacterium abscessus resistant mycobacteriosis, with the patient treated with clarithromycin, amikacin, and tigecycline for 30 days in an inpatient setting. After discharge, treatment continued with oral clarithromycin and doxycycline for 6 months, resulting in clinical cure. There are few reports in the literature of atypical mycobacteriosis following dermal application of bio-stimulators.

Stimuli-Responsive Self-Healing Ionic Gels: A Promising Approach for Dermal and Tissue Engineering Applications.

The rapid increase in the number of stimuli-responsive polymers, also known as smart polymers, has significantly advanced their applications in various fields. These polymers can respond to multiple stimuli, such as temperature, pH, solvent, ionic strength, light, and electrical and magnetic fields, making them highly valuable in both the academic and industrial sectors. Recent studies have focused on developing hydrogels with self-healing properties that can autonomously recover their structural integrity and mechanical properties after damage. These hydrogels, formed through dynamic covalent reactions, exhibit superior biocompatibility, mechanical strength, and responsiveness to stimuli, particularly pH changes. However, conventional hydrogels are limited by their weak and brittle nature. To address this, ionizable moieties within polyelectrolytes can be tuned to create ionically cross-linked hydrogels, leveraging natural polymers such as alginate, chitosan, hyaluronic acid, and cellulose. The integration of ionic liquids into these hydrogels enhances their mechanical properties and conductivity, positioning them as significant self-healing agents. This review focuses on the emerging field of stimuli-responsive ionic-based hydrogels and explores their potential in dermal applications and tissue engineering.

Skin penetration enhancers: Mechanistic understanding and their selection for formulation and design.

The skin functions as a formidable barrier, particularly the stratum corneum, effectively restricting the penetration of most substances, including therapeutic agents. To circumvent this barrier, skin penetration enhancers (SPEs) are frequently employed to transiently increase skin permeability, facilitating drug absorption without causing irritation or damage. Despite advancements in dermal formulation development, a deeper understanding of the fundamental science underpinning drug delivery via SPEs remains essential. This review delivers a critical update on conventional SPEs, exploring their mechanisms in promoting drug permeation across the skin. In addition to offering an overview of percutaneous drug delivery, we examine the prevailing theories on how SPEs enhance drug transport. Furthermore, we address the intricate interplay between SPEs, drugs and the skin, providing valuable insights into how the molecular properties and permeation behaviours of SPEs influence their efficacy. This comprehensive review aims to support the ongoing development of optimised drug delivery systems for dermal applications by elucidating the complexities and challenges involved in using SPEs effectively.

Synthetically programmed antioxidant delivery by a domesticated skin commensal.

Synthetically programmed antioxidant delivery by a domesticated skin commensal.

The safety and anti-adhesive effect of acellular dermal matrix application after thyroid surgery: a multicenter randomized controlled trial.

Postoperative adhesions following thyroid surgery can lead to multiple complications that significantly impact quality of life. The use of an acellular dermal matrix (ADM) adhesion barrier device has been proposed as a potential solution to reduce the risk of such adhesions. This study aimed to evaluate the safety and anti-adhesive effect of an ADM in patients undergoing thyroid surgery. In this multicenter randomized controlled trial, patients undergoing thyroid surgery were randomly assigned to receive either ADM (n = 42) or no ADM (n = 39) during surgery. The primary outcome was the Swallowing Impairment Score (SIS-6), measured 6 weeks after surgery and compared between groups. Secondary outcomes included intergroup comparisons of the SIS-6, the Voice Handicap Index (VHI)-10, and the Glasgow-Edinburgh Throat Scale (GETS) at baseline, and 2, 6, and 18 weeks after surgery. At week 6, the mean SIS-6 scores were 4.0 ± 4.1 and 3.3 ± 4.2 in the ADM and control groups, respectively, which was not significantly different. Both groups showed similar postoperative improvements in SIS-6, VHI-10, and GETS scores over time, without significant differences between groups at any time point, indicating that the ADM did not reduce the incidence of postoperative adhesions or alter the course of recovery compared to the control group. Although application of the ADM is safe for use in patients undergoing thyroid surgery, it did not produce a clinically significant advantage in preventing postoperative adhesions. Future research should focus on identifying specific patient populations or surgical scenarios where the use of the ADM may be beneficial.

Fumaria officinalis Dust as a Source of Bioactives for Potential Dermal Application: Optimization of Extraction Procedures, Phytochemical Profiling, and Effects Related to Skin Health Benefits.

Fumaria officinalis (fumitory), in the form of dust, was employed as a source of bioactive extracts whose chemical profile and biological potential were investigated. According to the results of the optimization of the extraction protocol, the extract with the highest polyphenol yield was prepared using fumitory dust under the optimal conditions determined using the statistical tool, 23 full factorial design: 50% ethanol and a 30:1 mL/g ratio during 120 s of microwave extraction (22.56 mg gallic acid equivalent/g of plant material). LC-MS and spectrophotometric/gravimetric analyses quantified the polyphenol, flavonoid, tannin, alkaloid, and protein contents. Caffeoylmalic acid, quercetin dihexoside, quercetin pentoside hexoside, rutin, and methylquercetin dihexoside were the most dominant compounds. The highest total flavonoid, condensed tannin, alkaloid, and protein yields were determined in the extract prepared using microwaves. In addition to the proven antioxidant potential, in the present study, the anti-inflammatory activity of fumitory extracts is also proven in the keratinocyte model, as well as a significant reduction of H2O2-induced reactive oxygen species production in cells and the absence of keratinocyte cytotoxicity. Thus, detailed chemical profiles and investigated biological effects related to skin health benefits encourage the potential application of fumitory dust extracts in dermo-cosmetic and pharmaceutical preparations for dermatological circumstances.

Hydrogels of Poly(2-hydroxyethyl methacrylate) and Poly(N,N-dimethylacrylamide) Interpenetrating Polymer Networks as Dermal Delivery Systems for Dexamethasone.

Background/Objectives: This study is an attempt to reveal the potential of two types of interpenetrating polymer network (IPN) hydrogels based on poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(N,N-dimethylacrylamide) (PDMAM). These IPNs were evaluated for their potential for dermal delivery of the hydrophobic drug dexamethasone (DEX). Methods: The two types of IPNs were analyzed for their rheological behavior, swelling characteristics, and drug-loading capacity with DEX. Drug release profiles were studied in Franz diffusion cells in PBS media. Finally, the cytotoxicity of the PHEMA/PDMAM-based IPNs was studied against T-cell lymphoma cells (HUT-78) and a normal murine fibroblast cell line (CCL-1). Results: The rheological properties of these hydrogels show suitable mechanical properties for dermal application, with G' values of ~10 kPa. From the rheological data, the mesh size of these hydrogels was found to be influenced by the type of the IPN and its composition, varying between 6.5 and 50 nm. The loading capacity of both IPN types and DEX entrapment efficiency were highly influenced by the IPN's composition. The loading capacity of the IPNs can reach ~3.5%, with a DEX entrapment efficiency of ~35%. The PHEMA/PDMAM IPNs demonstrate an extended release profile with up to ~95% DEX released in 24 h, while PDMAM/PHEMA IPNs release no more than ~25% DEX in 24 h. The drug release profiles follow either non-Fickian diffusion (n~0.6) or case-II transport (n~0.9-1), depending on the IPN's composition. The PHEMA/PDMAM-based materials were found to be non-cytotoxic against HUT-78 and CCL-1 cells. Conclusions: The study reveals that the IPNs of PHEMA and PDMAM appear to be suitable platforms for dermal delivery of dexamethasone as they have appropriate mechanical properties, providing tools to control drug loading and release, and they are biocompatible with human skin cells.

Peptide Nanofibers and Skin Regeneration.

Peptide nanofibers have been attractive targets for regenerative medicine applications due to their tailorability to be easily functionalized for specific bioactivity, biocompatibility, ease of synthesis, adjustability of their physicochemical characteristics, and lack of biological contamination. Research groups have investigated their use for the regeneration of various tissues, such as bone, cartilage, brain, peripheral nerves, cardiac tissue, vascular tissues, endocrine cells, muscles, etc., for the treatment of degenerative diseases or tissue loss due to accidents or aging. Wound healing and skin regeneration are among the most widely investigated research areas for peptide nanofibers as well. In this article, we reviewed the literature on the utilization of peptide nanofibers for various skin regeneration and dermal healing applications, aiming to give the readers a general view of how peptide nanofibers have been used for this purpose so far as well as provide new insight on which avenues more research is necessary to be able to apply these methods in clinics.

Acellular Dermal Matrices in Reconstructive Pediatric Complex Lower Limb Trauma: An Observational Study.

Contemporary research has shown that acellular dermal matrices can benefit adult lower extremity traumatic injuries; however, its use in children has not been explored. This study aims to explore the use of acellular dermal matrices in pediatric complex lower extremity trauma. This single-center retrospective observational cohort study of children with complex lower extremity trauma treated with Pelnac™, commercial acellular dermal matrices, was conducted at a tertiary hospital in South Africa from 2010 to 2017. Demographic and clinical data were collected from medical records. The primary outcome was the rate and type of acellular dermal matrices-related complications. Secondary outcomes included the usage of negative pressure wound therapy. A total of 54 children were studied; 30 (55%) were male, and the median age was six. Forty-five children healed without complications, while nine experienced complications - four acute and five chronic. Four patients had complete loss of acellular dermal matrices, and three developed acute infections. More than 30days post-acellular dermal matrices application, five patients had hypertrophic scarring, four had joint contractures, and two had non-healing wounds. All patients who healed without complication received negative pressure wound therapy (n =45), while those who did not (n =5) developed complications. Three of the five patients without negative pressure wound therapy had acute acellular dermal matrices loss, compared to only one of the 49 patients who received negative pressure wound therapy. Our findings suggest that acellular dermal matrices may be an effective and safe reconstructive adjunct or alternative when used with negative pressure wound therapy.

Exploring the dermal safety of green-synthesized Ag-TiO2 nanocomposites for topical applications.

We investigated Ag-TiO2 nanocomposites (NCs) synthesized using leaf extracts of Azadirachta indica and Mangifera indica for topical applications. The Ag-TiO2 NCs were first characterized by their spherical shapes, with sizes ranging from 20-26 nm to 5-6 nm, and a zeta potential value between -27 and -23 mV. DLS analysis revealed average particle sizes of 671 nm and 573 nm for Ag-TiO2 NCs synthesized from A. indica and M. indica, respectively. The MICs of the nanocomposites were determined via dilution in both Gram-positive and Gram-negative bacteria to determine the optimal concentration for dermal applications. The cytotoxicity assay (MTT) of ATN and ATM compounds at MICs of 312.5 μg mL-1, 625 μg mL-1, and 1250 μg mL-1 showed that they were nontoxic to fibroblast cells. Further assessments of acute and subacute dermal safety were conducted on Charles Foster rats with NCs applied at 625 μg mL-1, 3125 μg mL-1, and 6250 μg mL-1 concentrations. Observations were made for any signs of dermal toxicity using behavioural and physical indices. In acute dermal toxicity, the NCs were applied once, and in subacute dermal toxicity, NCs were applied once daily for 28 days and observed for any sign of dermal toxicity using observation indices like behavioural changes, edema scores, and erythema scores. Post-experiment analyses of body weight, serum biochemistry, oxidative stress, and hematological profiles revealed that the nanocomposites exhibited significant antimicrobial activity. Notably, the safety evaluations indicated no adverse changes, suggesting these NCs are well-tolerated for dermal applications and show great promise for future topical applications.

Fabrication and Physio-chemical characterization of Biocompatible and Antibacterial Vitis Vinifera(grapes) loaded PVA Nanomembranes for Dermal Applications

Fabrication and Physio-chemical characterization of Biocompatible and Antibacterial Vitis Vinifera(grapes) loaded PVA Nanomembranes for Dermal Applications