The feasibility of skin penetration was studied for aspalatone (AM, acetylsalicylic acid maltol ester), a novel antithrombotic agent. In this studys hairless mouse dorsal skins were used as a model to select composition of vehicle and AM. Based on measurements of solubility and partition coefficient, the concentration of PC that showed the highest flux for AM across the hairless mouse skin was found to be 40%. The cumulative amount permeated at 48 h, however, appear inadequate, even when the PC concentration was employed. To identify a suitable absorption enhancer and its optimal concentration for AM, a number of absorption enhancers and a variety of concentration were screened for the increase in transdermal flux of AM. Amongst these, linoleic acid (LOA) at the concentration of 5% was found to have the largest enhancement factor (i.e., 132). However, a further increase in AM flux was not found in the fatty acid concentration greater than 5%, indicating the enhancement effect is in a bell-shaped currie. In a study of the effect of AM concentration on the permeation, there was no difference in the permeation rate between 0.5 and 1% for AM, below its saturated concentration. At the donor concentration of 2%, over the saturated condition, the flux of AM was markedly increased. A considerable degradation of AM was found during permeation studies, and the extent was correlated with protein concentrations in the epidermal and serosal extracts, and skin homogenates. In rat dorsal skins, the protein concentration decreased in the rank order of skin homogenate > serosal extract > epidermal extract. Estimated first order degradation rate constants were $6.15{\pm}0.14,{\;}0.57{\pm}0.02{\;}and{\;}0.011{\pm}{\;}0.004{\;}h^{-1}$ for skin homogenate, serosal extract and epidermal extract, respectively. Therefore, it appeared that AM was hydrolyzed to some extent into salicylmaltol by esterases in the dermal and subcutaneous tissues of skin. taken together, our data indicated that transdermal delivery of AM is feasible when the combination of PC and LOA is used as a vehicle. However, since AM is not metabolically stable, acceptable degradation inhibitors may be nervessary to fully realize the transdermal delivery of the drug.
Journal of the Korean Applied Science and Technology
/
v.37
no.6
/
pp.1738-1751
/
2020
The skin is divided into three parts: the epidermis, the dermis, and the subcutaneous fat, and the stratum corneum, which is located at the top of the epidermis, acts as a barrier that prevents drug delivery. Nanoemulsions are known to be effective in transdermal delivery of drugs through intercellular lipids because of their unique small particle size. In this study, phase inversion temperature (PIT) nanoemulsion containing α-bisabolol was optimized using response surface methodology (RSM) for effective skin absorption of α-bisabolol. As a preliminary experiment, the 25-2 fractional factorial design method and the 23 full factorial design method were performed. Box-Behnken design was performed based on the results of the factorial design method. The content of surfactant (6.3~12.6%), co-surfactant (5.2~7.8%) and α-bisabolol (0.5~5.0%) were used as factors, and the dependent variable was the particle size of the nanoemulsion. PIT nanoemulsion optimization was performed according to the RSM results, and as a result, the optimal nanoemulsion formulation conditions were predicted to be 10.4% surfactant content, 6.3% co-surfactant content, and 5.0% α-bisabolol content. As a result of the skin absorption test, the final skin absorption rate of the PIT nanoemulsion was 35.11±1.01%, and the final skin absorption rate of the general emulsion as a control was 28.25±1.69%, confirming that the skin absorption rate of the PIT nanoemulsion was better.
Ha, Ki-Young;Park, Hojin;Park, Seung-Ha;Lee, Byung-Il;Ji, Yi-Hwa;Kim, Tae-Yeon;Yoon, Eul-Sik
Archives of Plastic Surgery
/
v.42
no.6
/
pp.677-685
/
2015
Background The survival rate of grafted fat is difficult to predict, and repeated procedures are frequently required. In this study, the effects of the freezing period of harvested adipose tissue and the addition of human adipose tissue-derived stem cells (ASCs) on the process of fat absorption were studied. Methods Adipose tissue was obtained from patients who underwent a lipoaspirated fat graft. The fat tissue was cryopreserved at $-20^{\circ}C$ in a domestic refrigerator. A total of 40 nude mice were used. The mice in the experimental group received three different subcutaneous injections in the back: an injection of fresh fat and ASCs, an injection of fat that had been frozen for one month and ASCs, and an injection of fat that had been frozen for two months and ASCs. The control mice received fat grafts without ASCs. The mice were sacrificed at four or eight weeks after the procedure, and the grafted fat tissues were harvested. The extracted fat was evaluated using photographic analysis, volume measurements, and histological examination. Results In the control group, the fat resorption rates four weeks after transplantation in the grafts of fresh fat, fat that had been frozen for one month, and fat that had been frozen for two months were 21.14%, 22.46%, and 42.56%, respectively. In the experimental group, the corresponding resorption rates were 6.68%, 13.0%, and 33.9%, respectively. Conclusions ASCs can increase the fat graft survival rate. The use of ASCs in fat grafting can reduce the need for repeated fat grafts and provide good long term results.
Journal of the Korean Applied Science and Technology
/
v.27
no.4
/
pp.407-414
/
2010
New biological treatments were being developed at a record place, but their potential could be compromised by a significant obstacle: the delivery of these drugs into a body. Pharmaceutical delivery is now nearly as important as product. New systems are being developed, and Drug Delivery Markets Series cover these new systems. Transdermal Delivery System(TDS) is often used as a method of drug dosage into the epidermic skin. An approach used to delivery drugs through the skin for therapeutic use as an alternative to oral, intravascular, subcutaneous and transmucosal routes. Various transdermal drug delivery technologies are described including the use of suitable formulations, carriers and penetration enhancers. The most commonly used transdermal system is the skin patch using various types of technologies. Compared with other methods of dosage, it is possible to use for a long term. It is also possible to stop the drug dosage are stopped if the drug dosage lead to side effect. Polysaccharides, such as karaya gum and glucomannan, were selected as base materials of TDS. Also, these polymers were characterized in terms of enhancers, drug contents. Among these polysaccharide, the permeation rate of karaya gum matrix was fastest in fibric acid(ciprofibrate) such as lipophilic drug in vitro. We used glycerin, PEG400 and PEG800 as enhancers. Since dermis has more water content(hydration) than the stratum corneum, skin permeation rate at steady state was highly influenced when PEG400 was more effective for lipophilic drug. Proper selection of the polymeric materials which resemble and enhance properties of the delivering drug was found to be important in controlling the skin permeation rate. Especially, this result suggests a possible use of polysaccharide gel ointment matrix as a transdermal delivery system of anti-hyperlipoproteinemic agent.
Administration route dependency on the distribution of PEGylated recombinant human turor necrosis factor binding protein (rhTNFbp-PEG20K dimer) was observed following a subcutaneous (sc) and an intravenous (iv) administrationin rats. ehTNFbp-PEG20K dimer is composed of two rhTNGbp molecules (molecular weight 18, 278 daltons each) joined by polyethylene glycol 2000(PEG30K). The steady state distribution volume of rhTNFbp-PEG20K was 55 m/kg and 359 ml/kg following the i.v. and s.c. administrations, respectively. These results suggest that the distribution of ehTNFbp-PEG20K is limited within the cpillary space after i.v. administration, while rhTNFbp-PEG20K can distribute into a space (35.9% of body weight) which is between extracellylar space and total body water. A lymphatic absorption may paly a role in the distribution of rhTNFbp-PEF20K dimer following the sc administration. The present study suggests that the administration route of a lartge protein molecule should be determined depedning upon target sites.
We established a new method to analyze abamectin using HPTLC (high performance thin layer chromatography) in order to obtain its pharmacokinetic profiles in pigs. Recovery of abamectin in pig serum after fluorescence derivatization was $80.01{\pm}3.82%$ at 0.1ppm and $83.67{\pm}3.63%$ at 10ppm, respectively. Detection reproducibility in terms of coefficient variation (c.v.) was 3.09% and 2.74% (intra-day), and 3.71% and 51.7%(inter-day), for 0.1 and 10ppm, respectively. Pharmacokinetics of abamectin was studied in five Yorkshire-Landrace mixed bred male pigs ($35.0{\pm}2.7kg$) administered intramuscularly 0.3mg/kg b.w. Pharmacokinetic profiles of abamectin in pigs were described by the 1-compartment open model with first-order absorption and first-order elimination. AUC (area under the curve) was $262.65{\pm}16.44ng{\cdot}day/ml$ and the biological elimination half-life ($t_{1/2},\;k_e$) was $5.28{\pm}0.84$ days, indicating somewhat high bioavailability and long half-life by the intramuscular route. We suggest intramucular injection of abamectin could be also used in place of the recommended route of its subcutaneous administration so far.
Two separate trials were designed to determine effects of dietary level of whole flaxseed (WFS) on fatty acid composition of serum, and subcutaneous, perirenal, intermuscular, and intramuscular adipose tissues of Korean Hanwoo cattle. Twentyone bulls (trial 1) and 15 cows (trial 2) were assigned to diets containing 0, 10 or 15% WFS. Relative treatment effects were similar between bulls and cows. The proportion of C18:3 in serum and to a lesser extent in adipose tissues were increased by dietary inclusion of WFS, reflecting supplemented lipid composition of WFS that escaped ruminal biohydrogenation. Animals fed WFS had a lower proportion of saturated fatty acids in serum and adipose tissues than animals fed diets without WFS, while the opposite trend was observed in unsaturated fatty acids with little differences between two WFS groups. WFS-fed animals had higher proportions of C18:1, 18:2, 18:3, 20:3, and 22:3 and lower proportions of C12:0, 14:0, 16:0 and 18:0 in intramuscular fat than animals fed diets without WFS. Furthermore, feeding WFS increased proportions of both $\omega$-3 and $\omega$-6 fatty acids but decreased the ratio of $\omega$-6/$\omega$-3 substantially. In conclusion, feeding WFS can be an effective method of increasing absorption of unsaturated fatty acids, and subsequent deposition in adipose tissues.
Purpose: With the recent recognition of the importance of soft-tissue fillers, fat grafting has been assumed an increasingly important role as both an adjunctive and a primary procedure in aesthetic and reconstructive surgery. The main problem in achieving long-term soft-tissue augmentation is partial absorption of the injected fat and hence the need for overcorrection and re-injection. The purpose of this study is to improve the viability of the injected fat by the use of Lipo-PGE1. Methods: Human adipose tissue, obtained by suctionassisted lipectomy, was re -injected into the subcutaneous layer in the scalp of ICR mice. Lipo-PGE1 ($0.5{\mu}g$/kg) was injected intravenously in experimental group for 7 days from the operation day and saline was injected in control group. There were 5 animals in each group. The animals were euthanized 4 weeks after the procedure. Graft weight and volume were measured and histologic evaluation was performed. Result: Histologic analysis demonstrated significantly less cyst formation and less inflammatory reaction in the group treated with Lipo-PGE1. No significant difference was found between the groups regarding graft volume or the other histologic parameters investigated. Significant differences were demonstrated in microvascular density count. Conclusion: Less cyst formation, less inflammation, more angiogenesis indicating improved quality of the injected fat can be obtained by the addition of Lipo-PGE1. Further studies of various dosages of Lipo-PGE1 and their long-term effect are required before these encouraging results could be applied clinically.
The present study was carried out to examine the effect of insulin formula on blood glucose change in normal Sprague-Dawley male rats. Also, this study was performed to investigate the feasibility of oral insulin formula development. To administrate the insulin formula into intestine, the surgical technique, celiotomy, was performed in rats. Insulin formula was administrated at a dose of 24.5 IU/kg via duodenum, ileum, and colon of the rats, and the blood glucose level was measured. For the comparison, the vehicle without insulin was administrated into ileum via celiotomy. Also, this insulin formula was administrated into rats orally using sonde and the same parameter was treasured. The bloods of all groups were collected from tail veins using syringes at given time interval. Orally administrated group did not show the change of blood glucose level and control group slightly show the change of blood glucose level at 1 hour after celiotomy. All intestinally administrated groups showed the change of blood glucose level. Among the tested groups, ileac administration group and colonic administration group showed the significant change of blood glucose level. Particularly, ileac administration group showed the lowest blood glucose level. To calculate the bioavailability of intestinal and oral administration, insulin solution was injected subcutaneosly, common insulin injection route, into another normal rats. The bioavailability of ileac group was 8.3% when compared with subcutaneous injection, duodenal group was 1.8%, colonic group was 4.2%, and oral group was 0.2%, respectively.
Purpose: Acellular human dermis is very useful implant for use in plastic and reconstructive surgery. However, the volume of acellular human dermis graft is known to decrease for a long time. Basic fibroblast growth factor (bFGF) is a polypeptide that enhances the collagen synthesis and angiogenesis. In the current study we examined whether bFGF could improve the survival of acellular human dermis ($SureDerm^{(R)}$) by increasing angiogenesis of the graft. Methods: Forty rats were divided into two groups (control and bFGF). A 2-mm thick piece of $SureDerm^{(R)}$ was cut into smaller pieces that were $15{\times}5$ mm in size. Two subcutaneous pockets were made on the back of each rat. Grafts sprayed with bFGF were implanted in the bFGF group and injected with bFGF after transplantation every 3 days for 2 weeks. In the control group, the grafts were treated with phosphate-buffered saline (PBS) instead of bFGF. Four days, and 1, 4, and 12 weeks after the implantation, the grafts were harvested and gross and histologic examinations were performed. Inflammation grade, graft thickness, neocollagen density, and neocapillary count were measured. Results: The bFGF group displayed more rapid accumulation of inflammatory cells with a higher density of neocapillaries, and increased active collagen synthesis. After 12 weeks, the thickness of the grafts in the control and bFGF groups was $75.15{\pm}4.80%$ and $81.79{\pm}5.72%$, respectively, in comparison to the thickness before transplantation. There was a statistically significant difference between both groups ($p$ <0.05). Conclusion: bFGF was effective in reducing the absorption of acellular human dermal grafts by increasing angiogenesis and accelerating engraftment. In conclusion, bFGF may be a good tool for use in acellular human dermal graft transplantation for reconstructive surgery involving soft-tissue defects.
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