Search Results (216)

Due to the rapid increase in the use of anti-aging cosmetic products, there is a need to develop valid analytical methods to control their quality. The present work deals with the development and validation of a new chromatographic method for the quantitative determination of five lipophilic components (resveratrol, ferulic acid, quercetin, retinol, and α-tocopherol), with anti-aging properties, in a cold cream (w/o). For the HPLC-UV separation of the active ingredients, an HS, Discovery^® Supelco (Supelco Inc., Bellefonte, PA, USA), C₁₈ column (25 cm × 4.6 mm), 5 μm (at 40 °C) was used as a stationary phase while a binary system of A: Acetonitrile with formic acid 0.2% and B: H₂O with formic acid 0.2%, in gradient elution (flow 1.5 mL·min⁻¹), was used as mobile. The analytical method was validated according to ICH guidelines Q2(R2), where linearity (r² ≥ 0.998), selectivity, precision (% recovery 97.1–101.9), and accuracy (%RSD < 2) were evaluated. The processing of the samples for the recovery of the five analytes from the cream was investigated by experimental design methodology and the cross D-optimal technique (% recovery 98.5–102.9, %RSD < 2%, n = 5). Finally, the same analysis was applied to study the transdermal penetration of the active ingredients incorporated in cold cream (over a period of 8 h). Their behavior was compared with the corresponding one in suspension using Franz cells in a vertical arrangement. The new method is considered reliable for the analysis of the anti-aging product. Full article

Background/Objectives: Cyclovirobuxine D, a natural compound derived from the medicinal plant Buxus sinica, demonstrates a diverse array of therapeutic benefits, encompassing anti-arrhythmic properties, blood pressure regulation, neuronal protection, and anti-ischemic activity. However, its limited solubility hinders the bioavailability of current oral and injectable formulations, causing considerable adverse reactions and toxicity. Methods: In this investigation, we embarked on an unprecedented exploration of the skin penetration potential of cyclovirobuxine D utilizing chemical penetration enhancers and niosomes as innovative strategies to enhance its dermal absorption. These strategies were rigorously tested and optimized. Results: Among the tested chemical penetration enhancers, azone emerged as the most potent, achieving a 4.55-fold increase in skin penetration compared to the untreated group. Additionally, when encapsulated within niosomes, primarily composed of Span60 and cholesterol, the skin penetration of cyclovirobuxine D was notably enhanced by 1.50-fold. Furthermore, when both cyclovirobuxine D and azone were co-encapsulated within the niosomes, the skin penetration of cyclovirobuxine D was remarkably elevated by 8.10-fold compared to the solvent-dispersed group. This enhancement was corroborated through rigorous in vitro and in vivo experiments. Notably, the combination of other chemical penetration enhancers with niosome encapsulation also exhibited synergistic effects in enhancing the skin penetration of cyclovirobuxine D. Conclusions: These findings provide a compelling rationale for the administration of cyclovirobuxine D via skin-mediated transdermal delivery, offering superior safety, efficacy, and convenience. The innovative combination of niosomes and chemical penetration enhancers represents a novel system for the transdermal delivery of cyclovirobuxine D, holding immense promise for clinical applications in the treatment of brain, neuronal, and cardiovascular disorders. Full article

Microneedles (MNs), composed of multiple micron-scale needle-like structures attached to a base, offer a minimally invasive approach for transdermal drug delivery by penetrating the stratum corneum and delivering therapeutic agents directly to the epidermis or dermis. Hydrogel microneedles (HMNs) stand out among various MN types due to their excellent biocompatibility, high drug-loading capacity, and tunable drug-release properties. This review systematically examines the matrix materials and fabrication methods of HMN systems, highlighting advancements in natural and synthetic polymers, and explores their applications in treating conditions such as wound healing, hair loss, cardiovascular diseases, and cancer. Furthermore, the potential of HMNs for disease diagnostics is discussed. The review identifies key challenges, including limited mechanical strength, drug-loading efficiency, and lack of standardization, while proposing strategies to overcome these issues. With the integration of intelligent design and enhanced control over drug dosage and safety, HMNs are poised to revolutionize transdermal drug delivery and expand their applications in personalized medicine. Full article

Sinomenine (SIN) is a drug for the treatment of rheumatoid arthritis, most of which is administered orally, but it is prone to adverse gastrointestinal effects. Gel can overcome the gastrointestinal adverse effects caused by oral administration. In this paper, a multiscale computational pharmaceutics strategy was developed to guide the systematic study of formulation factors of a SIN gel and, further, to guide the formulation design. A molecular dynamics (MD) simulations method was utilized to successfully screen the optimal prescription of SIN gel and to elucidate the molecular mechanisms affecting the quality of SIN gel. The optimal prescription was 3.0% of SIN, 1.0% of Carbopol (Cp), 30% of Ethanol (Eth), 5.0% of Glycerine (Gly) and 10.0% of Menthol (Men). The influence mechanism can be explained by the combination of multiple parameters, such as the microstructure diagram, the radius of gyration (Rg) and the radial distribution function (RDF). In vitro transdermal studies were carried out using a modified Franz diffusion cell method to evaluate the quality of the screened and reference prescriptions. The results showed that the cumulative penetration and penetration rate of the screening of prescription were better than the reference formulation. Most important of all, the simulation results are in good agreement with the in vitro release experiment, indicating that the strategy has good applicability. This study was able to accurately optimize the formulation and elucidate the molecular mechanism, which would provide a reference for further research on SIN and gel. Full article

Background/Objectives: Indomethacin (IDM) is commonly used to treat chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis. However, long-term oral IDM treatment can harm the gastrointestinal tract. This study presents a design for encapsulating IDM within mixed micelles (MMs)-loaded dissolving microneedles (DMNs) to improve and sustain transdermal drug delivery. Methods: Indomethacin-loaded mixed micelles (IDM-MMs) were prepared from Soluplus^® and Poloxamer F127 by means of a thin-film hydration method. The MMs-loaded DMNs were fabricated using a two-step molding method and evaluated for storage stability, insertion ability, in vitro release, in vitro transdermal penetration, and in vivo PK/PD studies. Results: The obtained MMs were stable at 4 °C and 30 °C for 60 days. The in vitro IDM transdermal penetration was remarkably improved by the MMs-loaded DMNs compared to a commercial patch. A pharmacokinetic study demonstrated that the MMs-loaded DMNs had a relative bioavailability of 4.1 in comparison with the commercial patch. Furthermore, the MMs-loaded DMNs showed a significantly shorter lag time than the commercial patch, as well as a more stable plasma concentration than the DMNs without MMs. The therapeutic efficacy of the IDM DMNs was examined in Complete Freund’s Adjuvant-induced arthritis mice. The IDM DMN treatment effectively reduced arthritis severity, resulting in decreased paw swelling, arthritis index, spleen hyperplasia, and serum IL-1β and TNF-α levels. Conclusions: Our findings demonstrated that the novel MMs-loaded DMNs were an effective strategy for sustained IDM release, providing an alternate route of anti-inflammatory drug delivery. Full article

Skin diseases are a common health problem affecting millions of people worldwide. Effective treatment often depends on the precise delivery of drugs to the affected areas. One promising approach is currently the transdermal drug delivery system (TDDS), whose significant challenge is the poor penetration of many compounds into the skin due to the stratum corneum (SC), which acts as a formidable barrier. To overcome this limitation, nanocarriers have emerged as a highly effective alternative. This review discusses the use of liposomes and ethosomes for transdermal drug delivery. Liposomes are micro- or nanostructures consisting of a lipid bilayer surrounding an aqueous core. They facilitate transdermal drug penetration and may be advantageous for site-specific targeting. Some methods of treating skin diseases involve incorporating drugs such as acyclovir, dithranol, and tretinoin or bioactive compounds such as fluconazole, melanin, glycolic acid, kojic acid, and CoQ10 into nanocarriers. The inability of liposomes to pass through the narrowed intercellular channels of the stratum corneum led to the invention of lipid-based vesicular systems such as ethosomes. They are structurally similar to conventional liposomes, as they are prepared from phospholipids, but they contain a high ethanol concentration. Ethosomes are noninvasive carriers that allow drugs to reach the deep layers of the skin. Examples of commonly used substances and drugs combined with ethosomes in cosmetics include methotrexate, ascorbic acid, vitamin A and E, and colchicine. A significant development in this area is the use of rutin-loaded ethosomes. Encapsulating rutin in ethosomes significantly improves its stability and enhances skin penetration, allowing more efficient delivery to deeper skin layers. In cosmetics, rutin–ethosome formulations are used to protect the skin from oxidative stress, reduce redness, and improve capillary strength, making it a valuable formulation in anti-aging and anti-inflammatory products. The results of the first clinical trial of the acyclovir–ethosome formulation confirm that ethosomes require further investigation. The work provides an update on recent advances in pharmaceutical and cosmetic applications, mentioning the essential points of commercially available formulations, clinical trials, and patents in the recent past. Full article

Several industries are increasingly focused on enhancing the delivery of active ingredients through the skin to optimize therapeutic outcomes. By facilitating the penetration of active ingredients through the skin barrier, these enhancers can significantly improve the efficacy of various formulations, ranging from skincare products to therapeutic agents targeting systemic circulation. As the understanding of skin physiology and the mechanisms of drug absorption deepen, these industries are adopting permeation enhancers more widely, ultimately leading to better patient outcomes and expanded treatment options. However, the structure and physiological function of the skin can vary according to different factors, such as the area of the body and between individuals. These variations, along with external environmental exposures, aging and pathological conditions, introduce complexities that must be carefully considered when designing effective delivery systems. Considering the intricacies of skin structure and physiology, tailoring systems to account for regional differences, individual variability, and changes induced by environmental factors or disease is critical to optimizing therapeutic outcomes. This review discusses the features of skin structure, physiology, and pathologies, as well as the application of permeation enhancers in these contexts. Furthermore, it addresses the use of animal skin models in transdermal delivery and dermatological studies, along with the latest developments in this field. Full article

Dermatoses are among the most prevalent non-fatal conditions worldwide. Given this context, it is imperative to introduce safe and effective dermatological treatments to address the diverse needs and concerns of individuals. Transdermal delivery technology offers a promising alternative compared to traditional administration methods such as oral or injection routes. Therefore, this review focuses on the recent achievements of nanocarrier-based transdermal delivery technology for dermatological therapy, which summarizes diverse delivery strategies to enhance skin penetration using various nanocarriers including vesicular nanocarriers, lipid-based nanocarriers, emulsion-based nanocarriers, and polymeric nanocarrier according to the pathogenesis of common dermatoses. The fundamentals of transdermal delivery including skin physiology structure and routes of penetration are introduced. Moreover, mechanisms to enhance skin penetration due to the utilization of nanocarriers such as skin hydration, system deformability, disruption of the stratum corneum, surface charge, and tunable particle size are outlined as well. Full article

Transdermal drug delivery systems (TDDSs) are designed to administer a consistent and effective dose of an active pharmaceutical ingredient (API) through the patient’s skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. The API provides the continuous and prolonged administration of a substance at a consistent rate. TDDSs, or transdermal drug delivery systems, have gained significant attention as a non-invasive method of administering APIs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome the bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. A TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first pass metabolism, as well as the corrosive acidic environment of the stomach, that happens when drugs are taken orally. Various approaches have been developed to enhance the transdermal permeability of different medicinal compounds. Recent improvements in TDDSs have enabled the accurate administration of APIs to their target sites by enhancing their penetration through the stratum corneum (SC), hence boosting the bioavailability of drugs throughout the body. Popular physical penetration augmentation methods covered in this review article include thermophoresis, iontophoresis, magnetophoresis, sonophoresis, needle-free injections, and microneedles. This review seeks to provide a concise overview of several methods employed in the production of TDDSs, as well as their evaluation, therapeutic uses, clinical considerations, and the current advancements intended to enhance the transdermal administration of drugs. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient TDDSs. Full article

Objectives: To address the poor efficacy and percutaneous penetration of grape seed oil, ionic liquids and nanotechnology were combined to prepare a grape seed oil emulsion. Methods: A novel Menthol-CoQ10 ionic liquid and ionic liquid based grapeseed oil emulsion were prepared and confirmed. Results: The average size of the grapeseed oil emulsion was 218 nm, and its zeta potential was −33.5 mV. The ionic liquid-based grape seed oil emulsion exhibited a transdermal penetration effect 4.63-fold higher than that of ordinary grape seed oil emulsion. Ionic liquid also displayed enhanced efficiency both in vitro and in vivo. It significantly inhibited the production of DPPH free radicals and tyrosinase, inhibited melanin and matrix metalloproteinase-1 (MMP-1) produced by cells, and promoted type I collagen expression in fibroblasts. After 28 days of continuous use, the grapeseed oil emulsion improved the water content of the stratum corneum and the rate of transepidermal water loss, enhanced the firmness and elasticity of the skin, and significantly improved the total number and length of under-eye lines, tail lines, nasolabial folds, and marionette lines on the face. Conclusions: Menthol-CoQ10 ionic liquid is a promising functional excipient for both transdermal delivery increase and efficient enhancement. Ionic liquid and nanotechnology for grape seed oil facial mask displayed significantly enhanced efficacy and permeability. Full article

Skin and soft-tissue infections require significant consideration because of their prolonged treatment duration and propensity to rapidly progress, resulting in severe complications. The primary challenge in their treatment stems from the involvement of drug-resistant microorganisms that can form impermeable biofilms, as well as the possibility of infection extending deep into tissues, thereby complicating drug delivery. Dissolving microneedle patches are an innovative transdermal drug-delivery system that effectively enhances drug penetration through the stratum corneum barrier, thereby increasing drug concentration at the site of infection. They offer highly efficient, safe, and patient-friendly alternatives to conventional topical formulations. This comprehensive review focuses on recent advances and emerging trends in dissolving-microneedle technology for antimicrobial skin-infection therapy. Conventional antibiotic microneedles are compared with those based on emerging antimicrobial agents, such as quorum-sensing inhibitors, antimicrobial peptides, and antimicrobial-matrix materials. The review also highlights the potential of innovative microneedles incorporating chemodynamic, nanoenzyme antimicrobial, photodynamic, and photothermal antibacterial therapies. This review explores the advantages of various antimicrobial therapies and emphasizes the potential of their combined application to improve the efficacy of microneedles. Finally, this review analyzes the druggability of different antimicrobial microneedles and discusses possible future developments. Full article

Known for its stimulating effects on the nervous and cardiovascular systems, caffeine has proven remarkable versatile properties. It can be used in a wide range of different products, from anti-aging cosmetics to the pharmaceutical treatment of hair loss. Caffeine is known for its antioxidant properties and is commonly found in moisturising creams recommended as anti-aging or anti-cellulite and also for the treatment of different skin disorders, including androgenic alopecia. This bioactive is also described to be able to enhance the sunscreen scattering effect of well-known ultraviolet (UV) blockers. One of the major challenges remains its penetration capacity into deeper skin layers, which may be achieved by the use of nanosized delivery systems, yet without the risk of transdermal delivery. In this review, we discuss the nutraceutical value of caffeine in cosmetic products, so-called nutricosmetics, which grants this bioactive several advantages in several formulations, in comparison to other potential bioactives of nutricosmetic value. Furthermore, the disclosed effects of bioactives commonly found in coffee, tea, and their by-products are reviewed and discussed. The discussion concludes by highlighting the significant benefits of caffeine in the treatment of skin disorders and its potential to enhance and promote skin health. Full article

HxTx-Hv1h, a neurotoxic peptide derived from spider venom, has been developed for use in commercial biopesticide formulations. Cell Penetrating Peptides (CPPs) are short peptides that facilitate the translocation of various biomolecules across cellular membranes. Here, we evaluated the aphidicidal efficacy of a conjugated peptide, HxTx-Hv1h/CPP-1838, created by fusing HxTx-Hv1h with CPP-1838. Additionally, we aimed to establish a robust recombinant expression system for HxTx-Hv1h/CPP-1838. We successfully achieved the secretory production of HxTx-Hv1h, its fusion with Galanthus nivalis agglutinin (GNA) forming HxTx-Hv1h/GNA and HxTx-Hv1h/CPP-1838 in yeast. Purified HxTx-Hv1h exhibited contact toxicity against Megoura crassicauda, with a 48 h median lethal concentration (LC₅₀) of 860.5 μg/mL. Fusion with GNA or CPP-1838 significantly enhanced its aphidicidal potency, reducing the LC₅₀ to 683.5 μg/mL and 465.2 μg/mL, respectively. The aphidicidal efficacy was further improved with the addition of surfactant, decreasing the LC₅₀ of HxTx-Hv1h/CPP-1838 to 66.7 μg/mL—over four times lower compared to HxTx-Hv1h alone. Furthermore, we engineered HxTx-Hv1h/CPP-1838 multi-copy expression vectors utilizing the BglBrick assembly method and achieved high-level recombinant production in laboratory-scale fermentation. This study is the first to document a CPP fusion strategy that enhances the transdermal aphidicidal activity of a natural toxin like HxTx-Hv1h and opens up the possibility of exploring the recombinant production of HxTx-Hv1h/CPP-1838 for potential applications. Full article

Compared to other forms of drug administration, the use of Transdermal Drug Delivery Systems (TDDSs) offers significant advantages, including uniform drug release profiles that contribute to lower side effects and higher tolerability, avoidance of direct exposure to the gastrointestinal tract, better patient compliance due to their non-invasive means of application and others. Mesoporous silica membranes are of particular interest in this regard, due to their chemical stability and their tunable porous system, with adjustable pore sizes, pore volumes and surface chemistries. While this allows for fine-tuning and, thus, the development of optimized TDDSs with high loading capacities and the desired release profile of a given drug, its systemic availability also relies on skin penetration. In this paper, using a TDDS based on mesoporous silica membranes in Franz cell experiments on porcine skin, we demonstrate surprisingly substantial drug loss during skin penetration. Drug passage through porcine skin was found to be dependent on the age and pre-treatment of the skin. pH and temperature were major determinants of drug recovery rates as well, indicating drug loss in the skin by enzymatic metabolization. Regarding the TDDS, higher loading obtained by SO₃H surface modification of the mesoporous silica membranes reduced drug loss. Still, high loss rates in the skin were determined for different drugs, including anastrozole, xylazine and imiquimod. We conclude that, beyond the fine-tuned drug release profiles from the mesoporous silica membrane TDDS, remarkably high drug loss in the skin is a major issue for achieving desired skin penetration and, thus, the systemic availability of drugs. This also poses critical requirements for defining an optimal TDDS based on mesoporous silica membranes. Full article

Background: Terbinafine hydrochloride (TEB) is a broad-spectrum antifungal medication commonly used to treat fungal infections of the skin. This study designed a hydrogel patch assisted by an iontophoresis system to enhance the transdermal permeability of TEB, enabling deeper penetration into the skin layers. Methods: The influences of current intensity, pH levels, and drug concentration on the TEB hydrogel patch’s permeability were explored using an adaptive ion electroosmosis system. The pharmacokinetic profile, facilitated by iontophoresis for transdermal permeation, was analyzed through the application of microdialysis technology. Scanning electron microscopy and transmission electron microscopy were employed to assess the impact of ion electroosmotic systems on skin integrity. Results: The cumulative drug accumulation within 8 h of the TEB hydrogel patches, assisted by iontophoresis, was 2.9 and 7.9 times higher than without iontophoresis assistance and TEB cream in the control group, respectively. TEB hydrogel patches assisted by iontophoresis can significantly increase the permeability of TEB, and the AUC_{(0–8 h)} was 3.4 and 5.4 times higher, while the C_max was 4.2 and 7.3 times higher than the TEB hydrogel patches without iontophoresis, respectively. This system has no significant impact on deep-layer cells. Conclusions: This system may offer a safe and effective clinical strategy for the local treatment of deep antifungal infections. Full article