• Title/Summary/Keyword: systemic delivery

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Preparation of 5-Fluorouracil-Loaded Poly(L-lactide-co-glycolide) Wafer and Evaluation of In Vitro Release Behavior

  • Lee, Jin-Soo;Chae, Gang-Soo;An, Tae-Kun;Gilson Khang;Cho, Sun-Hang;Lee, Hai-Bang
    • Macromolecular Research
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    • 제11권3호
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    • pp.183-188
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    • 2003
  • The controlled delivery of anticancer agents using biodegradable polymeric implant has been developed to solve the problem of penetration of blood brain barrier and severe systemic toxicity. This study was performed to prepare 5-FU-loaded poly (L-lactide-co-glycolide) (PLGA) wafer fabricated microparticles prepared by two different method and to evaluate their release profile for the application of the treatment of brain tumor. 5-FU-loaded PLGA microparticles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (XRD), and differential scanning calorimetry (DSC). SEM observation of the 5-FU-loaded PLGA microparticles prepared by rotary solvent evaporation method showed that 5-FU was almost surrounded by PLGA and significant reduction of crystallinity of 5-FU was confirmed by XRD. In case of release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by mechanical mixing, the release profile of 5-FU followed near first order release kinetics. In contrast to the above result, release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by rotary solvent evaporation method followed near zero order release kinetics. These results indicate that preparation method of the 5-FU-loaded PLGA microparticles to fabricate into wafers was contributed to drug release profile.

Role of salvage radiotherapy for regional lymph node recurrence after radical surgery in advanced gastric cancer

  • Kim, Byoung Hyuck;Eom, Keun-Yong;Kim, Jae-Sung;Kim, Hyung-Ho;Park, Do Joong
    • Radiation Oncology Journal
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    • 제31권3호
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    • pp.147-154
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    • 2013
  • Purpose: To evaluate the role of salvage radiotherapy (RT) for the treatment of regional lymph node recurrence (RLNR) after radical surgery in advanced gastric cancer. Materials and Methods: We retrospectively analyzed medical records of 26 patients who underwent salvage treatment after diagnosis of RLNR between 2006 and 2011. Patients with peritoneal seeding or distant metastasis were excluded. Eighteen patients received RT with or without chemotherapy and the other 8 did chemotherapy only without RT. A three-dimensional conformal RT was performed with median dose of 56 Gy (range, 44 to 60 Gy). Sixteen patients had fluoropyrimidine-based chemotherapy, 5 did taxane-based chemotherapy, and irinotecan was applied in 4. Results: With a median follow-up of 20 months (range, 5 to 57 months), median overall survival (OS) and progression-free survival (PFS) after diagnosis of RLNR were 29 months and 12 months in the entire patients, respectively. Radiotherapy (p = 0.007) and disease-free interval (p = 0.033) were statistically significant factors for OS in multivariate analysis. Median OS was 36 months in patients who received RT and 16 months in those who did not. Furthermore, delivery of RT (p < 0.001), complete remission after salvage treatment (p = 0.040) and performance status (p = 0.023) were associated with a significantly better PFS. Gastrointestinal toxicities from RT were mild in most patients. Conclusion: Salvage RT combined with systemic chemotherapy may be an effective treatment managing RLNR from advanced gastric cancer.

바이러스 질병 예방을 위한 식물 경구 백신 연구 동향 (Recent Studies of Edible Plant Vaccine for Prophylactic Medicine against Virus-mediated Diseases)

  • 한범수;박종석;김형국;하선화;조강진;김용환;김종범
    • Journal of Plant Biotechnology
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    • 제31권2호
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    • pp.151-161
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    • 2004
  • Transgenic plants have been studied as delivery system for edible vaccine against various diseases. Edible plant vaccines have several potential advantages as follows: an inexpensive source of antigen, easy administration, reduced need for medical personnel, economical to mass produce and easy transport, heat-stable vaccine without refrigerator, generation of systemic and mucosal immunity and safe antigen without fetal animal-virus contaminants. The amount of recombinant antigens in transgenic plants ranged from 0.002 to 0.8% in total soluble protein, depending on promoters for the expression of interested genes and plants to be used for transformation. Throughout the last decade, edible plant vaccine made notable progresses that protect from challenges against virus or bacteria. However edible plant vaccines have still problems that could be solved. First, the strong promoter or inducible promoter or strategy of protein targeting could be solved to improve the low expression of antigens in transgenic plants. Second, the transformation technique of target plant should be developed to be able to eat uncooked. Third, marker-free vector could be constructed to be more safety. In this review we describe advances of edible plant vaccines, focusing on the yields depending on plants/promoters employed and the results of animal/clinical trials, and consider further research for the development of a new plant-derived vaccine.

Durogesic 부착포로 인한 fentanyl 중독 1례 (A Case of Fentanyl Toxicity with Misused Durogesic Transdermal Patch)

  • 윤성현;정현민;김지혜;한승백;김준식;백진휘
    • 대한임상독성학회지
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    • 제11권1호
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    • pp.49-52
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    • 2013
  • Fentanyl, a synthetic, highly selective opioid ${\mu}$-receptor agonist, is 50 to 100 times more potent than morphine. The low molecular weight, high potency, great transdermal permeation rate and lipid solubility of fentanyl make it very suitable for transdermal administration. Durogesic is a novel matrix transdermal system providing continuous systemic delivery of fentanyl. In recently, there are many reports that misused or overused fentanyl transdermal patches result in severe intoxication of fentanyl. We present a case of fentanyl toxicity with misused durogesic transdermal patch and discuss the safe and appropriate application of the patches. In conclusion, fentanyl patches should be used in opioid tolerant patients and prescribed at the lowest possible dose and titrated upward as needed. All patients and their caregivers should be educated safe application of fentanyl patches and advised to avoid exposing the patches application site to direct external heat sources, such as heating pads, or electric blankets, heat lamps, sauna, hot tubs, and others. In addition, concomittant medications that affect fentanyl's metabolism should be avoided.

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Tumoral Accumulation of Long-Circulating, Self-Assembled Nanoparticles and Its Visualization by Gamma Scintigraphy

  • Cho, Yong-Woo;Kim, Yoo-Shin;Kim, In-San;Park, Rang-Woon;Oh, Seung-Jun;Moon, Dae-Hyuk;Kim, Sang-Yoon;Kwon, Ick-Chan
    • Macromolecular Research
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    • 제16권1호
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    • pp.15-20
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    • 2008
  • The enhanced permeability and retention (EPR) effect is used extensively for the passive targeting of many macromolecular drugs for tumors. Indeed, the EPR concept has been a gold standard in polymeric anticancer drug delivery systems. This study investigated the tumoral distribution of self-assembled nanoparticles based on the EPR effect using fluorescein and radio-labeled nanoparticles. Self-assembled nanoparticles were prepared from amphiphilic chitosan derivatives, and their tissue distribution was examined in tumor-bearing mice. The size of the nanoparticles was controlled to be 330 run, which is a size suited for opening between the defective endothelial cells in tumors. The long-circulating polymer nanoparticles were allowed to gradually accumulate in the tumors for 11 days. The amount of nanoparticles accumulated in the tumors was remarkably augmented from 3.4%ID/g tissue at 1 day to 25.9%ID/g tissue at 11 days after i.v. administration. The self-assembled nanoparticles were sustained at a high level throughout the 14 day experimental period, indicating their long systemic retention in the blood circulation. The ${\gamma}$-images provided clear evidence of selective tumor localization of the $^{131}I$-labeled nanoparticles. Confocal microscopy revealed the fluorescein-labeled nanoparticles to be preferentially localized in the perivascular regions, suggesting their extravasation to the tumors through the hyperpermeable angiogenic tumor vasculature. This highly selective tumoral accumulation of nanoparticles was attributed to the leakiness of the blood vessels in the tumors and their long residence time in the blood circulation.

초산모 영아의 월령별 모유수유양상 및 모유수유건강행위실천에 관한 연구 (Breast-feeding & Breast-feeding Health Behavior among first-time mothers)

  • 박은옥;이건세;장인순;전경자
    • 여성건강간호학회지
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    • 제7권3호
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    • pp.382-392
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    • 2001
  • The purpose of this study is to investigate breast-feeding and breast-feeding health behavior among korean first-time mothers and to provide basic data for promoting breast- feeding. Data were collected by interview or self report from 444 first-time mothers who visited health clinic center in the area of metropolitan, medium or small city, countryside. and whose infants were under 12 months old from January 2001 to February 2001. The results show that breast-feeding was 31.5% in a week after childbirth, 25.8% in 4 weeks after childbirth, 22.7% in 2 months, 17.8% in 3 months, 14.3% in 6 months, 2.5% in 12 months after childbirth. Breast-feeding rate was very low in Korea and the duration of breast-feeding was very short. Breast-feeding health behavior did not show significant differences by general characteristics of the subjects except area. The subjects in the health clinic center with MCN project did better breast feeding health behavior than the subject in the health clinic center without MCN project. To raise breast-feeding rate, several strategy could be suggested. Systemic education about importance and advantages of breast-feeding and desirable breast-feeding method should be provided to pregnant women and postpartum women. Childbirth leave in the work should be prolonged, and supportive facility such as nursery room should be installed for working mothers. Hospitals should follow the guideline of 'Baby Friendly Hospital Initiative' which was provided by UNISEF and WHO, including rooming-in after delivery.

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Epidural Infusion of Morphine and Levobupivacaine through a Subcutaneous Port for Cancer Pain Management

  • Heo, Bong Ha;Pyeon, Tae Hee;Lee, Hyung Gon;Kim, Woong Mo;Choi, Jeong Il;Yoon, Myung Ha
    • The Korean Journal of Pain
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    • 제27권2호
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    • pp.139-144
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    • 2014
  • Background: To manage intractable cancer pain, an alternative to systemic analgesics is neuraxial analgesia. In long-term treatment, intrathecal administration could provide a more satisfactory pain relief with lower doses of analgesics and fewer side-effects than that of epidural administration. However, implantable drug delivery systems using intrathecal pumps in Korea are very expensive. Considering cost-effectiveness, we performed epidural analgesia as an alternative to intrathecal analgesia. Methods: We retrospectively investigated the efficacy, side effects, and complications of epidural morphine and local anesthetic administration through epidural catheters connected to a subcutaneous injection port in 29 Korean terminal cancer patients. Patient demographic data, the duration of epidural administration, preoperative numerical pain rating scales (NRS), side effects and complications related to the epidural catheterization and the drugs, and the numerical pain rating scales on the 1st, 3rd, 7th and 30th postoperative days were determined from the medical records. Results: The average score for the numerical pain rating scales for the 29 patients decreased from $7{\pm}1.0$ at baseline to $3.6{\pm}1.4$ on postoperative day 1 (P < 0.001). A similar decrease in pain intensity was maintained for 30 days (P < 0.001). Nausea and vomiting were the most frequently reported side effects of the epidural analgesia and two patients (6.9%) experienced paresthesia. Conclusions: Epidural morphine and local anesthetic infusion with a subcutaneous pump seems to have an acceptable risk-benefit ratio and allows a high degree of autonomy to patients with cancer pain.

임신 중 교통사고로 한방 치료를 받은 입원 환자에 대한 후향적 분석 (A Retrospective Analysis of Inpatients who Received Traditional Korean Medicine Treatment after a Traffic Accident during Pregnancy)

  • 윤희재;유정은
    • 대한한방부인과학회지
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    • 제34권2호
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    • pp.31-47
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    • 2021
  • Objectives: This study aimed to report the effectiveness and outcome on the prognosis of pregnancy of traditional Korean medicine treatment for inpatients who had a traffic accident during pregnancy. Methods: The study is conducted by analyzing the medical records of hospitalized patients in a Korean medicine hospital. Seventy-six pregnant patients who got into car accidents from March 2015 to February 2020 were included. We performed statistical analysis by using Statistical Package for the Social Sciences(SPSS) ver. 25.0. To verify the effect of traditional Korean medicine treatment for traffic accidents during pregnancy, we analyzed improvement of symptoms. Also, we analyzed the prognosis of pregnancy and signs of premature birth or miscarriage during treatment to verify the applicability of traditional Korean medicine treatment for traffic accidents during pregnancy. Results: Among the symptoms of pain, there was a statistically significant decrease in lower back pain, post neck pain, headache, pelvic pain, knee pain, lower limb pain, wrist pain, and upper limb pain. Other systemic symptoms showed statistically significant improvement in nausea, abdominal pain, dizziness, and lower limb numbness. All confirmed cases reported normal pregnancy maintenance and delivery, and no miscarriage was reported. Two cases that showed signs of premature birth or miscarriage during treatment were unrelated or unclear with traditional Korean medicine treatment. Conclusions: Traditional Korean medicine treatment is effective and applicable for pregnant women injured by traffic accidents. Further studies are needed to identify the effectiveness and safety of traditional Korean medicine treatment for the sequelae of traffic accidents during pregnancy.

Salmonella vector induces protective immunity against Lawsonia and Salmonella in murine model using prokaryotic expression system

  • Sungwoo Park;Eunseok Cho;Amal Senevirathne;Hak-Jae Chung;Seungmin Ha;Chae-Hyun Kim;Seogjin Kang;John Hwa Lee
    • Journal of Veterinary Science
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    • 제25권1호
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    • pp.4.1-4.14
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    • 2024
  • Background: Lawsonia intracellularis is the causative agent of proliferative enteropathy and is associated with several outbreaks, causing substantial economic loss to the porcine industry. Objectives: In this study, we focused on demonstrating the protective effect in the mouse model through the immunological bases of two vaccine strains against porcine proliferative enteritis. Methods: We used live-attenuated Salmonella Typhimurium (ST) secreting two selected immunogenic LI antigens (Lawsonia autotransporter A epitopes and flagellin [FliC]-peptidoglycan-associated lipoprotein-FliC) as the vaccine carrier. The constructs were cloned into a Salmonella expression vector (pJHL65) and transformed into the ST strain (JOL912). The expression of immunogenic proteins within Salmonella was evaluated via immunoblotting. Results: Immunizing BALB/c mice orally and subcutaneously induced high levels of LI-specific systemic immunoglobulin G and mucosal secretory immunoglobulin A. In immunized mice, there was significant upregulation of interferon-γ and interleukin-4 cytokine mRNA and an increase in the subpopulations of cluster of differentiation (CD) 4+ and CD 8+ T lymphocytes upon splenocytes re-stimulation with LI antigens. We observed significant protection in C57BL/6 mice against challenge with 106.9 times the median tissue culture infectious dose of LI or 2 × 109 colony-forming units of the virulent ST strain. Immunizing mice with either individual vaccine strains or co-mixture inhibited bacterial proliferation, with a marked reduction in the percentage of mice shedding Lawsonia in their feces. Conclusions: Salmonella-mediated LI gene delivery induces robust humoral and cellular immune reactions, leading to significant protection against LI and salmonellosis.

Mucosal Administration of Lactobacillus casei Surface-Displayed HA1 Induces Protective Immune Responses against Avian Influenza A Virus in Mice

  • Dung T. Huynh;W.A. Gayan Chathuranga;Kiramage Chathuranga;Jong-Soo Lee;Chul-Joong Kim
    • Journal of Microbiology and Biotechnology
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    • 제34권3호
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    • pp.735-745
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    • 2024
  • Avian influenza is a serious threat to both public health and the poultry industry worldwide. This respiratory virus can be combated by eliciting robust immune responses at the site of infection through mucosal immunization. Recombinant probiotics, specifically lactic acid bacteria, are safe and effective carriers for mucosal vaccines. In this study, we engineered recombinant fusion protein by fusing the hemagglutinin 1 (HA1) subunit of the A/Aquatic bird/Korea/W81/2005 (H5N2) with the Bacillus subtilis poly γ-glutamic acid synthetase A (pgsA) at the surface of Lactobacillus casei (pgsA-HA1/L. casei). Using subcellular fractionation and flow cytometry we confirmed the surface localization of this fusion protein. Mucosal administration of pgsA-HA1/L. casei in mice resulted in significant levels of HA1-specific serum IgG, mucosal IgA and neutralizing antibodies against the H5N2 virus. Additionally, pgsA-HA1/L. casei-induced systemic and local cell-mediated immune responses specific to HA1, as evidenced by an increased number of IFN-γ and IL-4 secreting cells in the spleens and higher levels of IL-4 in the local lymphocyte supernatants. Finally, mice inoculated with pgsA-HA1/L. casei were protected against a 10LD50 dose of the homologous mouse-adapted H5N2 virus. These results suggest that mucosal immunization with L. casei displaying HA1 on its surface could be a potential strategy for developing a mucosal vaccine against other H5 subtype viruses.