• Journal of Pharmaceutical Investigation
• /
• 제36권3호
• /
• pp.185-192
• /
• 2006

The purpose of this study was to determine the effects of iontophoresis on transdermal delivery of procaine hydrochloride in healthy volunteers, as well as to the synergic effect of high voltage current or ultrasound on the efficacy of transdermal delivery of iontophoresis. Forty healthy volunteers were randomly assigned to four groups topical application group (TA), iontophoresis group (IT), pre-treatment of high voltage current stimulation with iontophoresis (HVS + IT), and pre-treatment of ultrasound application with iontophoresis (US + IT). All subjects received procaine iontophoresis on the forearm using direct current with 4 mA f3r 15 minutes. All subject was measured the duration of local anesthesia, pressure pain threshold, pain perception threshold using rectangular wave at 0.2 ms, 1 ms, 50 ms of rectangular current stimulation after procaine iontophoresis. For comparisons of the sensory characteristics and efficacy of iontophoresis between the groups, an one-way ANOVA and Kruskal-Wallis were used. The significant difference the duration of local anesthesia were found between the groups (p<0.001). The local anesthetic duration of IT, HVS+IT were significantly longer than TA. Meanwhile, the local anesthetic duration of US+IT was significantly longer than HVS+IT, IT and TA group (p<0.05). Also, the pressure pain threshold, pain perception threshold at 0.2 ms, 1 ms, 50 ms were significant difference between the groups (p<0.001). All sensory characteristics including pressure pain threshold, pain perception threshold of IT, HVS+IT was significantly increased than TA, whereas, US+1T was significantly increased HVS+1T, IT and TA (p<0.05). This study showed that the procaine iontophoresis have increase the duration of local anesthesia concomitantly pressure pain threshold and pain perception threshold of sensory nerve fibers such as $A-{\beta}$, $A-{\delta}$ and C fiber. This findings suggest that the iontophoresis enhanced the transdermal delivery of drug ions in vivo. The combination of ultrasound application and iontophoresis synergized the transdermal delivery of drug ions. It is suggests that an electric field, mechanical and heating property of ultrasound may contribute to synergic effect due to temporary changes of structure in the stratum corneum.

• Journal of Pharmaceutical Investigation
• /
• 제28권2호
• /
• pp.87-92
• /
• 1998

Kojic acid (KA) is an antimelanogenic agent which has been widely used in cosmetics to whiten the skin color. However, it has the drawbacks of the skin irritancy and the instability against the pH, temperature, and light. In order to overcome these problems, various topical gels and multiple emulsion creams which can control the release of active ingredient, KA, were formulated employing cream bases of mineral oil with caprylic capric triglyceride and hydrophilic polymers such as chitosan, carbopol. and pluronics. Using Franz diffusion cells mounted with a synthetic cellulose membrane (MWCO 12,000), drug release characteristics of the formulations were evaluated by the HPLC assay of KA concentration in the receptor compartment of pH 7.4 phosphate buffered saline solution. Drug release from chitosan-based gels (ChitoGel) obeyed to the first order kinetics with a rapid release especially in the initial period. However, pluronic-based gels (PluGel) and carbopol-based gels (CarboGel) revealed controlled release of drug to some extent, followed by the square root-time kinetics. Moreover, the release of KA was further controlled with the W/O/W multiple emulsion creams (MultiCream), showing the apparent zero order release kinetics by virtue of dynamic ratecontrolling membrane of the oil layer. The flux $(J,\;{\mu}g/cm^2/hr)$ of ChitoGel. CarboGel. PluGel. and MultiCream in the initial period of 6hr were 73.30, 28.67. 24.04 and 7.72, respectively. On the other hand, the skin irritancy score of ChitoGel and MultiCream were observed as 2.5 and 2.3 respectively, in the rabbit skin irritation test. Although there were insignificant differences at p<0.05 between those formulations, it was possible to conclude that the W/O/W multiple emulsion creams containing KA might be a good candidate for an antimelanogenic drug delivery system due to the controlled release of acidic drug molecules.

• Journal of Photoscience
• /
• 제9권2호
• /
• pp.225-228
• /
• 2002

Bcl-2 is a member of large bcl-2 family and protects cells from apoptosis. Using bcl-2-expressing adenovirus vector (Ad-bc1-2), we investigated the effect of bc1-2 on UVB-induced apoptosis. Adenovirus vector efficiently introduced bc1-2 gene in cultured normal mouse keratinocytes (NMK cells); almost all NMK cells (lx10$^{6}$ ) were transfected at Ixl0$^{8}$ PFU/ml. Bcl-2-transfected NMK cells were significantly resistant to UVB-induced apoptosis with the suppressive effect dependent on bcl-2-expression level. Following UVB irradiation caspase 8, 3, 9 activities were stimulated in NMK cells, while in bc1-2-transfected cells, only caspase 8, but not caspase 3 or 9 activities were stimulated. In order to investigate the effect of bc1-2 in vivo, topical application of Ad-bc1-2 on tape-stripped mouse skin was performed. Following the application, Bc1-2 was efficiently overexpressed in almost all viable keratinocytes. The expression was transient with the maximal expression of Bc1-2 at 1st day following the application of lxl0$^{9}$ PFU in 200ml. The introduced Bc1-2 remained at least for 6 days. UVB irradiation (1250 J/m$^2$) induced apoptosis within 12 h and the maximal effect was observed at 24 h in control mouse skin. Bc1-2-transfected mice skin were resistant to UVB-induced apoptosis. Topical application of empty adenovirus vector alone had no effect on Bc1-2 expression or UVB-induced apoptosis. These results indicate that adenovirus vector is an efficient gene delivery system into keratinocytes and that Bcl-2 is a potent inhibitor of UVB-induced apoptosis both in vitro and in vivo.

• Journal of Oral Medicine and Pain
• /
• 제35권4호
• /
• pp.229-235
• /
• 2010

일반적으로 약물은 경구투여를 우선으로 한다. 그것은 환자에게 투여하기가 가장 쉬운 방법이기 때문이다. 하지만 경구투여를 하는 경우 인체에서 약물이 분해 및 흡수되면서 거치는 과정 중에 상당수가 없어지고 약효를 발휘하는 부분은 그다지 많지 않다. 그러다 보니 적절한 혈중 농도를 유지하기 위하여 실제 필요한 약물의 양보다 많은 양을 투여하게 되므로, 부수적으로 따라다니는 약의 부작용 또한 증가하게 된다. 피부질환의 경우에는 약물의 흡수를 돕도록 하는 많은 첨가물과 함께 개발된 외용제가 있다. 대부분 크림형태로 시판되고 있으며 약효를 내는 용량을 피부에 도포하였을 때 전신으로 흡수되는 양은 많지 않아 부작용이 적은 것이 장점이다. 구강점막은 자연적인 barrier가 많은 피부와 달리 혈관까지 도달하는 길이가 짧고, 도포가 어려운 장점막과 달리 접근성이 용이하다. 따라서 도포용 약물의 개발이 많이 시도되고 있으나 타액에 의해 많은 부분이 세척되어 없어지거나 타액속의 물질들로 인하여 변질이 일어나고 있어 피부와 같은 크림형 제제의 개발이 어려운 실정이다. 따라서 현재 판매되고 있는 구강내 외용제는 그 수가 매우 제한되어 있다. 도포용 약물을 개발하여 오래 구강점막에 부착하게 하는 것이 용이하지 않으므로 임상가들이 약물을 용액 형태로 사용하여 환자에게 도포하고 있다. 이러한 용액을 머금고 있다가 뱉어내게 하는 가글형태의 약물도포 또한 그 약효가 인정되고 있다. 따라서 현재 임상에서 도포형태로 사용하고 있는 약물의 종류와 효과, 그리고 일반적인 경구투여 약물을 적절한 용해제를 선택하여 용액으로 사용하였을 때 임상적으로 기대할 만한 약효를 발휘할 수 있을지에 대하여 연구해 본다.

• Biomolecules & Therapeutics
• /
• 제16권3호
• /
• pp.226-230
• /
• 2008

Monoolein-based cubic liquid crystalline systems were formulated for the local delivery of oregonin and hirsutanonol for the treatment of atopic dermatitis. The liquid crystalline phase and its nanodispersion containing drugs were prepared. The skin permeation and deposition properties of the drugs were examined in normal and delipidized rat skin. The proportion of oregonin (%) deposited in normal skin after topical administration of the drugs in the form of aqueous solution, cubic phase or cubic nanodispersions were $1.53\;{\pm}\;0.46$, $3.62\;{\pm}\;0.17$ and $5.13\;{\pm}\;0.73$, and those of hirsutanonol were $2.46\;{\pm}\;0.02$, $5.44\;{\pm}\;0.27$ and $17.28\;{\pm}\;2.19$, respectively. The greater lipophilicity and thus greater skin affinity of hirsutanonol than oregonin contributed the greater amount of skin deposition. The monoolein-based liquid crystalline phases significantly increased the amount of both drugs permeated and deposited. Approximately 3.2, 2.1 and 3.0 times greater amount of oregonin, and 3.4, 2.1 and 2.2 times greater amount of hirsutanonol were deposited in delipidized skin after administration of each drug in the form of aqueous solution, cubic phase and cubic nanodispersions system, respectively, because of lowered barrier function of the delipidized skin. In this study, the effects of drug property, vehicles type and skin condition on skin deposition and permeation properties of drug were examined and concluded that monoolein-based liquid crystalline systems would be a promising formulation for the local delivery of drugs.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1995년도 춘계학술대회
• /
• pp.79-79
• /
• 1995

Although synthetic antisense oligodeoxynucleotides (ODNs) have been used to dissect gene function in vitro, technical difficulties of targeted delivery prevented the use of this approach for investigating the effect of gene products in vivo. Here we report the use of local delivery of antisense transforming growth factor-${\beta}$l (TGF-${\beta}$1) oligonucleotides to decrease the fibrosis in the skin wound. Adult wounds heal with scar-tissue formation, whereas fetal wounds heal without scarring and with a lesser inflammatory and cytokine response. We reasoned that strategy emptying antisense TGF-${\beta}$1 ODNs complementary to TGF-${\beta}$1 mRNA might decrease the scarring in dermal wound of mouse. To evaluate this concept, we tested the effects of antisense ODNs targeted to TGF-${\beta}$1 mRNA by topical application of the chemical on the skin wound. Phosphorothioate antisense ODNs was employed to retard their degradation. When antisense TGF-${\beta}$1 ODNs were applied into the wound site, there was a maked reduction of scar compared with control wound site, These effects of antisense TGF-${\beta}$1 ODNs on the scar formation were associated with decreased expression of TGF-${\beta}$1 gene. However sense TGF-${\beta}$l ODNs had no effect on expression of TGF-${\beta}$1 gene. Also, control wounds healed with excessive fibrosis, whereas the antisense treated wounds healed with less fibrosis. In conclusion, our results indicate that antisense TGF-${\beta}$1 ODNs could be used for amelioating scar formation during wound healing.

• Archives of Pharmacal Research
• /
• 제29권12호
• /
• pp.1187-1192
• /
• 2006

The aims of this study were to encapsulate arbutin (AR) in liposome to enhance the skin-whitening activity, and to investigate the effect of liposome formulation on the entrapment efficiency (EE%), skin permeation rate and skin deposition. The liposomes were prepared by a film dispersion method with several different formulations and were separated from the solution by using the gel-filtration method. The physical (size distribution, morphology) and chemical (drug entrapment efficiency, hairless mouse skin permeation and deposition) properties of liposomes were characterized. The entrapment efficiency in all liposome formulations varied between 4.35% and 17.63%, and was dependent on the lipid content. The particle sizes of liposomes were in the range of $179.9{\sim}212.8\;nm$ in all liposome formulations. Although the permeation rate of AR in the liposome formulations decreased compared with AR solution, the deposition amount of AR in the epidermis/dermis layers increased in AR liposomal formulation. These results suggest that liposomal formulation could enhance the skin deposition of hydrophilic skin-whitening agents, thereby enhancing their activities.

• Journal of Chest Surgery
• /
• 제24권7호
• /
• pp.669-673
• /
• 1991

Fructose-l, 6-diphosphate as an additive to cold crystalloid cardioplegia [St. Thomas sol.] was studied prospectively in 60 patients undergoing open heart surgery from January 1, 1991, to June 30, 1991. Thirty patients received cardioplegia with FDP[group I ] and 30 patients received cardioplegia without FDP [group II ]. There were no differences between two groups pre-operatively with regard to age, heart disease, cross-clamp time, cardiac enzymes, or hemodynamic measurements [p>0.05]. Cardiopulmonary bypass was established using ascending aorta and vena cava cannulation employing moderate systemic hypothermia [30oC nasopharyngeal temperature] and hemodilution All patients received cardioplegia through the aortic root at aortic root pressure of 80mm Hg. The composition of the cardioplegic solution and its delivery were identical in both groups except for the addition of FDP[1.5 mg/mL] in group I. The cardioplegic infusate consisted of St. Thomas Hospital solution. The initial dose was infused through the aortic root. Topical myocardial cooling with saline slush was employed in all patients. Recorded operative data were cardiopulmonary bypass and cross-clamp times, amount of cardioplegic infusate. Blood samples for assessment of lactate dehydrogenase [LDH], creatine kinase [CK] and transaminases [GOT, GPT] were obtained before and at 1,2,3,7th postoperative period. Better myocardial protection effect was noted in group I than group II with respect to the % change of cardiac enzymes, although the differences were not significant. We conclude that FDP is a safe additive to crystalloid cardioplegia and may be beneficial in open heart surgery patients.

• Journal of Pharmaceutical Investigation
• /
• 제36권5호
• /
• pp.305-308
• /
• 2006

Poloxamer-based hydrogel formulation for the topical delivery of ascorbic acid(AsA) was prepared and the effect of limonene on AsA skin permeation and localization was evaluated. In vitro rat skin permeation study, the AsA skin permeation of limonene-containing hydrogel was about 3 to 5 fold higher than control hydrogel. However the amount of permeated AsA was independent to the concentration of limonene. On the other hand the localized amount of AsA after 2 h increased proportion to the content of limonene. The increase in the ratio of localized AsA($Q_L$) to permeated AsA($Q_P$) was attributed to the limonene's ability of making polar pathway within stratum corneum by interacting on lipid domain of the skin and the AsA's hydration effect on the stratum corneum and effect on the protein domain of the skin.

• Journal of Pharmaceutical Investigation
• /
• 제19권3호
• /
• pp.145-154
• /
• 1989

Methyl methacrylate-butyl methacrylate copolymer (MMBM)-povidone (PVP) films were investigated as a potential topical drug delivery system for the controlled release of econazole nitrate as a model drug. The effect of changes in film composition, drug concentration, film thickness, pH and temperature of release medium on the in vitro release of econazole nitrate were studied. The release rate constant was found to be increased with increasing povidone content in dry films. Drug release followed zero-order kinetics in the initial stage and then release rate increased gradually with time, espicially in the films having larger proportions of PVP. The release rate was found to be dependent on drug content, film thickness, the pH and temperature of release medium. Antimicrobial test showed that microbial growth was inhibited markedly with increasing proportions of PVP in films. Also drug content and film thickness affected the antimicrobial activity.