Search Results (60)

Zeolites are microporous aluminosilicate minerals widely recognized for their adsorption and ion-exchange properties. Their capacity to capture toxic heavy metals has prompted growing interest in their use as anti-pollution agents in skin care formulations. This study investigates zeolite-based creams through an in vitro permeation test using Franz diffusion cells within a Quality by Design (QbD) framework. A 2 × 2 × 2 full factorial design was applied to evaluate the effects of three critical factors: membrane type (Strat-M^® vs. silicone), dosage (10 vs. 20 mg), and dosage regimen. The adsorption and retention of five heavy metals, cadmium (Cd), cobalt (Co), chromium (Cr), lead (Pb), and nickel (Ni), were assessed over 12 h using an in vitro membrane model. The cream containing Zeolite demonstrated significantly higher adsorption of Cr, Co, and Cd compared to placebo and membrane controls, while Ni and Pb exhibited less consistent patterns. No sampling of the receptor compartment was performed; therefore, the analysis focused on metal residues in the donor and membrane compartments. Statistical analyses confirmed the significance of these findings, and graphical trends further supported zeolite’s selective adsorption behavior. Overall, the results provide mechanistic and statistical evidence supporting zeolite as a promising active ingredient for the development of anti-pollution skin care formulations and offer a methodological framework for assessing metal adsorption in topical products. Full article

Background/Objectives: The treatment of atopic dermatitis frequently involves using a topical corticosteroid and a moisturizer. While the sequential application of these products is a common dermatological practice, their influence on drug penetration remains poorly understood. There is no clear evidence on how hydration, application sequence, and massage affect cutaneous drug delivery. Hence, this study aimed to evaluate the effects of formulation type, moisturizer composition, application sequence, and mechanical stimulation on betamethasone dipropionate (BET) cutaneous penetration. Methods: Two commercial formulations (cream and ointment) of BET were evaluated in different experimental conditions, including drug application combined with moisturizers (Cetaphil^®, as an emollient; Nivea^®, as an occlusive) pre- or post-application, with or without a 30 s massage. In vitro skin penetration assays were conducted for 12 h using porcine skin mounted in modified Franz diffusion cells. BET levels were extracted from the skin layers and quantified by HPLC. Results: The cutaneous BET penetration was strongly influenced by the application sequence, type of moisturizer, and mechanical stimuli. Pre-application of an occlusive or emollient moisturizer, followed by 30 s physical stimuli, significantly enhanced drug retention in the stratum corneum. For the cream, pre-application of moisturizers followed by massage notably increased BET levels in both the stratum corneum and viable skin. Conversely, post-application of moisturizers hindered BET absorption. The ointment showed limited penetration across all conditions, with no drug detected in the viable skin. Conclusions: The results showed pre-hydrating the skin, combined with a 30 s massage, was the best strategy for BET diffusion into the skin following cream administration. The formulation type and the order of application directly influence the effectiveness of drug therapy and the topical absorption of BET. Full article

Skin infections are common in veterinary practice and are often treated with topical agents. Superficial pyoderma (superficial bacterial folliculitis) is a common cause of skin disease in dogs and a reason for treatment, most caused by Staphylococcus spp. strains. The frequent use of antibiotics contributes to the emergence of resistant bacterial strains, making antimicrobial resistance (AMR) one of the most important threats to human and animal health. For this reason, active natural compounds are increasingly being explored as alternative therapies. To contribute to the development of effective treatments for bacterial infectious diseases, researchers are looking for new antimicrobial agents. Topical drug action has many advantages as it avoids systemic reactions and ensures that the active substance reaches the site of the lesion directly. This study aimed to develop gelled dosage forms with propolis extract and to evaluate their antibacterial activity and the release of the active substances. Hydrogels, oleogels, and bigels enriched with eutectic propolis extract were produced. Deep eutectic solvents (DESs) were chosen as an effective tool to extract the active compounds of propolis and to improve their penetration into the skin. The pH values of the semi-solid pharmaceutical forms tested ranged from 3.3 to 6.4. Using modified Franz-type diffusion cells, the release of phenolic compounds from gels, oleogels, and bigels was assessed and quantified spectrophotometrically using the Folin–Ciocalteu method. The highest amount of active compounds was released from the hydrogels, while the lowest amount was released from the castor oil-based oleogel. The study used clinical and reference strains of bacteria. The antimicrobial activity of the gelled dosage forms with propolis extract was tested against six pathogenic bacterial species (S. aureus, S. agalactiae, B. cereus, E. faecalis, E. coli, Ps. aeruginosa) and one pathogenic fungus (C. albicans). The study’s results suggest that the propolis extract obtained by DES has significant antibacterial activity and is a promising component in skin formulations for the treatment of bacterial infections. Full article

Background/Objectives: Since 2008, following clinical studies conducted on children that revealed the ability of the β-adrenergic antagonist propranolol to inhibit capillary growth in infantile hemangiomas (IHs), its oral administration has become the first-line treatment for IHs. Although oral propranolol therapy at a dosage of 3 mg/kg/die is effective, it can cause systemic adverse reactions. This therapy is not necessarily applicable to all patients. Topical skin applications could help maintain a high drug concentration at local sites and also represent a characteristically easy method of administration for pediatric patients. Because no topical propranolol dosage forms are commercially available, such formulations may be prepared at hospitals and pharmacies. Methods: In the present study, we identified a simple method for preparing topical propranolol hydrochloride formulations at 1% w/w with five commercial ready-to-use bases and evaluated the pharmaceutical profiles. The physical stability of the extemporaneous formulations was predicted by performing an accelerated centrifuge test and assessed by visual inspection after one month storage at 25 °C. The chemical stability of the drug in the five formulations was assessed by using a high-performance liquid chromatography (HPLC) method. In vitro drug-release and permeability experiments were conducted through synthetic membranes and the outer pavilion of a pig’s ear by utilizing Franz-type diffusion cells. Results: The results indicated that the release of the drug was significantly influenced by the internal structure and physicochemical properties of each base. Conclusions: Specifically, the formulations prepared with the hydrophilic bases could be easily prepared and yield satisfactory results, representing a potential effective therapy for IHs in pediatric patients. Full article

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. Full article

Background: This study explored the most suitable materials for incorporating cyano-phycocyanin (C-PC) into hydrogels, focusing on maintaining the C-PC’s long-term structural integrity and stabilityNext, the release of C-PC from the hydrogels and its skin penetration were investigated. Methods: A series of 1% (w/w) C-PC hydrogels was prepared using various gelling agents and preservatives. Spectrophotometric measurements compared the amount of C-PC in the hydrogels to the initially added amount. After selecting the most suitable gelling agent and preservative, two C-PC hydrogels, with and without propylene glycol (PG) (Sigma-Aldrich, St. Louis, MO, USA), were produced for further testing. In vitro release studies utilized modified Franz-type diffusion cells, while ex vivo skin-permeation studies employed Bronaugh-type cells and human skin. Confocal laser scanning microscopy analyzed C-PC accumulation in the skin. Results: The findings demonstrated that sodium alginate (Sigma-Aldrich, St. Louis, MO, USA), hydroxyethyl cellulose (HEC) (Sigma-Aldrich, St. Louis, MO, USA), and Soligel^TM (Givaudan, Vernier, Switzerland) are effective biopolymers for formulating hydrogels while maintaining C-PC stability. After 6 h, C-PC release from the hydrogel containing PG was approximately 10% or 728.07 (±19.35) μg/cm², significantly higher than the nearly 7% or 531.44 (±26.81) μg/cm² release from the hydrogel without PG (p < 0.05). The ex vivo qualitative skin-permeation study indicated that PG enhances C-PC penetration into the outermost skin layer. Conclusion: PG’s ability to enhance the release of C-PC from the hydrogel, coupled with its capacity to modify the skin barrier ex vivo, facilitates the penetration of C-PC into the stratum corneum. Full article

The article aims to outline the potential of treating malignant skin cancer with microneedles covered with polymer layers containing a photosensitizer—protoporphyrin IX disodium salt (PPIX). The usefulness of stereolithography (SLA), which is a form of 3D-printing technology, for the preparation of a microneedle system with protoporphyrin IX was demonstrated. The SLA method allowed for pyramid-shaped microneedles to be printed that were covered with three different 0.1% PPIX hydrogels based on sodium alginate, xanthan, and poloxamer. Rheological tests and microscopic analysis of the hydrogels were performed. Microneedles coated with two layers of poloxamer-based hydrogel containing 0.1% PPIX were subjected to release tests in Franz diffusion cells. The release profile of PPIX initially increased and then remained relatively constant. The amount of substance released after a four-hour test in three Franz cells was 0.2569 ± 0.0683 mg/cm². Moreover, the acute toxicity of this type of microneedle was assessed using the Microtox system. The obtained results show the usefulness of further development studies on microneedles as carriers of photosensitizing agents. Full article

Coumarins are benzopyrones found in several plant genera, including Pterocaulon (Asteraceae). These compounds represent an important source of new treatments, especially as antimicrobial and antifungal agents. In this study, two coumarin-rich extracts from Pterocaulon balansae using green technologies were obtained through aqueous maceration (AE) and supercritical fluid extraction (SFE). Such extracts were incorporated into nanoemulsions (NAE and NSFE) composed of a medium-chain triglyceride oil core stabilized by phospholipids. The nanoemulsions exhibited droplet sizes between 127 and 162 nm, pH above 5.0, and viscosity of approximately 1.0 cP, properties compatible with the topical route. The coumarins permeation/retention from formulations through ear porcine skin using Franz-type diffusion cells were evaluated. Whatever the extract, coumarins were distributed in skin layers, especially in the dermis in both intact and impaired (tape stripping) skin. In addition, a significant increase in coumarins that reached up to the receptor fluid was observed for impaired skin, with increases of approximately threefold for NAE and fourfold for NSFE. Finally, antifungal activity of nanoemulsions was evaluated according to minimum inhibitory concentrations, and the values were 250 µg/mL for all strains tested. The overall results demonstrated the feasibility of incorporating P. balansae extracts into nanoemulsions and showed a potential alternative for the treatment of sporotrichosis. Full article

Kombucha is a non-alcoholic beverage, that is increasingly used in the cosmetic industry. The available literature reports the positive effects of kombucha on the skin, in particular its antioxidant action. However, there is a lack of information on skin permeation and the accumulation of active ingredients showing such effects. Skin aging is largely dependent on oxidative stress, therefore in our study we assessed the ex vivo permeation of two types of kombucha (green and black tea) through porcine skin. The antioxidant activity (DPPH, ABTS, FRAP methods) and total polyphenol content of these extracts were determined before and after permeation testing. Moreover, the content of selected phenolic acids as well as caffeine was assessed. Skin permeation was determined using a Franz diffusion cell. The antioxidant activity of both Kombuchas was found to be high. In addition, gallic acid, chlorogenic acid, protocatechuic acid, coumaric acid, m-hydroxybenzoic acid, and caffeine were identified. A 24-h ex vivo study showed the permeation of some phenolic acids and caffeine and their accumulation in the skin. Our results confirm the importance of studying the skin permeation of what are still little known ingredients in cosmetic preparations. Evaluation of the accumulation of these ingredients can guarantee the efficacy of such preparations. Full article

Ropinirole is a non-ergolinic dopamine agonist used to manage Parkinson’s disease and it is characterized by poor oral bioavailability. This study aimed to design and develop advanced drug delivery systems composed of poloxamer 407, a non-ionic surfactant (Tween 80), and cyclodextrins (methyl-β-CD or hydroxy-propyl-β-CD) for possible brain targeting of ropinirole after nasal administration for the treatment of Parkinson’s disease. The hybrid systems were formed by the thin-film hydration method, followed by an extensive physicochemical and morphological characterization. The in vitro cytotoxicity of the systems on HEK293 cell lines was also tested. In vitro release and ex vivo mucosal permeation of ropinirole were assessed using Franz cells at 34 °C and with phosphate buffer solution at pH 5.6 in the donor compartment, simulating the conditions of the nasal cavity. The results indicated that the diffusion-controlled drug release exhibited a progressive increase throughout the experiment, while a proof-of-concept experiment on ex vivo permeation through rabbit nasal mucosa revealed a better performance of the prepared hybrid systems in comparison to ropinirole solution. The encouraging results in drug release and mucosal permeation indicate that these hybrid systems can serve as attractive platforms for effective and targeted nose-to-brain delivery of ropinirole with a possible application in Parkinson’s disease. Further ex vivo and in vivo studies to support the results of the present work are ongoing. Full article

The goal of this research was to study the factors influencing the in vitro transdermal penetration of nicotinamide and to establish an evaluation method for the in vitro transdermal absorption of nicotinamide. The permeability of nicotinamide was investigated with Franz diffusion cell in vitro transcutaneous assays, and the effect of the receiving solution composition, receiving solution pH, skin type, diffusion cell temperature, active ingredient concentration, supply quantity, and product dosage form on its permeation was investigated separately by high-performance liquid chromatography. The best assay for the transdermal absorption of nicotinamide was established—there was a better transdermal absorption performance, more stable system, better applicability, and better reproducibility when the receiving solution was PBS (phosphate-buffered saline) solution, the pH was 7.4, the membrane was pig ear skin, the temperature was 37 °C, the concentration of nicotinamide was 3%, and the dose of the test substance was 2 g. In the three cosmetic dosage forms of toning lotion, milk lotion, and gel, the permeability of milk lotion was the highest, followed by toning lotion and gel. Full article

Valsartan (Val) is an important antihypertensive medication with poor absorption and low oral bioavailability. These constraints are due to its poor solubility and dissolution rate. The purpose of this study was to optimize a mixed micelle system for the transdermal delivery of Val in order to improve its therapeutic performance by providing prolonged uniform drug levels while minimizing drug side effects. Thin-film hydration and micro-phase separation were used to produce Val-loaded mixed micelle systems. A variety of factors, including the surfactant type and drug-to-surfactant ratio, were optimized to produce micelles with a low size and high Val entrapment efficiency (EE). The size, polydispersity index (PDI), zeta potential, and drug EE of the prepared micelles were all measured. The in vitro drug release profiles were assessed using dialysis bags, and the permeation through abdominal rat skin was assessed using a Franz diffusion cell. All formulations had high EE levels exceeding 90% and low particle charges. The micellar sizes ranged from 107.6 to 191.7 nm, with average PDI values of 0.3. The in vitro release demonstrated a uniform slow rate that lasted one week with varying extents. F7 demonstrated a significant (p < 0.01) transdermal efflux of 68.84 ± 3.96 µg/cm²/h through rat skin when compared to the control. As a result, the enhancement factor was 16.57. In summary, Val-loaded mixed micelles were successfully prepared using two simple methods with high reproducibility, and extensive transdermal delivery was demonstrated in the absence of any aggressive skin-modifying enhancers. Full article

Animal models are still used in the research and development of ophthalmic drug products, mainly due to the difficulty in simulating natural physiological conditions with in vitro models, as there is a lack of dynamic protection mechanisms. Therefore, developing alternative ophthalmic models that evaluate drug penetration in the cornea while applying dynamic protection barriers is a contemporary challenge. This study aimed to develop a dynamic ex vivo model using porcine eyes with a simulated lacrimal flow to evaluate the performance of pharmaceutical drug products. A glass donor cell to support a simulated tear flow was designed, optimized, and custom-made. The system was challenged with different formulations (with fluconazole) including excipients with different viscosities (poloxamer 407) and mucoadhesive properties (chitosan). The results were compared to those obtained from a conventional excised cornea model mounted in Franz-type diffusion cells. The dynamic model could differentiate formulations, while the static model did not, overestimating ex vivo drug penetrated amounts. Hence, the dynamic model with simulated tear flow showed to be a simple and promising new alternative method for the drug penetration of ophthalmic formulations that ultimately can reduce the number of animals used in research. Full article

In this study, a new approach to pesticide permeation through the apple peel into the pulp is discussed. The tested compounds can be classified, based on mode of action, as systemic (boscalid, cyprodinil, pirimicarb, propiconazole and tebuconazole) or contact (captan, cypermethrin and fludioxonil) pesticides. The barrier effect was assessed using a Franz flow-type vertical diffusion cell system. A residue analysis was performed using a modified quick, easy, cheap, efficient, rugged and safe (QuEChERS) extraction method coupled to gas chromatography with tandem mass spectrometry (GC-MS/MS). The limits of detection (LODs) ranged between 2.6 µg kg⁻¹ (pirimicarb) and 17 µg kg⁻¹ (captan), with the coefficient of variability (CV) lower than 6%, while recoveries ranged from 85% (boscalid) to 112% (captan) at 0.1 and 1 mg kg⁻¹ spiked levels. The highest peel penetration was observed for pirimicarb, captan and cyprodinil, with cumulative permeations of 90, 19 and 17 µg cm⁻², respectively. The total absorption was in the range from 0.32% (tebuconazole) to 32% (pirimicarb). Only cypermethrin was not quantitatively detected in the pulp, and its use can be recommended in crop protection techniques. The obtained results indicate that molecular weight, octanol-water partition coefficient and water solubility are important parameters determining the process of pesticide absorption. Full article

The aim of this study was to assess the release profile of components in five different honeys (a New Zealand Manuka and two Western Australian honeys, a Jarrah honey and a Coastal Peppermint honey) and their corresponding honey-loaded gel formulations using a custom-designed Franz-type diffusion cell in combination with High-Performance Thin-Layer Chromatography (HPTLC). To validate the suitability of the customised setup, release data using this new approach were compared with data obtained using a commercial Franz cell apparatus, which is an established analytical tool to monitor the release of active ingredients from topical semisolid products. The release profiles of active compounds from pure honey and honey-loaded formulations were found to be comparable in both types of Franz cells. For example, when released either from pure honey or its corresponding pre-gel formulation, the percentage release of two Jarrah honey constituents, represented by distinct bands at R_F 0.21 and 0.53 and as analysed by HPTLC, was not significantly different (p = 0.9986) at 12 h with over 99% of these honey constituents being released in both apparatus. Compared to the commercial Franz diffusion cell, the customised Franz cell offers several advantages, including easy and convenient sample application, the requirement of only small sample quantities, a large diffusion surface area, an ability to analyse 20 samples in a single experiment, and lower cost compared to purchasing a commercial Franz cell. Thus, the newly developed approach coupled with HPTLC is conducive to monitor the release profile of minor honey constituents from pure honeys and honey-loaded semisolid formulations and might also be applicable to other complex natural-product-based products. Full article