Search Results (154)

Background: Hypertension affects 32% of adults worldwide, leading to a significant global consumption of cardiovascular medications. Atenolol, a β-adrenergic receptor blocker, is widely prescribed for cardiovascular diseases such as hypertension, angina pectoris, and myocardial infarction. According to the Biopharmaceutics Classification System (BCS), atenolol belongs to Class III, characterized by high solubility but low permeability. Currently, atenolol is commercially available in oral formulations. Increasing attention is being directed towards developing cost-effective transdermal delivery systems, due to their ease of use and better patient compliance. Eutectogels represent next-generation systems that are attracting great interest in the scientific community. Typically obtained from deep eutectic solvents (DESs) combined with gelling agents, these systems exhibit unique properties due to the intrinsic characteristics of DESs. Methods: In this study, a DES based on choline chloride as a hydrogen bond acceptor (HBA) and propylene glycol as a hydrogen bond donor (HBD) was explored to enhance the topical delivery of atenolol. The solubility of atenolol in the DES was evaluated using spectroscopic and thermodynamic measurements which confirmed the formation of hydrogen bonds between the drug and DES components. Additionally, the safety of the DES was assessed in a cell viability assay. Subsequently, we formulated eutectogels with different concentrations using animal gelatin and Tego Carbomer 140, and characterized these formulations through rheological measurements, swelling percentage, and permeation studies with Franz cells. Results: These novel eutectogels exhibit superior performance over conventional hydrogels, with a release rate of approximately 86% and 51% for Carbomer- and gelatin-based eutectogels, respectively. In contrast, comparable hydrogels released only about 27% and 35%. Conclusions: These findings underscore the promising potential of eutectogels for the transdermal delivery of atenolol. Full article

Species of the genus Kalanchoe have a long history of therapeutic use in ethnomedicine, linked to their remarkable medical properties. These species include Kalanchoe blossfeldiana succulents, which grow in tropical regions. Despite the great interest in this plant, there are no reports about its therapeutic effects on the skin. In this study, the antioxidant properties of K. blossfeldiana ethanol extracts and the skin permeation of a topical hydrogel containing the extract (HKB) were assessed. Additionally, the content of active compounds in the K. blossfeldiana extract was evaluated by UHPLC-MS and HPLC-UV. The extract was analyzed with three antioxidant assays: ABTS, DPPH, and FRAP. Furthermore, the antielastase and antihialuronidase properties of the tested extract were assessed. Ex vivo penetration studies were performed using the Franz diffusion cells. The estimation of the cytotoxicity of HKB was performed by using an MTT assay ((4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) on the human fibroblasts HFF-1. The results obtained show that the antioxidant properties of K. blossfeldiana extract were similar to those of ascorbic acid, while antielastase and antihialuronidase tests indicated the strong antiaging and anti-inflammatory activity of the extract (IC₅₀ was 26.8 ± 0.13 and 77.31 ± 2.44 µg/mL, respectively). Moreover, active ingredients contained in K. blossfeldiana extract penetrated through the human skin and accumulated in it. The cytotoxicity test showed that HKB had no significant effect on human fibroblasts at a concentration up to 0.5%. In conclusion, the hydrogel containing the K. blossfeldiana extract can be considered as an interesting and new alternative to dermatologic and cosmetic preparations. Full article

Imipramine hydrochloride (IMP), a tricyclic antidepressant used for major depression, enuresis, and neuropathic pain, is limited by gastrointestinal complications, low oral bioavailability (44%), and complex dosing requirements. This study aimed to explore a novel non-invasive nasal delivery system using chitosan nanoparticles (Cs NPs) embedded in an in situ gel to address the limitations of oral IMP administration. Cs NPs loaded with IMP were synthesized via ionic gelation and assessed for precision in drug concentration using a validated HPLC method. The particles were integrated into a thermoresponsive polymer, Pluronic F127, to form an in situ gel suitable for nasal administration. The formulation was characterized for gelation temperature, duration, viscosity, mucoadhesive strength, and overall gel robustness. Drug release kinetics and the controlled release mechanism were studied using ex vivo permeation tests with Franz diffusion cells and nasal sheep mucosa. The optimized nanoparticle formulation (F4-50) exhibited a consistent PS of 141.7 ± 2.2 nm, a zeta potential (ZP) of 16.79 ± 2.1 mV, and a high encapsulation efficiency of 67.71 ± 1.9%. The selected in situ gel formulation, F4-50-P1, demonstrated a gelation temperature of 33.6 ± 0.94 °C and a rapid gelation time of 48.1 ± 0.7 s. Transform-attenuated total reflectance infrared spectroscopy (ATR-IR) confirmed the compatibility and effective encapsulation of IMP within the formulation. The release profile of F4-50 included an initial burst release followed by a sustained release phase, with F4-50-P1 showing improved control over the burst release. The flux rates were 0.50 ± 0.01 mg/cm²/h for F4-50 and 0.33 ± 0.06 mg/cm²/h for F4-50-P1, indicating effective permeation. The developed chitosan nanoparticle-based in situ gel formulation provides a promising approach for the controlled release of IMP, enhancing therapeutic efficacy and patient compliance while mitigating the disadvantages associated with oral delivery. Full article

(1) Background: The present study aimed to assess the antifungal effectiveness of a topical innovative formulation containing the association of an antifungal agent, voriconazole (VCZ), and the essential oil of Pinus sylvestris L. (PSEO). (2) Methods: Pseudo-ternary phase diagram and D-optimal mixture design approaches were applied for the development and the optimization of the o/w nanoemulsion. The optimized formulation (NE) was subjected to physicochemical characterization and to physical stability studies. In vitro permeation studies were carried out using the Franz cell diffusion system. The antimycotic efficacy against Microsporum canis was carried out in vitro. (3) Results: Optimal nanoemulsion showed great physical stability and was characterized by a small droplet size (19.015 nm ± 0.110 nm), a PDI of 0.146 ± 0.011, a zeta potential of −16.067 mV ± 1.833 mV, a percentage of transmittance of 95.352% ± 0.175%, and a pH of 5.64 ± 0.03. Furthermore, it exhibited a significant enhancement in apparent permeability coefficient (p < 0.05) compared to the VCZ free drug. Finally, NE presented the greatest antifungal activity against Microsporum canis in comparison with VCZ and PSEO tested alone. (4) Conclusions: These promising results suggest that this topical innovative formulation could be a good candidate to treat onychomycosis. Further ex vivo and clinical investigations are needed to support these findings. 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

Chitosan (CS) has a natural origin and is a biodegradable and biocompatible polymer with many skin-beneficial properties successfully used in the cosmetics and pharmaceutical industry. CS derivatives, especially those synthesized via a Schiff base reaction, are very important due to their unique antimicrobial activity. This study demonstrates research results on the use of hydrogel microspheres made of [chitosan-graft-poly(ε-caprolactone)]-blend-(ĸ-carrageenan)], [chitosan-2-pyridinecarboxaldehyde-graft-poly(ε-caprolactone)]-blend-(ĸ-carrageenan), and chitosan-sodium-4-formylbenzene-1,3-disulfonate-graft-poly(ε-caprolactone)]-blend-(ĸ-carrageenan) as innovative vitamin carriers for cosmetic formulation. A permeation study of retinol (vitamin A), L-ascorbic acid (vitamin C), and α-tocopherol (vitamin E) from the cream through a human skin model by the Franz Cell measurement system was presented. The quantitative analysis of the release of the vitamins added to the cream base, through the membrane, imitating human skin, showed a promising profile of its release/penetration, which is promising for the development of a cream with anti-aging properties. Additionally, the antibacterial activity of the polymers from which the microspheres are made allows for the elimination of preservatives and parabens as cosmetic formulation ingredients. Full article

UV irradiation causes skin damage and aging. This study aimed to develop and evaluate a gel formulation loaded with electrospray mangiferin nanoparticles (MNPs) as a double-action product with photoprotective and anti-aging properties. The MNPs were prepared using the electrospraying technique and loaded in a gel formulation. The MNP formulation was evaluated regarding its physical appearance, viscosity, in vitro sun protection factor (SPF), and in vitro anti-oxidant activity and compared with a formulation containing purified mangiferin (PM) at the same concentration of 0.2% (w/v). Moreover, both formulations were analyzed for their in vitro release and ex vivo skin permeation. The MNP formulation had a considerably higher SPF value than the PM formulation at the same concentration (20.43 ± 0.13 and 12.19 ± 0.27, respectively). The in vitro anti-oxidant activities of the formulations with MNPs and PM were 74.47 ± 2.19% and 80.52 ± 1.05%, respectively. The MNP formulation showed potent photoprotective and anti-oxidation activities with acceptable stability in all parameters under accelerated conditions (4 ± 2 °C 48 h/45 ± 2 °C 48 h for 6 cycles) and after 30 days of storage under various conditions. The release profile data of the MNPs showed a controlled release pattern at 76.97 ± 0.06% at 480 min. Furthermore, after using a Franz diffusion cell for 8 h, the MNP formulation showed the release of 37.01 ± 2.61% and 22.39 ± 1.59% of mangiferin content in the skin layer as stratum corneum and viable epidermis, respectively. Therefore, the overall results demonstrate that electrospray MNPs in a gel formulation are suitable for skin and constitute a promising delivery system for mangiferin in developing cosmetics and cosmeceutical products with good potential. Full article

Recently, the number of people acquiring tattoos has increased, with tattoos gaining significant popularity in people between 20 and 40 years old. Inflammation is a common reaction associated with tattooing. The purpose of this study was to evaluate a nanostructured lipid carrier loading pranoprofen (PRA-NLC) as a tattoo aftercare formulation to reduce the inflammation associated with tattooing. In this context, the in vitro drug release and the ex vivo permeation-through-human-skin tests using Franz cells were appraised. The tolerance of our formulation on the skin was evaluated by studying the skin’s biomechanical properties. In addition, an in vivo anti-inflammatory study was conducted on mice skin to evaluate the efficacy of the formulation applied topically after tattooing the animals. PRA-NLC showed a sustained release up to 72 h, and the amount of pranoprofen retained in the skin was found to be 33.48 µg/g/cm². The formulation proved to be well tolerated; it increased stratum corneum hydration, and no signs of skin irritation were observed. Furthermore, it was demonstrated to be non-cytotoxic since the cell viability was greater than 80%. Based on these results, we concluded that PRA-NLC represents a suitable drug delivery carrier for the transdermal delivery of pranoprofen to alleviate the local skin inflammation associated with tattooing. Full article

Currently, the application of solvent exchange-induced in situ gel is underway for drug delivery to the body target site. Nitrocellulose was attempted in this research as the matrix-forming agent in solvent exchange-induced in situ gel for acne and periodontitis treatments. The gel incorporated a combination of 1% w/w levofloxacin HCl and 2% w/w salicylic acid as the active compounds. In order to facilitate formulation development, the study explored the matrix-forming behavior of different concentrations of nitrocellulose in N-methyl pyrrolidone (NMP). Consequently, their physicochemical properties and matrix-forming behavior, as well as antimicrobial and anti-inflammatory activities, were evaluated using the agar cup diffusion method and thermal inhibition of protein denaturation in the egg albumin technique, respectively. All prepared formulations presented as clear solutions with Newtonian flow. Their contact angles on agarose gel were higher than on a glass slide due to matrix formation upon exposure to the aqueous phase of agarose, with an angle of less than 60° indicating good spreadability. Nitrocellulose concentrations exceeding 20% initiated stable opaque matrix formation upon contact with phosphate buffer pH 6.8. The high hardness and remaining force of the transformed gel indicated their robustness after solvent exchange. Fluorescence tracking using sodium fluorescein and Nile red confirmed the retardation of NMP and water diffusion by the nitrocellulose matrix. From the Franz cell permeation study, these drugs could permeate through neonate porcine skin and tissue of porcine buccal from the nitrocellulose in situ forming gel. Their accumulation in these tissues might enable the inhibition of the invading bacterial pathogens. The developed in situ gels effectively inhibited Staphylococcus aureus, Staphylococcus epidermidis, Propionibacterium acnes, and Porphyromonas gingivalis. Furthermore, the formulations demonstrated an anti-inflammatory effect. The low viscosity of LvSa25Nc makes it appropriate for injectable treatments targeting periodontitis, while the higher viscosity of LvSa40Nc renders it appropriate for topical applications in acne treatment. Therefore, the nitrocellulose in situ gel loaded with combined levofloxacin HCl and salicylic acid emerges as a promising dosage form for treating acne and periodontitis. 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

Medicated foams have emerged as promising alternatives to traditional carrier systems in pharmaceutical research. Their rapid and convenient application allows for effective treatment of extensive or hirsute areas, as well as sensitive or inflamed skin surfaces. Foams possess excellent spreading capabilities on the skin, ensuring immediate drug absorption without the need for intense rubbing. Our research focuses on the comparison of physicochemical and biopharmaceutical properties of three drug delivery systems: foam, the foam bulk liquid, and a conventional hydrogel. During the development of the composition, widely used diclofenac sodium was employed. The safety of the formulae was confirmed through an in vitro cytotoxicity assay. Subsequently, the closed Franz diffusion cell was used to determine drug release and permeation in vitro. Ex vivo Raman spectroscopy was employed to investigate the presence of diclofenac sodium in various skin layers. The obtained results of the foam were compared to the bulk liquid and to a conventional hydrogel. In terms of drug release, the foam showed a rapid release, with 80% of diclofenac released within 30 min. In summary, the investigated foam holds promising potential as an alternative to traditional dermal carrier systems, offering faster drug release and permeation. 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

Diesel particulate matter is one of the most dangerous environmental stressors affecting human health. Many plant-derived compounds with antioxidant and anti-inflammatory properties have been proposed to protect the skin from pollution damage. Curcumin (CUR) has a plethora of pharmacological activities, including anticancer, antimicrobial, anti-inflammatory and antioxidant. However, it has low bioavailability due to its difficult absorption and rapid metabolism and elimination. CUR encapsulation in nanotechnological systems and its combination with biopotentiators such as piperine (PIP) can improve its pharmacokinetics, stability and activity. In this study, ethosomes (ETs) were investigated for CUR and PIP delivery to protect the skin from damage induced by diesel particulate matter. ETs were produced by different strategies and characterized for their size distribution by photon correlation spectroscopy, for their morphology by transmission electron microscopy, and for their drug encapsulation efficiency by high-performance liquid chromatography. Franz cells enabled us to evaluate in vitro the drug diffusion from ETs. The results highlighted that ETs can promote the skin permeation of curcumin. The studies carried out on their antioxidant activity demonstrated an increase in the antioxidant power of CUR using a combination of CUR and PIP separately loaded in ETs, suggesting their possible application for the prevention of skin damage due to exogenous stressors. Ex vivo studies on human skin explants have shown the suitability of drug-loaded ETs to prevent the structural damage to the skin induced by diesel engine exhaust exposure. Full article