• Title/Summary/Keyword: Drug-delivery

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In Vivo Neuroprotective Effect of Histidine-Tryptophan-Ketoglutarate Solution in an Ischemia/Reperfusion Spinal Cord Injury Animal Model

  • Kang, Shin Kwang;Kang, Min-Woong;Rhee, Youn Ju;Kim, Cuk-Seong;Jeon, Byeong Hwa;Han, Sung Joon;Cho, Hyun Jin;Na, Myung Hoon;Yu, Jae-Hyeon
    • Journal of Chest Surgery
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    • v.49 no.4
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    • pp.232-241
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    • 2016
  • Background: Paraplegia is a devastating complication following operations on the thoracoabdominal aorta. We investigated whether histidine-tryptophan-ketoglutarate (HTK) solution could reduce the extent of ischemia/reperfusion (IR) spinal cord injuries in a rat model using a direct delivery method. Methods: Twenty-four Sprague-Dawley male rats were randomly divided into four groups. The sham group (n=6) underwent a sham operation, the IR group (n=6) underwent only an aortic occlusion, the saline infusion group (saline group, n=6) underwent an aortic occlusion and direct infusion of cold saline into the occluded aortic segment, and the HTK infusion group (HTK group, n=6) underwent an aortic occlusion and direct infusion of cold HTK solution into the occluded aortic segment. An IR spinal cord injury was induced by transabdominal clamping of the aorta distally to the left renal artery and proximally to the aortic bifurcation for 60 minutes. A neurological evaluation of locomotor function was performed using the modified Tarlov score after 48 hours of reperfusion. The spinal cord was harvested for histopathological and immunohistochemical examinations. Results: The spinal cord IR model using direct drug delivery in rats was highly reproducible. The Tarlov score was 4.0 in the sham group, $1.17{\pm}0.75$ in the IR group, $1.33{\pm}1.03$ in the saline group, and $2.67{\pm}0.81$ in the HTK group (p=0.04). The histopathological analysis of the HTK group showed reduced neuronal cell death. Conclusion: Direct infusion of cold HTK solution into the occluded aortic segment may reduce the extent of spinal cord injuries in an IR model in rats.

Physical Characteristic and In vitro Transdermal Delivery of PCL-b-PEG Micelles Containing Quercetin and Rutin (Quercetin과 Rutin을 함유하는 PCL-b-PEG 고분자 미셀의 특성 및 피부 흡수에 관한 In vitro 연구)

  • Lim, Gyu-Nam;Kim, Sun-Young;Kim, Min-Ji;Park, Soo-Nam
    • Polymer(Korea)
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    • v.36 no.4
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    • pp.420-426
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    • 2012
  • In this study, we prepared polymer micelles containing quercetin and rutin, known as antioxidants, using poly(${\varepsilon}$-caprolactone)-b-poly(ethylene glycol), and evaluated in vitro skin permeation of the active materials. Quercetin and rutin loaded micelles were characterized by DSC (differential scanning calorimetry), HPLC (high performance liquid chromatography) and DLS (dynamic light scattering) measurements. The particle size of the polymer micelles increased in a concentration dependent manner (0.5~2.0% PCL-b-PEG). The Zeta potential of quercetin and rutin loaded micelles remained constant. To evaluate the skin penetration of PCL-b-PEG micelles, Franz diffusion cell experiment was performed. The aqueous solutions of quercetin and rutin were used as the control groups. Quercetin and rutin loaded PCL-b-PEG micelles showed more efficient skin permeation than the control groups. Safety assessment (patch test) of quercetin and rutin loaded PCL-b-PEG micelles on skin was performed to test application possibility of the polymer micelles to cosmetics. Any adverse symptoms were not observed.

Study on Optimization and Skin Permeation of PIT Nanoemulsion Containing α-Bisabolol (α-Bisabolol을 함유한 PIT Nanoemulsion의 최적화 및 피부흡수연구)

  • Kim, HuiJu;Yoon, Kyung-Sup
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.6
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    • pp.1738-1751
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    • 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.

Effect of PEG chain additive on 6,8-dichloro-2-phenylimidazo[1,2-a] pyridineacetamide (CB185) as a TSPO-binding ligand

  • Lee, Won Chang;Lee, Sang Hee;Denora, Nunzio;Laquintana, Valentino;Lee, Byung Chul;Kim, Sang Eun
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.5 no.2
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    • pp.89-100
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    • 2019
  • In our previous studies, we developed a 18F-labeled TSPO-binding ligand, named [18F]CB251, which has been proved to be a promising TSPO-binding PET radiotracer for the detection and monitoring of TSPO expression in pathological diseases. (Ki = 0.27 nM for TSPO, 1.96% ID/g of tumor uptake at 1h post-injection) Based on these results, we utilized 6,8-dichloro-2-phenylimidazo[1,2-a]pyridineacetamide analogs, CB185 (1) as a targeting moiety for the selective delivery of probes and anticancer molecules to TSPO-overexpressed tissues. In this study, we designed CB185 derivatives contains different PEG chains (n = 1, 3 and 5) and fluorescence dye (Cy5) to identify the necessary space between a TSPO-binding ligand and an anticancer agent. Three CB185 derivatives (11a-c) which contains Cy5 and PEG chain, were synthesized and the effect of PEG additive on their TSPO-binding affinities were evaluated using in vitro assays. The binding affinity for compounds 11a-c was lower than that of PK11195 (Ki = 3.2 nM), but still characterized by nanomolar binding affinity for TSPO (Ki = 46.5 nM for 11a, 51.0 nM for 11b, and 388.5 nM for 11c). These results showed that the conjugates are characterized by a moderate binding affinity toward TSPO except for compound 11c, which PEG chain consist of five PEG monomers. Our finding might add useful information to decide the appropriate PET chain length for developing new TSPO-targeting drug carriers.

Upregulation of Mir-34a in AGS Gastric Cancer Cells by a PLGA-PEG-PLGA Chrysin Nano Formulation

  • Mohammadian, Farideh;Abhari, Alireza;Dariushnejad, Hassan;Zarghami, Faraz;Nikanfar, Alireza;Pilehvar-Soltanahmadi, Yones;Zarghami, Nosratollah
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8259-8263
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    • 2016
  • Background: Nano-therapy has the potential to revolutionize cancer therapy. Chrysin, a natural flavonoid, was recently recognized as having important biological roles in chemical defenses and nitrogen fixation, with anti-inflammatory and anti-oxidant effects but the poor water solubility of flavonoids limitstheir bioavailability and biomedical applications. Objective: Chrysin loaded PLGA-PEG-PLGA was assessed for improvement of solubility, drug tolerance and adverse effects and accumulation in a gastric cancer cell line (AGS). Materials and Methods: Chrysin loaded PLGA-PEG copolymers were prepared using the double emulsion method (W/O/W). The morphology and size distributions of the prepared PLGA-PEG nanospheres were investigated by 1H NMR, FT-IR and SEM. The in vitro cytotoxicity of pure and nano-chrysin was tested by MTT assay and miR-34a was measured by real-time PCR. Results: 1H NMR, FT-IR and SEM confirmed the PLGA-PEG structure and chrysin loaded on nanoparticles. The MTT results for different concentrations of chrysin at different times for the treatment of AGS cell line showed IC50 values of 68.2, 56.2 and $42.3{\mu}M$ and 58.2, 44.2, $36.8{\mu}M$ after 24, 48, and 72 hours of treatment, respectively for chrysin itslef and chrysin-loaded nanoparticles. The results of real time PCR showed that expression of miR-34a was upregulated to a greater extent via nano chrysin rather than free chrysin. Conclusions: Our study demonstrates chrysin loaded PLGA-PEG promises a natural and efficient system for anticancer drug delivery to fight gastric cancer.

Release Behavior of 5-FU from 5-FU/PLGA Wafer using Recrystallized PLGA and Monomer (재결정 PLGA와 단량체를 이용한 5-FU/PLGA 웨이퍼의 방출거동)

  • Park, Jung Soo;Choi, Myoung Kyu;Kim, Yun Tae;Lee, Jun Hee;Mo, Jong Hyun;Khang, Gilson;Rhee, John Moon;Shin, Hyung Shik;Lee, Hai Bang
    • Korean Chemical Engineering Research
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    • v.46 no.2
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    • pp.205-210
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    • 2008
  • Poly(D,L-lactide-co-glycolide) (PLGA) has been widely used as carriers in controlled release delivery systems due to its biodegradability and relatively good biocompatibility. However, Release pattern of carriers fabricated using PLGA have disadvantage an initial burst within a few days, lag time several days and then sudden release changes. To solve these problems of PLGA, we fabricated PLGA wafer including monomer. Also, drug release behavior restraint sudden burst effect using recrystallization of PLGA. Recrystallized PLGA was characterized the morphological difference by SEM and in vitro release behavior measured by HPLC. The PLGA molecular weight analyzed to recognize monomer influence during degradation process of polymer using GPC. In this study, drug release duration cut short up to three days and was eliminated the lag time based on the bulk erosion.

Evaluation of Physical Properties and Biocompatibility of HA-Dex Fusion Hydrogel Patch for Atopic Healing Ability (HA-Dex 융복합 하이드로겔 패치의 아토피 치유 능력에 대한 물리적 특성 및 생체 적합성 평가)

  • Hong, Gyeong Sik;Choi, Jeong Yeon;Choi, Jin Hyun
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.46 no.3
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    • pp.219-229
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    • 2020
  • Recently, since atopic dermatitis is sensitive to skin irritation, it has been suggested that the development of a patch that can effectively exhibit adhesion and absorption to a specific local area while minimizing skin irritation, and capable of appropriate drug release should be given priority. In this study, we tried to develop a hydrogel patch that minimizes skin irritation, adheres effectively to a specific area, and promotes absorption. The atopic patch was formulated into a super-absorbent hydrogel sheet using a freeze drying method. Cell viability assay was carried out using keratinocytes (HaCaT cell) and fibroblasts (L929 cells). In order to investigate the physical properties, FT-IR, FE-SEM, porosity analysis and swelling behavior were investigated. As a result, the newly prepared HA-Dex hydrogel patch was verified by biocompatibility and physical evaluation. In addition, the manufactured hydrogel patch has sufficient moisture absorption capacity and can relieve itching of atopic skin, and is expected to be applied to various drug delivery products for the treatment of atopic dermatitis in the future.

The Release of Albumin from PLGA and PCL Wafers Containing Natural and Synthetic Additives for Protein Delivery (단백질 전달체로서 천연 및 합성재료의 첨가에 따른 PLGA와 PCL웨이퍼로부터 알부민의 방출거동)

  • Hyun Hoon;Lee Jae Ho;Seo Kwang Su;Kim Moon Suk;Rhee Jhon M.;Lee Hai Bang;Khang Gilson
    • Polymer(Korea)
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    • v.29 no.5
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    • pp.468-474
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    • 2005
  • PLGA and PCL copolymers initiated by carbitol as drug carriers were synthesized by ring-opening polymerization of L-lactide (LA), glycolide (GA), and $\varepsilon-caprolactone(\varepsilon-CL)$. Implantable wafers were simply fabricated by direct compression method after physical mixing of copolymers and bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) as a model protein drug. The release amounts of BSA-FITC from wafers were determined by fluorescence intensity using the fluorescence spectrophotometer. Also, the release behavior of BSA-FITC on wafers was controlled by adding the additives such as collagen, small intestinal submucosa (SIS), poly(vinyl pyrrolidone) (PVP), and poly(thylene glycol) (PEG). The wafer prepared by PLGA and PCL exhibited slow release within $10\%$ for 30 days. But, those prepared by a variety of additives exhibited the controlled BSA release patterns with a dependence on the additive contents. furthermore, the wafers containing natural materials such as collagen and SIS showed more zero-order release profile than that with synthetic materials such as PVP and PEG. It was confirmed that the release of BSA from implantable wafers could be easily controlled by adding natural additives.

Analysis of the Influence of Holding Pharmacist Specialization for Professionalism and Job Satisfaction (전문약사 자격 보유여부에 따른 전문성 및 직무만족도 영향 분석)

  • Jung, Sun Hoi;Choi, Kyung Hee;Kwon, Kyeng Hee;Rhew, Kiyon
    • Journal of Korean Society of Health-System Pharmacists
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    • v.35 no.4
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    • pp.441-452
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    • 2018
  • Background : The prevalence of the chronic metabolic disease is increasing due to the aging society. Therefore, Korean Society of Health-system Pharmacists (KSHP) has a specialty pharmacist system to improve the professionalism of pharmacists. The purpose of this study is to suggest the difference between specialty pharmacist and non-specialty pharmacist with regards to their knowledge, delivery of information on medication, service provision, and job satisfaction. Methods : An online survey research was conducted for hospital pharmacists. The reliability of the questionnaire items was presented using Cronbach's ${\alpha}$ test. The t-test or ANOVA analysis was used for evaluating differences in continuous variables. Results : A total of 171 pharmacists responded to the questionnaire, and 87.7% of the respondents were aged less than 30 years (76.6%) and four-year graduates (86.0%). Typically, 108 (63.2%) were candidates for the pharmacist's specialty certificate, and the remaining 63 (36.8%) were not enrolled. Considering the field of specialty with overlapping, the total number of certificated patients was 140 (26.3% of the total of 532 in 2016). The results of the reliability analysis of the specific questionnaire showed that the Cronbach's ${\alpha}$ value was over 0.78. There was no significant difference in customer directionality between the two groups. However, there was a significant difference (p<0.05) with respect to overall knowledge about the treatment process, drug efficacy, and side effects, information about medicines and adverse drug reactions, and in providing appropriate information to medical staff including patients and physicians. Conclusions : The pharmacist with specialization showed a positive result of self-evaluation of items such as knowledge about drugs, communication of information on medications, and service provision, compared to other pharmacists, and the result was in correlation with the numbers of specialization. There was no difference in job satisfaction related to working environment. Henceforth, it is hypothesized that there is a necessity for continuous improvement in the working environment to suit the purpose of the pharmacy specialist system.

Oncolytic Viruses - A New Era for Cancer Therapy (종양 용해성 바이러스-암 치료에서의 새 시대)

  • Ngabire, Daniel;Niyonizigiye, Irvine;Kang, Min-jae;Kim, Gun-Do
    • Journal of Life Science
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    • v.29 no.7
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    • pp.824-835
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    • 2019
  • In recent decades, oncolytic viruses (OVs) have extensively been investigated as a potential cancer drug. Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses. In order to overcome these hurdles, various strategies to enhance the efficacy of oncolytic viruses have been developed which include the insertion of transgenes or combination with immune-modulatory substances.