Wood vinegar is well known as a softening agent affecting on the stratum corneum that is easy to penetrate into the skin. In this study, we prepared mixed ursolic acid hydrogel with wood vinegar(1, 2, 5%) as a penetration enhancer. The accumulation of ursolic acid in the skin from hydrogels was evaluated in vitro hairless mouse skin and skin moisturizing effect of them was evaluated using the corneometer and the tewermeter. And the role of stratum corneum as a protective barrier was evaluated as well. The hydrogels were retained about 40% of water retention capacity 2hrs and had better effect on the stripped skin than full-thickness skin. The accumulation of ursolic acid through stripped skin from hydrogels with wood vinegar was not change compared to normal skin, which indicated the action site of wood vinegar and the accumulation site of ursolic acid would be stratum corneum. From these result, we could find wood vinegar seems to be a good enhancer for active materials with anti-wrinkle and anti aging effect such as ursolic acid, and can be a developed topical delivery system maintaining excellent water retention capacity.
Proliposomal patch of clenbuterol, ${\beta}_2-agonist$ bronchodilator, was prepared and its feasibility as a novel transdermal drug delivery system was examined. Proliposomal granules containing clenbuterol was prepared by a standard method using sorbitol and lecithin with (Rx 2) or without cholesterol (Rx 1). The porous structure of sorbitol in the proliposomes was maintained allowing tree flowability of the granules. Following contact with water, the granules were converted probably to liposomes almost completely within several minutes. It indicates that proliposomes may be hydrated, when they are applied on the skin under occlusive condition in vivo, by the sweat to form liposomes. Clenbuterol release from Rx 1 and Rx 2 proliposomes to pH 7.4 isotonic phospate buffer (PBS) across cellulose membrane (mol. wt. cut-off of 12000-14000) was retarded significantly compared with that from the mixture of clenbuterol powder and blank proliposomes. Interestingly, proliposomes prepared with lecithin and cholesterol (i.e., Rx 2 proliposomes) showed much more retarded release of clenbuterol than proliposomes prepared only with lecithin (i.e.. Rx 1 proliposomes), indicating that clenbuterol release from proliposomes can be controlled by the addition of cholesterol to the proliposomes. Proliposomal patches were prepared using PVC film as an occlusive backing sheet, two sides adhesive tape (urethane, 1.45 mm thickness) as a reservoir for proliposome granules and Millipore MF-membrane (0.45 mm pore size) as a drug release-controlling membrane. Rx 1 or Rx 2 proliposomes containing 4.6 mg of clenbuterol were loaded into the reservoir of the patch. Clenbuterol release from the patches to pH 7.4 PBS was determined using USP paddle (50 rpm)-over-disc release method. Clenbuterol release from the proliposomal patches was much more retarded even than from a matrix type clenbuterol patch (Boehringer Ingelheim ltd). Being consistent with clenbuterol release from the proliposomal granules, the release from the patches was highly dependent on the presence of cholesterol in the proliposomes : Patches containing Rx 2 proliposomes showed several fold slower drug release than patches containing Rx 1 proliposomes. When the patch containing Rx 1 proliposomes was applied on to the back of a hair-removed rat, clenbuterol concentration in the rat blood was maintained during 6-72 hrs. Transdermal absorption of clenbuterol from the patch was accelerated when the patch was prehydrated with 50 ml of pH 7.4 PBS before topical application. Above results indicate that sustained transdermal delivery of clenbuterol is feasible using proliposomal patches if the cholesterol content and pore size of the release rate-controlling membrane of patches, for example, are appropriately controlled.
Journal of the korean academy of Pediatric Dentistry
/
v.26
no.2
/
pp.262-274
/
1999
Several alternatives for increasing the fluoride concentration in the mouth, such as water fluoridation, ingestion of fluoride supplements, fluoride paste, fluoride mouthrinse, application of fluoride gel are available. There is an impressive body of evidence that the topically deliverd fluorides are clinically effective in inhibiting the progression of dental caries. Recent studies on the cariostatic action of fluoride have indicated the importance of fluoride in the fluid environment of the teeth. The fluoride levels in unstimulated whole saliva can be considered indicative of F in the aqueous phase available for interaction with the tooth surface at a given time. The retention of F in the mouth after topical fluoride treatment is considered to be an important factor in the clinical efficacy of F. The aim of this study was to determine the elevation and clearance of fluoride in whole saliv after the following topical flouride treatments using HMDS-diffusion technique and fluoride ion electrode. The obtained results were as follow: 1. Average salivary fluoride concentration in the unstimulated whole saliva was $0.0152ppm{\pm}0.0091ppm$. Unstimulated salivary flow rate was between 0.34-0.36ml/min and there was no statistically significant difference among the groups(p>0.05). 2. Except for the immediate time after treatment, fluoride levels followed as APF gel>neutral gel>F-rinse>F-paste. There was no statistical difference between the salivary F concentration of F-paste group and that of control group after 2 hours. In case of F-rinse group, after 3 hours the concentration had dropped to baseline value. But there was statistically significant difference among the F concentraion of F gel groups and that of control group(p<0.05). 3. The mean $AUC_{0-120min}$ values were followed as neutral gel>APF gel>F-rinse>F-paste, and the values of the two former groups were significantly higher than those of the two latter groups(p<0.05).
Kim, Tae-Hwan;Kwak, Myung-Ho;Lee, Choon-Ho;Park, Jun-Woo;Park, Young-Wook;Kim, Seong-Gon
Maxillofacial Plastic and Reconstructive Surgery
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v.31
no.3
/
pp.193-197
/
2009
Background: Though it is clear that many types of viruses can infect the oral mucosa, its condition for infection is unclear. The purpose of this study was to analyze the conditions for viral infection of normal oral mucosa and explore the possibility of topical gene therapy to oral mucosa using a viral vector. Methods: Freshly taken fragments of the palate and the tongue of mice were used for organ culture. The specimens were exposed to green fluorescent protein (GFP)-adenoviral vector for 1 hour except for the control. Initial viral titer was $6.3{\times}10^{11}\;pfu/ml$ and the virus was diluted to working concentrations. The dilution ratio was 1:1,000 ($6.3{\times}10^8\;pfu/ml$), 1:10,000 ($6.3{\times}10^7\;pfu/ml$), and 1:100,000 ($6.3{\times}10^6\;pfu/ml$). They were then cultured on a stainless steel wire mesh in an organ culture dish. The specimens were stereoscopically examined every 24 hours for 6 days, after which they were fixed and analyzed through immunohistochemical methods Results: There was no visible expression in the control, $6.3{\times}10^6\;pfu/ml$, and $6.3{\times}10^7\;pfu/ml$ groups. Initial expression was observed at 24 hours after infection in both the palate and the tongue in $6.3{\times}10^8\;pfu/ml$ and the expression significantly increased until 3 days in the palate and 2 days in the tongue after infection (P<0.05). In both groups, the expression was mostly observed at the resection margin. Immunohistochemical studies showed that the epithelial cells were positive to GFP. Conclusion: The present study showed that topically applied adenovirus containing specific genetic information of GFP could successfully transduce GFP in normal oral epithelial cells at the resection margin in organ culture in terms of dose and exposure time.
Lee Geun-Soo;Kim Tae-Hoon;Lee Chun-Il;Pyo Hyeong-Bae;Choe Tae-Boo
Journal of the Society of Cosmetic Scientists of Korea
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v.31
no.2
s.51
/
pp.141-146
/
2005
Unstable cosmetic active ingredients could rapidly break down in chemical and photochemical process. Therefore, it has become a very important issue to encapsulate active ingredient for the stabilization. 7-Dehydrocholesterol (7-DHC), a precursor of vitamin $D_3$, has been shown to increase levels of protein and mRNA for heat shock protein in normal human epidermal keratinocytes. However, topical dermal application of 7-DHC is restricted due to its poor solubility and chemical unstability. In this study, 7-DHC was incorporated into nano-emulsion (NE), solid lipid nano-particle (SLN), and chitosan coated solid lipid nano-particle (CASLN), respectively. In order to prepare NE and SLN dispersion, high-pressure homogenization at temperature above the melting point of lipid was used Hydrogenated lecithin and polysorbate 60 were used as stabilizer for NE and SLN. CASLN was prepared by high speed homogenizing after adding chitosan solution to the SLN dispersion and showed positively charged particle properties. Decomposition rate of 7-DHC in NE, SLN and CASLN was studied as a function of time at different temperature. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies were performed to characterize state of lipid modification. It appeared that CASLN is the most effective to stabilize 7-DHC and may be used for a useful topical dermal delivery system.
Angelica gigas Nakai (AGN) has been used in Korean herbal medicine for various pharmacological activities, such as to create antioxidant and skin whitening effects. Decursin and decursinol angelate of AGN extracts can be used as potential active drugs and cosmetic ingredients. This study investigated the possibility of topical delivery of AGN extracts using a manufactured emulsion system. Lotion was formulated by using Tefose® and paraffin for the oil phase, Kolliphor RH 40 for the surfactant and solubilizing agent-which showed high solubility in water (0.82 mg/ml)-and a water phase with a carbomer. In vitro skin permeation of decursin and decursinol angelate was determined using a Strat-M® membrane in Franz diffusion cells. Lotion samples as the experimental group (248.08±19.72 ug/cm2) significantly increased the permeation of decursin and decursinol angelate for up to 24 hr compared to the control group (119.18±19.23 ug/cm2). The permeability was also characterized by the flux (penetration rates) and Kp (permeability coefficient) values. The experimental group (17.20±1.23 ug/h/cm2 and 5.73±1.39 cm/h*10-3) had higher flux and Kp than the control group (8.22±1.24 ug/h/cm2 and 2.74±0.51 cm/h*10-3). Lotion with decursin and decursinol angelate of AGN extracts could be used for the topical application of drug and cosmetic products.
Kim, Ki Taek;Kim, Ji Su;Kim, Min-Hwan;Park, Ju-Hwan;Lee, Jae-Young;Lee, WooIn;Min, Kyung Kuk;Song, Min Gyu;Choi, Choon-Young;Kim, Won-Serk;Oh, Hee Kyung;Kim, Dae-Duk
Biomolecules & Therapeutics
/
v.25
no.4
/
pp.434-440
/
2017
S-methyl-$\small{L}$-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.
Methyl methacrylate-butyl methacrylate copolymer (MMBM)-dibutyl phthalate (DBP) films were investigated as a potential topical drug delivery system for the controlled release of nitrofurazone. The kinetic analysis of release data indicated that drug release followed a diffusion-controlled granular matrix model, where the quantity released per unit area is proportional to the square root of time. DBP of several hydrophobic plasticizers selected was found to give the highest release of nitrofurazone. However, hydrophilic plasticizers such as propylene glycol and polyethylene glycol 400 had no controlled release properties and acceptable film formation. The effects of changes in film composition, drug concentration, film thickness, pH of release medium, and temperature on the in vitro release of nitrofurazone were analyzed both theoretically and experimentally. The release rate constant (k') was found to be proportional to DBP content, pH, and the temperature of release medium, but independent of film thickness, and drug concentration in a range of 0.1-0.4% by weight. The linear relationship was found to exist between the log k' and DBP content. The release of nitrofurazone from MMBM-DBP (8:2) films was found to be an energy-linked process. Two energy terms were calculated ; the activation energy for matrix diffusion was 13.45 kcal/mole, and the heat of drug crystal solvation was 27.26-29.34 kcal/mole. Observation of scanning electron micrographs and microscopic photographs showed that the incorporation of DBP in films increased markedly the particle size of nitrofurazone dispersed in the film matrix, comparing with the fine dispersion of nitrofurazone in pure MMBM film alone.
Lee, Su Jin;Kim, Jung A;Kang, Nae Gyu;Park, Sun Gyoo;Lee, Cheon Koo
Journal of the Society of Cosmetic Scientists of Korea
/
v.41
no.3
/
pp.201-208
/
2015
Organogels are semi-solid systems that consist of an apolar solvent as the liquid phase within a three-dimensional networked structure. In this study, we developed a stable and skin penetration-enhanced Lecithin Organogel (LO) containing genistein, which is one of the poorly soluble active ingredients in both polar and apolar phase. After screening of various components (type of gelators, organic and aqueous phase), hydrogenated lecithin (HL), sunflower oil (SO), dipropylene glycol (DPG), and polyethylene glycol (PEG) were mainly used in this formulation. Phase ternary diagram was employed for optimization of the composition in the LO. The formulated LO were evaluated for its organoleptic characteristics, stability, pH, rheology, phase transition temperatures, microscopic analysis and skin penetration. The optimized stable LO system can be utilized as an effective and stable cosmetic formulation that can carry poorly soluble active ingredients at high concentration for topical dermal delivery.
External lyogels containing prostaglandin $E_1$ ethyl ester $(PGE_1-EE)$, a prodrug of prostaglandin $E_1\;(PGE_1)$ as a therapeutic agent for erectile dysfunction, were formulated to overcome the aqueous instability and enhance the percutaneous absorption. Lyogels of $PGE_1-EE$ were prepared with ethanol (EtOH)/proplyene glycol (PG) cosolvent system as a vehicle, cineol as an enhancer, and hydroxypropylcellusose as a gelling agent. In vitro percutaneous absorption studies were performed to determine the rate of $PGE_1$ absorption through rat or hairless mouse skin. The permeability of $PGE_1-EE$ lyogel with enhancer was 16-fold greater than that of lyogel without enhancer. Cosolvent produced 9-fold increase in percutaneous absorption. Pharmacodynamic effects of lyogels were evaluated in mature male cats in terms of intracavernosal pressure (ICP). Lyogels containing 0.1 % of $PGE_1-EE$ showed higher ICP compared to intraurethral preparation of $PGE_1$ (1 %) and enhancer-free control lyogel. The shelf-life $(t_{10%})$ of lyogel at refrigerated condition $(4^{\circ}C)$ was calculated as 928 days, which is 4.2 times longer than that of control hydrogel. As a result, $PGE_1-EE$ was formulated successfully to a lyogel system with a selective enhancer and cosolvent system for the topical delivery of $PGE_1$.
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