Microemulsions (ME) have gained attention as an alternative pharmaceutical formulation for transdermal delivery systems. However, the complicated relationships between various ME compositions (causal ...factors) and their characteristics (response variable) have not been fully comprehended. To overcome this problem, the design and development of ME for transdermal delivery was performed in our study using Design Expert® Software. The model formulations of ME were prepared according to the ME region obtained from pseudo-ternary phase diagrams using the simplex lattice design as an optimization technique. In this study, ketoprofen-loaded ME composed of oleic acid, Cremophor® RH40, ethanol and water were prepared, and their characteristics (e.g., size, charge, conductivity, pH, viscosity, drug content, loading capacity and skin permeation flux) were evaluated. The ME having an appropriate skin permeation flux was used as the basis for optimization. The skin permeation flux of the experimental ME was very close to the flux predicted by Design Expert® Software and was significantly greater than that for the commercial product. Possible mechanisms for the enhancement of the skin permeation of the ME were also investigated using Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD). This finding provided an understanding of the relationship between the causal factors and response variables, as shown in the response surfaces. Moreover, these results indicated that the simple lattice design was beneficial for the pharmaceutical development of ME for transdermal delivery.
In the present study, novel ultradeformable liposomes (menthosomes; MTS), deformable liposomes (transfersomes; TFS) and conventional liposomes (CLP) were compared in their potential for transdermal ...delivery of meloxicam (MX). MTS, TFS and CLP were investigated for size, size distribution, zeta potential, elasticity, entrapment efficiency and stability. In vitro skin permeation using hairless mice skin was evaluated. Vesicular morphology was observed under freeze-fractured transmission electron microscopy (FF-TEM). Intrinsic thermal properties were performed using differential scanning calorimetry (DSC) and X-ray diffraction. The skin permeation mechanism was characterized using confocal laser scanning microscopy (CLSM). The results indicated that the difference in physicochemical characteristics of MTS, TFS and CLP affected the skin permeability. MTS and TFS showed higher flux of MX than CLP. CLSM image showed deformable vesicles mechanism for delivery of MX across the hairless mice skin. Our study suggested that ultradeformable and deformable liposomes (MTS and TFS) had a potential to use as transdermal drug delivery carriers for MX.
The effect of surface grafting with N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG2000-DSPE) onto three types of lipid nanocarriers, liposomes, ...niosomes and solid lipid nanoparticles (SLNs) on the skin penetration of sodium fluorescein (NaFI) was investigated. Confocal laser scanning microscopy (CLSM) was used to visualize the penetration pathways. Fourier transform infrared spectroscopy (FT-IR) was used to determine the skin hydration. The results showed that the physicochemical properties of each nanocarrier were modified after PEG grafting. In the skin penetration study, PEG grafting increased the flux of NaFI-loaded PEGylated liposomes and significantly decreased the flux of NaFI-loaded PEGylated niosomes and NaFI-loaded PEGylated SLNs. The skin deposition study and CLSM images showed that the intact liposome vesicles permeated into the skin. The niosomes and SLNs had little or no vesicles in the skin, suggesting that NaFI may have been released from these nanocarriers before permeation. Additionally, the fluorescent CLSM images of the SLNs showed that NaFI deposited along the length of hair follicles inside the skin, indicating that the skin penetration route may be through the transfollicular pathway. For the PEGylated nanocarriers, the PEGylated liposomes had higher fluorescence intensities than the non-PEGylated liposomes, indicating higher NaFI concentrations. The PEGylated niosomes and PEGylated SLNs had lower fluorescence intensities than those of the non-PEG modified niosomes and SLNs. For FT-IR results, PEGylated liposomes increased the skin hydration, while the grafting PEG onto niosomes and SLN surfaces decreased the skin hydration. This study showed that the surface grafting of PEG onto various nanocarriers affected the skin transport of NaFI.
The aim of this study is to develop meloxicam (MX)-loaded cationic transfersomes as skin delivery carriers and to investigate the influence of formulation factors such as cholesterol and cationic ...surfactants on the physicochemical properties of transfersomes (i.e., particle size, size distribution, droplet surface charge and morphology), entrapment efficiency, stability of formulations and
in vitro
skin permeation of MX. The transfersomes displayed a spherical structure. Their size, charge, and entrapment efficiency depended on the composition of cholesterol and cationic surfactants in the formulation. Transfersomes provided greater MX skin permeation than conventional liposomes and MX suspensions. The penetration-enhancing mechanism of skin permeation by the vesicles prepared in this study may be due to the vesicle adsorption to and/or fusion with the stratum corneum. Our results suggest that cationic transfersomes may be promising dermal delivery carriers of MX.
Boesenbergia rotunda (L.) Mansf contained a potent anti-obesity agent. The objectives of this study were to investigate the anti-adipogenesis and lipolysis effects of panduratin A from B. rotunda ...extract and develop extract-loaded lipolytic body microspicule (MS) serum. Panduratin A that was separated from the ethanolic extract of B. rotunda in fraction 3 (BP-3) were studied the bioactivity of 3T3-L1 preadipocyte cells. The extract-loaded MS serum was formulated and evaluated for safety and efficacy. The BP-3 extract containing panduratin A at 0.29 g per g of the extract was not toxic to the cells at concentrations lower than 10 µg/mL, and the antiadipogenesis and lipolysis effects of the BP-3 extract were strong at 10 µg/mL. To deliver bioactive panduratin A into and through the skin, MS serum was successfully formulated. Application of BP-3 extract-loaded MS serum to the human thigh for 14 d reduced the thigh circumference and increased skin hydration and firmness. Although the skin erythema was increased, no severe redness or pain was found. In conclusion, BP-3 extract acts as a potent bioactive compound to inhibit adipocyte cells, and the antiadipogenesis and lipolysis effects of BP-3 extract in MS serum might play an important role as a potential lipolytic body product for reducing human subcutaneous fat mass.
Major depressive disorder (MDD) is a silent global health problem that can lead to suicide. MDD development is suggested to result from numerous risk factors, including genetic factors. A precise ...tool for MDD diagnosis is currently not available. Recently, inflammatory processes have been identified as being strongly involved in MDD development and the reactivation of human herpesvirus type 6 (HHV-6), upregulating cytokines such as TNF-α, which are associated with MDD. Therefore, this study aimed to determine the association of HHV-6 with genetic factors, especially TNF-α mutation, in MDD patients and their relatives compared to healthy controls. The Patient Health Questionnaire (PHQ-9) was used to evaluate MDD status, and 471 oral buccal samples were investigated for HHV-6 infection and viral copy number by qPCR. TNF-α (-308G/A) gene mutation and the cytokines TNF-α, IL-6, and IL-10 were analyzed by high-resolution melting (HRM) analysis and enzyme-linked immunosorbent assay (ELISA). Whole-exome sequencing of buccal samples was performed to analyze for genetic factors. The results showed significantly higher HHV-6 positivities and viral loads in MDD patients (15/59 (25.67%) and 14,473 ± 16,948 copies/µL DNA) and their relatives (blood relatives 17/36 (47.22%) and 8146 ± 5656 copies/µL DNA); non-blood relatives 7/16 (43.75%) and 20,721 ± 12,458 copies/µL DNA) compared to the healthy population (51/360 (14.17%) and 6303 ± 5791 copies/µL DNA). The TNF-α (-308G/A) mutation showed no significant difference. Surprisingly, 12/26 (46.15%) participants with the TNF-α (-308G/A) mutation showed HHV-6 positivities at higher rates than those with wild-type TNF-α (-308G) (70/267 (26.22%)). HHV-6-positive participants with TNF-α (-308G/A) showed higher levels of TNF-α, IL-6, and IL-10 than those of negative control. Exome analysis revealed that common mutations in immune genes were associated with depression. Therefore, this study unveiled the novel association of inflammatory gene TNF-α (-308G/A) mutations with HHV-6 reactivation, which could represent a combined risk factor for MDD. This result could induce further research on MDD development and clinical applications.
The aim of this study was to develop novel microemulsions (MEs) for the transdermal delivery of capsaicin. Microemulsion-based nonionic surfactants consisting of isopropyl myristate as the oil phase, ...various nonionic surfactants as the surfactant (S), various glycols or alcohol as the co-surfactant (CoS), and reverse osmosis water as the aqueous phase were formulated. Based on the optimal ME obtained from Design Expert®, MEs containing a fixed concentration of oil, water or surfactant were prepared while varying the amounts of the other two fractions. The results indicated that the skin permeation flux of low dose capsaicin (0.15% (w/w)) was significantly higher for the selected ME than the commercial product and capsaicin in ethanol (control) by approximately two- and four-fold, respectively. We successfully demonstrated the feasibility of the transdermal delivery of capsaicin-loaded ME using a low concentration of nonionic surfactant and ethanol. Moreover, the optimization using computer program helped to simplify the development of a pharmaceutical product.
The objective of this study was to investigate the influence of surfactant charge, surfactant carbon chain length, and surfactant content on the physicochemical characteristics (ie, vesicle size, ...zeta potential, elasticity, and entrapment efficiency), morphology, stability, and in vitro skin permeability of meloxicam (MX)-loaded liposome. Moreover, the mechanism for the liposome-enhanced skin permeation of MX was determined by Fourier transform infrared spectroscopy and differential scanning calorimetry. The model formulation used in this study was obtained using a response surface method incorporating multivariate spline interpolation (RSM-S). Liposome formulations with varying surfactant charge (anionic, neutral, and cationic), surfactant carbon chain length (C4, C12, and C16), and surfactant content (10%, 20%, and 29%) were prepared. The formulation comprising 29% cationic surfactant with a C16 chain length was found to be the optimal liposome for the transdermal delivery of MX. The skin permeation flux of the optimal formulation was 2.69-fold higher than that of a conventional liposome formulation. Our study revealed that surfactants affected the physicochemical characteristics, stability, and skin permeability of MX-loaded liposomes. These findings provide important fundamental information for the development of liposomes as transdermal drug delivery systems.
Phusang warm pond or Phusang hot spring (Thailand) has a temperature of approximately 36–38 °C and may be suitable for bacterial growth. However, data on the microbiota and effectiveness of this ...water remain obscure. Therefore, this study aimed to evaluate the characteristics of Phusang hot spring water by clarifying the microorganisms and viral pathogens present. Cytotoxicity, irritation, liposome uptake, antimicrobial and anti-inflammatory effects were evaluated. The levels of trace elements such as sodium (Na), calcium (Ca), and strontium (Sr) were confirmed. Phusang hot spring water was nontoxic to L-929 cells and HDFa cells and was nonirritating to human phototypes I to IV at 48 h. The antimicrobial effects of Phusang hot spring water on S.aureus, S. epidermidis, B. subtilis and E. coli were not detected using the agar well diffusion assay. Phusang hot spring water decreased interleukin-6 (IL-6) expression at 24 h compared with (PBS) and untreated controls, as measured using semi qRT–PCR and ELISA. Phusang hot spring water combined with curcumin-loaded liposomes exerted antiaging effects, suggesting their benefits for application in cosmetic products. The bacteriophage families Myoviridae, Siphoviridae and Podoviridae were detected, but not HPV or EBV. Trace elements such as Na and Ca were present. Therefore, the importance of this study is that Phusang hot spring water exerts anti-inflammatory effects via IL-6, is nontoxic and nonirritating, and might be used for balneotherapy or as a cosmetic ingredient under sterile conditions.
Coronavirus disease (COVID-19) cases are continuing to rise around the world, with more than 607 million confirmed cases and more than 6.51 million deaths as of September 2022. The World Health ...Organization (WHO) has emphasized the importance of hygiene in the ongoing COVID-19 pandemic, especially in elderly and bedridden patients. The use of no-rinse shampoo represents a simple change in hair-cleansing products. Daily hospital hair washing for the elderly, bedridden, and ICU patients would be more readily adopted. The objective of this study was to design and optimize a new no-rinse shampoo based on electrochemically reduced water (ERW) using response surface methodology. The relationship between coconut-based surfactant mixtures in a no-rinse shampoo and the resulting physicochemical properties, effectiveness (antibacterial and antifungal activity), and stability of the shampoo was investigated. The vesicle size, size distribution, zeta potential, conductivity, pH, foamability, wetting time, turbidity, and stability of the model formulation were optimized. The optimal formulation with the appropriate physicochemical properties and stability was selected. The effectiveness of the optimal formulation was compared to that of commercially available products. The dry shampoo (DS4) containing 3.5% of the mixed detergent with ERW may prevent infection by Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans. The no-rinse shampoo based on ERW successfully demonstrated good stability in addition to efficacy in terms of antibacterial and antifungal activity. The treated hair fiber was not significantly different from that of the intact hair fiber. Under the scanning electron microscopy (SEM) and the atomic force microscopy (AFM), the cuticle layer of the treated hair fiber was not damaged. Thus, no-rinse shampoos may reduce the time of hair rinsing and improve the quality of life of caregivers.
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