Search Results (14)

This research paper presents an advanced exploration into the utilization of ultrasound-assisted extraction (UAE) combined with natural deep eutectic solvents (NADESs) to achieve higher concentrations of polyphenols from Graševina grape pomace. Focusing on optimizing extraction parameters to maximize the yield of polyphenols, this study evaluates their potential industrial applications, particularly within the food and cosmetics sectors. The effectiveness of betaine/glucose (BGlc) NADESs in producing stable, ready-to-use extracts with enhanced bioavailability and eco-friendly attributes is underscored. The integration of UAE with BGlc NADESs has shown significant scalability and applicability for industrial use, as evidenced by the extracts’ collagenase-inhibitory effects, determined using a ninhydrin-based colorimetric assay showing the significant inhibition of gelatine degradation and scratch tests on cultured skin cells, demonstrating enhanced cell migration and wound healing, indicating their potential in anti-aging cosmetic products. Additionally, the results from PAMPA tests demonstrated that NADES extraction significantly enhances the intestinal absorption of polyphenols from grape pomace extracts compared to conventional solvents, highlighting the potential of NADESs to improve the bioavailability of these compounds and offering promising implications for their application in the food industry. Furthermore, the research highlights the practicality of directly incorporating these extracts into products, such as anti-aging creams and functional foods, supporting sustainability initiatives within the cosmetic and food industries. This work aims to provide a comprehensive guide to green extraction techniques on a preparative scale, showcasing the versatility and innovative applications of NADES-extracted compounds across various industries, thereby paving the way for the development of eco-conscious and effective products. Full article

Centella asiatica extract is a valued plant material with known anti-inflammatory and anti-microbiological properties. Using the Design of Experiment (DoE) approach, it was possible to obtain an optimized water/alcoholic extract from Centella asiatica, which allowed the preparation of the final material with biological activity in the wound healing process. Studies on the novel applications of Centella asiatica in conjunction with the multifunctional chitosan carrier have been motivated by the plant’s substantial pharmacological activity and the need to develop new and effective methods for the treatment of chronic wounds. The controlled release of asiaticoside was made possible by the use of chitosan as a carrier. Based on the findings of investigations using the PAMPA skin assay, which is a model imitating the permeability of actives through skin, this compound, characterized by sustained release from the chitosan delivery system, was identified as being well able to permeate biological membranes such as skin. Chitosan and the lyophilized extract of Centella asiatica worked synergistically to block hyaluronidase, exert efficient microbiological activity and take part in the wound healing process, as proven in an in vitro model. A formulation containing 3% extract with 3% medium-molecular-weight chitosan was indicated as a potentially new treatment with high compliance and effectiveness for patients. Optimization of the chitosan-based hydrogel preparation ensured the required rheological properties necessary for the release of the bioactive from the chitosan delivery system and demonstrated a satisfactory antimicrobial activity. Full article

Two parallel artificial membrane permeability assay (PAMPA) systems intended for emulating skin permeability have been characterized through the solvation parameter model of Abraham using multilinear regression analysis. The coefficients of the obtained equations have been compared to the ones already established for other PAMPA membranes using statistical tools. The results indicate that both skin membranes are similar to each other in their physicochemical properties. However, they are different from other PAMPA membranes (e.g., intestinal absorption and blood–brain PAMPAs), mainly in terms of hydrophobicity and hydrogen bonding properties. Next, all PAMPA membranes have been compared to relevant biological processes also characterized through the solvation parameter model. The results highlight that skin-PAMPA membranes are a very good choice to emulate skin permeability. Full article

Aloe gel is a medicinal raw material with proven pharmacological activity. The health-promoting properties of other species of Aloe upon topical application prompted us to develop a formulation for the topical application of A. arborescence species. As a result of the gel preparation from the aqueous lyophilized extracts of three-year-old leaves of A. arborescence, no changes in the composition of the content of aloins A and aloenin A were found. The potential to neutralize free radicals was tested using DPPH and CUPRAC techniques, which confirmed the anti-radical activity of the lyophilisate. Screening of the inhibition of enzymes, the hyperactivity of which is associated with adverse changes in the skin of a pro-inflammatory nature, was performed. Importantly, using the PAMPA SKIN model, the possibility of the penetration of selected extract compounds (aloin A and aloenin A) through the skin was proven. Then, two formulations were prepared based on sodium alginate and hydroxypropyl methylcellulose (HPMC) and the hydrogels were characterized (rheological analysis, drug release profiles, permeability, and stability studies). HPMC-based hydrogel was the one with a targeted release of active substances and greater stability. Aloe arborescens hydrogel matrices seem to be a promising treatment strategy for inflammatory surface damage based on “green technology” at the stage of extract preparation and development of the drug form for topical application. Full article

In recent years, the study of dermal preparations has received increased attention. There are more and more modern approaches to evaluate transdermal formulations, which are crucial in proving the efficacy of a formulation. The aim of this study was to compare permeation across innovative synthetic membranes (Strat-M and Skin PAMPA membranes) and heat-separated human epidermis (HSE, gold standard membrane) using four different dermal formulations. The Strat-M and Skin PAMPA membranes were designed to mimic the stratum corneum layer of the human epidermis. There have also been some publications on their use in dermal formulation development, but further information is needed. Drug permeation was measured using formulations containing diclofenac sodium (two hydrogels and two creams). The HSE, Strat-M, and Skin PAMPA membranes proved to be significantly different, but based on the results, the Strat-M membrane showed the greatest similarity to HSE. The permeation data of the different formulations across different membranes showed good correlations with formulations similar to these four, which allows the prediction of permeation across HSE using these synthetic membranes. In addition, Strat-M and Skin PAMPA membranes have the potential to select and differentiate a dermal formulation containing diclofenac sodium as an early screening model. Full article

Absorption through the skin of topically applied chemicals is relevant for both formulation development and safety assessment, especially in the early stages of development. However, the supply of human skin is limited, and the traditional in vitro methods are of low throughput. As an alternative, an artificial membrane-based Skin Parallel Artificial Membrane Permeability Assay (Skin-PAMPA) has been developed to mimic the permeability through the stratum corneum. In this study, this assay was used to measure the permeability of a model compound, 4-phenylethyl-resorcinol (PER), dissolved in 13 different solvents that are commonly used in cosmetic formulation development. The study was performed at concentrations close to the saturated solution of PER in each solvent to investigate the maximum thermodynamic potential of the solvents. The permeability of PER in selected solvents was also measured on ex vivo pig skin for comparison. Pig ear skin is an accepted alternative model of human skin. The permeability coefficient, which is independent of the concentration of the applied solution, showed a good correlation (R² = 0.844) between the Skin-PAMPA and the pig skin permeation data. Our results support the use of the Skin-PAMPA to screen the suitability of different solvents for non-polar compounds at an early stage of formulation development. Full article

The study aimed to examine whether usnic acid—a lichen compound with UV-absorbing properties—can be considered as a prospective photoprotective agent in cosmetic products. Moreover, a comparison of two usnic acid enantiomers was performed to preselect the more effective compound. To meet this aim, an in vitro model was created, comprising the determination of skin-penetrating properties via skin-PAMPA assay, safety assessment to normal human skin cells (keratinocytes, melanocytes, fibroblasts), and examination of photostability and photoprotective properties. Both enantiomers revealed comparable good skin-penetrating properties. Left-handed usnic acid was slightly more toxic to keratinocytes (IC₅₀ 80.82 and 40.12 µg/mL, after 48 and 72 h, respectively) than its right-handed counterpart. The latter enantiomer, in a cosmetic formulation, was characterized by good photoprotective properties and photostability, comparable to the UV filter octocrylene. Perhaps most interestingly, (+)-usnic acid combined with octocrylene in one formulation revealed enhanced photoprotection and photostability. Thus, the strategy can be considered for the potential use of (+)-usnic acid as a UV filter in cosmetic products. Moreover, the proposed model may be useful for the evaluation of candidates for UV filters. Full article

The human skin is marked as a standard by the regulatory agencies in the permeation study of dermal formulations. Artificial membranes can substitute human skin to some extent. Academicians and pharmaceutical corporations are focusing their efforts on developing standardized protocols and safe, reliable options to substitute human skin for carrying out permeability studies. Our research aim was to study the applicability of new techniques in the case of different types of dermal formulations. The skin parallel artificial membrane permeability assay (PAMPA) method and Raman mapping were compared to the gold-standard Franz cell method. A hydrogel and two types of creams were investigated as the most generally used dermal preparations. The values of the diffused drug were closer to each other in PAMPA and Franz cell measurement. The diffused amount of drug showed the same order for the different formulations. These results correlate well with the results of Raman mapping. Our conclusions suggest that all early screening examinations can be performed with model tools such as skin PAMPA supplemented with methods like Raman mapping as a semi-quantitative method. Full article

Calendulae flos is a valued plant material with known anti-inflammatory and antimicrobiological properties. The limitation for its use in the treatment of chronic wounds is the lack of adhesion to the required site of action. Obtaining the Calendulae flos lyophilized extract from water-ethanolic extract allowed to prepare valuable material whose biological activity in the wound healing process was confirmed by a positive result of the scratch test. The Calendulae flos lyophilized extract was standardized for the contents of the chlorogenic acid and the narcissin. The significant potency of the Calendulae flos pharmacological activity has become the reason for studies on its novel applications in combination with the multifunctional chitosan carrier, to create a new, valuable solution in the treatment of chronic wounds. The use of chitosan as a carrier allowed for the controlled release of the chlorogenic acid and the narcissin. These substances, characterized by prolonged release from the chitosan delivery system, were identified as well permeable, based on the results of the studies of the parallel artificial membrane permeability assay (PAMPA Skin) a model simulating permeability through membrane skin. The combination of the Calendulae flos lyophilized extract and the chitosan allowed for synergy of action towards hyaluronidase inhibition and effective microbiological activity. Optimization of the hypromellose hydrogel preparation ensuring the required rheological properties necessary for the release of the chlorogenic acid and the narcissin from the chitosan delivery system, as well as demonstrated antimicrobial activity allows indicating formulations of 3% Calendulae flos lyophilized extract with chitosan 80/500 in weight ratio 1:1 and 2% or 3% hypromellose as an important support with high compliance of response and effectiveness for patients suffering from chronic wounds. Full article

The transdermal route of drugs has received increased attention in recent years due to numerous advantages over the oral and injectable routes, such as avoidance of the hepatic metabolism, protection of drugs from the gastrointestinal tract, sustained drug delivery, and good patient compliance. The assessment of ex vivo permeation during the pharmaceutical development process helps in understanding the product quality and performance of a transdermal delivery system. Generally, excised human skin relevant to the application site or animal skin is recommended for ex vivo permeation studies. However, the limited availability of the human skin and ethical issues surrounding the use of animal skin rendered these models less attractive in the permeation study. In the last three decades, enormous efforts have been put into developing artificial membranes and 3D cultured human skin models as surrogates to the human skin. This manuscript provides an insight on the European Medicines Agency (EMA) guidelines for permeation studies and the parameters affected when using Franz diffusion cells in the permeation study. The need and possibilities for skin alternatives, such as artificially cultured human skin models, parallel artificial membrane permeability assays (PAMPA), and artificial membranes for penetration and permeation studies, are comprehensively discussed. Full article

Niacinamide (NIA) is the amide form of vitamin B3 and has been widely used in pharmaceutical and personal care formulations. Previously, we reported a comparative study of NIA permeation from neat solvents using the Skin Parallel Artificial Membrane Permeability Assay (PAMPA) and mammalian skin. A good correlation between NIA permeation in the different models was found. In the present work, ten binary and ternary systems were evaluated for their ability to promote NIA delivery in the Skin PAMPA model, porcine skin and human epidermis. Penetration enhancement was evident for binary systems composed of propylene glycol and fatty acids in human skin studies. However, propylene glycol and oleic acid did not promote enhancement of NIA compared with other systems in the Skin PAMPA model. A good correlation was obtained for permeation data from Skin PAMPA and porcine skin. However, data from the Skin PAMPA model and from human skin could only be correlated when the PG-fatty acid systems were excluded. These findings add to our knowledge of the potential applications of Skin PAMPA for screening dermal/transdermal preparations. Full article

Dermal and transdermal drug therapy is increasing in importance nowadays in drug development. To completely utilize the potential of this administration route, it is necessary to optimize the drug release and skin penetration measurements. This review covers the most well-known and up-to-date methods for evaluating the cutaneous penetration of drugs in vitro as a supporting tool for pharmaceutical research scientists in the early stage of drug development. The aim of this article is to present various experimental models used in dermal/transdermal research and summarize the novel knowledge about the main in vitro methods available to study skin penetration. These techniques are: Diffusion cell, skin-PAMPA, tape stripping, two-photon microscopy, confocal laser scanning microscopy, and confocal Raman microscopic method. Full article

The aim of this research was to investigate the stability of a lidocaine-loaded nanostructured lipid carrier dispersion at different temperatures, formulate a nanostructured lipid carrier gel, and test the penetration profile of lidocaine from the nanostructured lipid carrier gel using different skin penetration modeling methods. The formulations were characterized by laser diffraction, rheological measurements and microscopic examinations. Various in vitro methods were used to study drug release, diffusion and penetration. Two types of vertical Franz diffusion cells with three different membranes, including cellulose, Strat-M^®, and heat separated human epidermis were used and compared to the Skin-parallel artificial membrane permeability assay (PAMPA) method. Results indicated that the nanostructured lipid carrier dispersion had to be gelified as soon as possible for proper stability. Both the Skin-PAMPA model and Strat-M^® membranes correlated favorably with heat separated human epidermis in this research, with the Strat-M^® membranes sharing the most similar drug permeability profile to an ex vivo human skin model. Our experimental findings suggest that even when the best available in vitro experiment is selected for modeling human skin penetration to study nanostructured lipid carrier gel systems, relevant in vitro/in vivo correlation should be made to calculate the drug release/permeation in vivo. Future investigations in this field are still needed to demonstrate the influence of membranes and equipment from other classes on other drug candidates. Full article

The permeation properties of twenty newly synthesized α-alkoxyalkanoyl and α-aryloxyalkanoyl C-21 esters of standard corticosteroids: Fluocinolone acetonide, dexamethasone, triamcinolone acetonide and hydrocortisone were established using a PAMPA assay (70% silicone oil and 30% isopropyl myristate). The data were compared with parent corticosteroids with addition of mometasone furoate and hydrocortisone acetate. All newly synthesized corticosteroid C-21 esters have effective permeability coefficients higher then -6, mostly followed with high values of retention factors and low permeation. The examined compounds were grouped through relationship between obtained retention factors and permeation parameters (groups I–III). The classification confirmed group I (membrane retentions as well as permeation lower then 30%) for all corticosteroid standards except mometasone furoate, a potent topical corticosteroid which, with high membrane retention (81%) and low permeation (7.7%) fits into group III. The largest number of new synthesized corticosteroids C-21 esters, among them all fluocinolone acetonide C-21 esters, have high membrane retentions (32.4%–86.5%) and low permeations (1.3%–27.1%), fitting in group III. The classification was related to previously obtained anti-inflammatory activity data for the fluocinolone acetonide C-21 esters series. According to the PAMPA results the new synthesized esters could be considered as potential new prodrugs with useful benefit/risk ratio. Full article