Formulation, Preparation, Characterization, and Evaluation of Dicarboxylic Ionic Liquid Donepezil Transdermal Patches

Donepezil (DPZ) is generally administered orally to treat Alzheimer’s disease (AD). However, oral administration can cause gastrointestinal side effects. Therefore, to enhance compliance, a new way to deliver DPZ from transdermal patch was developed. Ionic bonds were created by dissolving dicarboxylic acid and DPZ in ethanol, resulting in a stable ionic liquid (IL) state. The synthesized ILs were characterized by differential scanning calorimetry, optical microscope, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The DPZ ILs were then transformed to a suitable drug-in-adhesive patch for transdermal delivery of DPZ. The novel DPZ ILs patch inhibits crystallization of the IL, indicating coherent design. Moreover, DPZ ILs and DPZ IL patch formulations performed excellent skin permeability compared to that of the DPZ free-base patch in both in vitro and ex vivo skin permeability studies.

Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin–Hydroxybenzohydrazide Hybrids

Free radicals often interact with vital proteins, violating their structure and inhibiting their activity. In previous studies, synthesis, characterisation, and the antioxidative properties of the five different coumarin derivatives have been investigated. In the tests of potential toxicity, all compounds exhibited low toxicity with significant antioxidative potential at the same time. In this paper, the radical scavenging activity of the abovementioned coumarin derivatives towards ten different radical species was investigated. It was found that all investigated compounds show good radical scavenging ability, with results that are in correlation with the results published in the previous study. Three additional mechanisms of radical scavenging activity were investigated. It was found that all three mechanisms are thermodynamically plausible and in competition. Interestingly, it was found that products of the Double Hydrogen Atom Transfer (DHAT) mechanism, a biradical species in triplet spin state, are in some cases more stable than singlet spin state analogues. This unexpected trend can be explained by spin delocalisation over the hydrazide bridge and phenolic part of the molecule with a low probability of spin pairing. Besides radical-scavenging activity, the pharmacokinetic and drug-likeness of the coumarin hybrids were investigated. It was found that they exhibit good membrane and skin permeability and potential interactions with P-450 enzymes. Furthermore, it was found that investigated compounds satisfy all criteria of the drug-likeness tests, suggesting they possess a good preference for being used as potential drugs.

Concentration of Antioxidant Compounds from Calendula officinalis through Sustainable Supercritical Technologies, and Computational Study of Their Permeability in Skin for Cosmetic Use

The growing interest in the cosmetic industry in using compounds of natural and sustainable origin that are safe for humans is encouraging the development of processes that can satisfy these needs. Chlorogenic acid (CHA), caffeic acid (CAF) and ferulic acid (FA) are three compounds widely used within the cosmetic industry due to their functionalities as antioxidants, collagen modifiers or even as radiation protectors. In this work, two advanced separation techniques with supercritical CO2 are used to obtain these three compounds from Calendula officinalis, and these are then evaluated using a computational skin permeability model. This model is encompassed by the COSMO-RS model, the calculations of which make it possible to study the behaviour of the compounds in the epidermis. The results show that both CAF and FA are retained in the stratum corneum, while CHA manages to penetrate to the stratum spinosum. These compounds were concentrated by antisolvent fractionation with super-critical CO2 using a Response Surface Methodology to study the effect of pressure and CO2 flow rate. CHA, CAF and FA were completely retained in the precipitation vessel, with concentrations between 40% and 70% greater than in the original extract. The conditions predicted that the optimal overall yield and enrichment achieved would be 153 bar and 42 g/min.

Effect of Manufacturing and Absorption Promotion of Lidocaine Hydrogel Using Ultrasonic Waves during Cosmetic Procedures

Purpose: In this study, we study to more effectively use anesthesia products used in beauty procedures following the popularization of anti-aging. Hydrogel, which contains lidocaine, is believed to be more effective in relieving pain if used in cosmetic procedures with ultrasonic waves.Methods: The availability of manufactured hydrogels and commercial gels for ultrasonic treatment was compared, and the effect on skin penetration and skin penetration due to ultrasonic limitations was evaluated based on their applicability. Usability and optimal ultrasound parameters were identified during ultrasound treatment.Results: Viscosity measurement, gelation rate, swelling, skin permeability experiment, and HPLC analysis of manufactured hydrogels all revealed properties, with skin permeability being highest at frequency 1 MHz, cycle low 200, and high 50.Conclusions: Finally, hydrogels containing lidocaine increased skin permeability during ultrasound treatment, allowing for faster targeted transdermal transmission that was more effective depending on the ultrasound parameters. As a result, it is determined that it can be used in cosmetic procedures.

Ion-Pair Compounds of Strychnine for Enhancing Skin Permeability: Influencing the Transdermal Processes In Vitro Based on Molecular Simulation

This research aimed to explore how Strychnine (Str) ion-pair compounds affect the in vitro transdermal process. In order to prevent the influence of different functional groups on skin permeation, seven homologous fatty acids were selected to form ion-pair compounds with Str. The in vitro permeation fluxes of the Str ion-pair compounds were 2.2 to 8.4 times that of Str, and Str-C10 had the highest permeation fluxes of 42.79 ± 19.86 µg/cm2/h. The hydrogen bond of the Str ion-pair compounds was also confirmed by Fourier Transform Infrared (FTIR) Spectroscopy, Nuclear Magnetic Resonance (NMR) Spectroscopy and molecular simulation. In the process of molecular simulation, the intercellular lipid and the viable skin were represented by ceramide, cholesterol and free fatty acid of equal molar ratios and water, respectively. It was found by the binding energy curve that the Str ion-pair compounds had better compatibility with the intercellular lipid and water than Str, which indicated that the affinity of Str ion-pair compounds and skin was better than that of Str and skin. Therefore, it was concluded that Str ion-pair compounds can be distributed from the vehicle to the intercellular lipid and viable skin more easily than Str. These findings broadened our knowledge about how Str ion-pair compounds affect the transdermal process.

A Review on SLN and NLC for Management of Fungal Infections

Fungal disease is an invasive, serious, and systemic topical infection that affects the mucous membranes, tissues, and skin of humans. Oral medicines, on the other hand, have significant side effects, making topical treatments a viable alternative. Many antifungal medications applied through the skin in various conventional forms (gels or creams) may cause skin redness, erythema, stinging, and burning sensations. A promising approach to overcome the limitation of conventional form is the use of Nanocarriers for the treatment of skin infections since it allows targeted drug delivery, enhanced skin permeability, and controlled release and hence offers a lower risk of side effects. During the last few decades, lipid nanoparticles (LNPs) such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have gained a lot of attention. SLNs were designed to overcome the drawbacks of conventional colloidal carriers, such as emulsions, liposomes, and polymeric nanoparticles, by offering benefits such as a good release rate and drug targeting with high physical stability. NLCs are SLNs that have been modified (Second generation SLN) to improve stability and capacity loading. This review discusses the pathophysiology of the fungal diseases, the application of SLN and NLC, its method of preparation, Characterization, and an overview of clinical trials on SLN and NLC for the treatment of fungal infection.

Enhanced Skin Delivery of Therapeutic Peptides Using Spicule-Based Topical Delivery Systems

This study reports two therapeutic peptides, insulin (INS, as a hydrophilic model peptide) and cyclosporine A (CysA, as a hydrophobic one), that can be administrated through a transdermal or dermal route by using spicule-based topical delivery systems in vitro and in vivo. We obtained a series of spicules with different shapes and sizes from five kinds of marine sponges and found a good correlation between the skin permeability enhancement induced by these spicules and their aspect ratio L/D. In the case of INS, Sponge Haliclona sp. spicules (SHS) dramatically increased the transdermal flux of INS (457.0 ± 32.3 ng/cm2/h) compared to its passive penetration (5.0 ± 2.2 ng/cm2/h) in vitro. Further, SHS treatment slowly and gradually reduced blood glucose to 13.1 ± 6.3% of the initial level in 8 h, while subcutaneous injection resulted in a rapid blood glucose reduction to 15.9 ± 1.4% of the initial level in 4 h, followed by a rise back to 75.1 ± 24.0% of the initial level in 8 h. In the case of CysA, SHS in combination with ethosomes (SpEt) significantly (p < 0.05) increased the accumulation of CysA in viable epidermis compared to other groups. Further, SpEt reduced the epidermis thickness by 41.5 ± 9.4% in 7 days, which was significantly more effective than all other groups. Spicule-based topical delivery systems offer promising strategies for delivering therapeutic peptides via a transdermal or dermal route.

FORMULATION AND EVALUATION OF HERBAL ORAL EMULGEL CONTAINING PSIDIUM GUAJAVA LINN. LEAVES EXTRACT (A PREVENTIVE ORAL CARE PREPARATION)

Objective: The present research work is based to establish the formulation and evaluation of herbal oral emulgel containing extracts of powdered Psidium guajava Linn. leaves extract. Methods: The guava leaves were collected and extracted by cold maceration process using different solvents, further ethanolic extract was used for the emulgel preparation. Emulsion and gel phase were prepared separately and mixed together in ratio of 1:1. Results: Different formulations ere developed and evaluated for the physical appearance, pH, homogeneity, spreadability, viscosity, extrudability, antibacterial activity, and in vitro skin permeability studies. In all formulated emulgel containing P. guajava Linn. Leaves, extract F2 formulation gives all satisfactory results as in discuss in this paper. Conclusion: Overall, concluded that the extract might contain anti-bacterial properties and further tests are required to prove for oral care activity using other in vivo or in vitro techniques.

Novel Naproxen Salts with Increased Skin Permeability

The paper presents the synthesis, full identification, and characterization of new salts-L-proline alkyl ester naproxenates [ProOR][NAP], where R was a chain from ethyl to butyl (including isopropyl). All obtained compounds were characterized by Nuclear Magnetic Resonance (NMR), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffractometry (XRD), and in vitro dissolution studies. The specific rotation, phase transition temperatures (melting point), and thermal stability were also determined. In addition, their lipophilicity, permeability, and accumulation in pigskin were determined. Finally, toxicity against mouse L929 fibroblast cells was tested. The obtained naproxen derivatives showed improved solubility and higher absorption of drug molecules by biological membranes. Their lipophilicity was lower and increased with the increase in the alkyl chain of the ester. The derivative with isopropyl ester had the best permeability through pigskin. The use of L-proline isopropyl ester naproxenate increased the permeation of naproxen through the skin almost four-fold. It was also shown that the increase in permeability is not associated with additional risk: all compounds had a similar effect on cell viability as the parent naproxen.

Docosahexaenoic Acid Modulates Paracellular Absorption of Testosterone and Claudin-1 Expression in a Tissue-Engineered Skin Model

Healthy skin moLEdels produced by tissue-engineering often present a suboptimal skin barrier function as compared with normal human skin. Moreover, skin substitutes reconstructed according to the self-assembly method were found to be deficient in polyunsaturated fatty acids (PUFAs). Therefore, in this study, we investigated the effects of a supplementation of the culture media with docosahexaenoic acid (DHA) on the barrier function of skin substitutes. To this end, 10 μM DHA-supplemented skin substitutes were produced (n = 3), analyzed, and compared with controls (substitutes without supplementation). A Franz cell diffusion system, followed by ultra-performance liquid chromatography, was used to perform a skin permeability to testosterone assay. We then used gas chromatography to quantify the PUFAs found in the epidermal phospholipid fraction of the skin substitutes, which showed successful DHA incorporation. The permeability to testosterone was decreased following DHA supplementation and the lipid profile was improved. Differences in the expression of the tight junction (TJ) proteins claudin-1, claudin-4, occludin, and TJ protein-1 were observed, principally a significant increase in claudin-1 expression, which was furthermore confirmed by Western blot analyses. In conclusion, these results confirm that the DHA supplementation of cell culture media modulates different aspects of skin barrier function in vitro and reflects the importance of n-3 PUFAs regarding the lipid metabolism in keratinocytes.