• Title/Summary/Keyword: Drug side effects

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Characterization of a conjugated polysuccinimide-carboplatin compound

  • Sun Young Lee;Chang Hoon Chae;Miklos Zrinyi;Xiangguo Che;Je Yong Choi;Dong-Hyu Cho
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.31-38
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    • 2023
  • Carboplatin, an advanced anticancer drug with excellent efficacy against ovarian cancer, was developed to alleviate the side effects that often occur with cisplatin and other platinum-based compounds. Our study reports the in vitro characteristics, viability, and activity of cells expressing the inducible nitric oxide synthase (iNOS) gene after carboplatin was conjugated with polysuccinimide (PSI) and administered in combination with other widely used anticancer drugs. PSI, which has promising properties as a drug delivery material, could provide a platform for prolonging carboplatin release, regulating its dosage, and improving its side effects. The iNOS gene has been shown to play an important role in both cancer cell survival and inhibition. Herein, we synthesized a PSI-carboplatin conjugate to create a modified anticancer agent and confirmed its successful conjugation. To ensure its solubility in water, we further modified the structure of the PSI-carboplatin conjugate with 2-aminoethanol groups. To validate its biological characteristics, the ovarian cancer cell line SKOV-3 and normal ovarian Chinese hamster ovary cells were treated with the PSI-carboplatin conjugate alone and in combination with paclitaxel and topotecan, both of which are used in conventional chemotherapy. Notably, PSI-carboplatin conjugation can be used to predict changes in the genes involved in cancer growth and inhibition. In conclusion, combination treatment with the newly synthesized polymer-carboplatin conjugate and paclitaxel displayed anticancer activity against ovarian cancer cells but was not toxic to normal ovarian cancer cells, resulting in the development of an effective candidate anticancer drug without severe side effects.

Formulation and Evaluation of Transdermal Patch Containing Sibutramine

  • Subedi, Robhash Kusam;Jang, Jun-Ho;Kim, Jae-Il;Park, Young-Joon;Choi, Hoo-Kyun
    • Journal of Pharmaceutical Investigation
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    • v.40 no.1
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    • pp.33-38
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    • 2010
  • Sibutramine is a serotonin-norepinephrine reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. The oral administration of sibutramine is followed by its dose-related side effects. In this study, sibutramine was formulated into drug in adhesive (DIA) patches in an attempt to overcome these problems. The effects of different formulation variables including pressure-sensitive adhesive (PSA), loading amount of drug, thickness of matrix and enhancer on the skin permeation of the drug were evaluated using excised hairless mouse skin. In the acrylic adhesive with carboxyl functional group, low release of sibutramine was observed due to the strong interaction between carboxyl group of adhesive and amine group of sibutramine. The acrylic adhesive without functional group provided good adhesion force and allowed high drug loading. Changing drug load as well as thickness of the matrix was found to alter permeation rate. $Crovol^{(R)}$ PK40 and $Crovol^{(R)}$ A40, were found to be effective enhancers for sibutramine. The optimized patch contained 20% sibutramine, and 5% $Crovol^{(R)}$ A40 as permeation enhancer, in $80\;{\mu}m$ thick Duro-$Tak^{(R)}$ 87-9301 matrix.

Stereocomplex Poly(lactic acid) Discoidal Microparticles for Sustained Drug Release (약물지연방출을 위한 스테레오컴플렉스 PLA 원반형 마이크로입자)

  • Park, Chaewon;Park, Sanghyo;Kim, Woo Cheol;Key, Jaehong
    • Journal of Biomedical Engineering Research
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    • v.41 no.1
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    • pp.62-66
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    • 2020
  • Controlled drug release is important for effective treatment of cancer. Poly(DL-lactide-co-glycolide) acid (PLGA) is a Food and Drug Administration (FDA) approved polymer and have been extensively studied as drug delivery carriers with biodegradable and biocompatible properties. However, PLGA drug delivery carriers are limited due to the initial burst release of drug. Certain drugs require an early rapid release, but in many cases the initial rapid release can be inefficient, reducing therapeutic effects and also increasing side effects. Therefore, sustained release is important for effective treatment. Poly Lactic Acid stereo complex (PLA SC) is resistant to hydrolysis and has high stability in aqueous solutions. Therefore, in this work, PLGA based discoidal polymeric particles are modified by Poly Lactic Acid stereocomplex (PLAsc DPPs). PLAsc DPPs are 3 ㎛ in diameter, also showing a relatively sustained release profile. Fluorescein 5(6)-isothiocyanate (FITC) released from PLAsc DPPs was continuously observed until 38 days, which showed the initial release of FITC from PLAsc DPPs was about 3.9-fold reduced as compared to PLGA based DPPs at 1 hour.

Combined nano-particle drug delivery and physiotherapy in treatment of common injuries in dance-sport

  • Weixin Dong;Gang Lu;Yangling Jiang;Fan Zhou;Xia Liu;Chunxia Lu
    • Advances in nano research
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    • v.15 no.3
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    • pp.225-237
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    • 2023
  • Combination of novel technologies with traditional physiotherapy in rehabilitation in injured athletes have shown to provide improved time of recovery. In specific, nanodrugs delivery systems are widely utilized as a counterpart to the physiotherapy in injuries in sports. In the present study, we focus on the common injuries in dance-sports, their recovery and the effect combination of nano-particle drug delivery with the physiotherapy practices. In this regard, a comprehensive review on the common injuries in dance sport is provided. Moreover, the researches on the effectiveness of the nano-particle drug delivery in therapy of such injuries and in similar cases are provided. The possibility of using combination of nano-particle drug delivery and physiotherapy is discussed in detail. Finally, using artificial intelligence methods, predictions on the recovery time and after-treatment side-effects is investigated. Artificial Neural Network (ANN) predictions suggested that using nano-particle drug delivery systems along with physiotherapy practices could provide shortened treatment time to recovery in comparison to conventional drugs. Moreover, the post-recover effects are less than the conventional methods.

Silibilin-Induces Apoptosis in Breast Cancer Cells by Modulating p53, p21, Bak and Bcl-xl Pathways

  • Pirouzpanah, Mohammad Bagher;Sabzichi, Mehdi;Pirouzpanah, Saeed;Chavoshi, Hadi;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.2087-2092
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    • 2015
  • Nowadays herbal-derived medicines are attracting attention as new sources of drugs with few side effects. Silibinin is a flavonoid compound with chemotheraputic effects on different cancers such as examples in the prostate, lung, colon and breast. In the present study, the cytotoxic effects of silibinin on MCF7 breast cancer cells were investigated. Apoptosis was determined by flow cytometry and the impact of silibinin on the expression of pivotal genes including Bak, P53, P21, BRCA1, BCL-X1 and ATM was analyzed. Treatment for 24h had a significant dose-dependent inhibitory effect on cell growth (p<0.05) with dose- and time- dependent induction of apoptosis (p<0.05). In addition, there were significant increases in BRCA1, ATM, Bak and Bcl-XL gene expression at the mRNA level with different concentrations of silibinin for 24 or 48 h (p<0.05). Taken together, the results suggest that silibinin inhibits the proliferation and induces apoptosis of MCF-7 cells by down-regulating Bak, P53, P21, BRCA1, BCL-Xl and thus may be considered as an effective adjuvant drug to produce a better chemopreventive response for the cancer therapy.

Experiences of Treatment-Related Side Effects and Supportive Care with Korean Medicine in Women with Breast Cancer - A Focus Group Study (유방암 환자의 항암 치료 부작용 및 한의학적 보완치료 경험에 관한 포커스 그룹 연구)

  • Han, Sola;Jang, Bo-Hyoung;Hwang, Deok-Sang;Suh, Hae Sun
    • The Journal of Korean Obstetrics and Gynecology
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    • v.30 no.1
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    • pp.85-94
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    • 2017
  • Objectives: To explore experiences of treatment-related side effects and supportive care among Korean breast cancer survivors (BCS). Methods: Focus group interview was conducted with six Korean women with breast cancer. Participants were recruited through snow-balling. Interview was audio-recorded and transcribed verbatim. NVivo-11 was used to code the data into themes. Results: Two major themes were identified: (1) experiences of Western medicine, including treatment, side effects, needs and costs; (2) experiences of supportive care with Korean medicine, including the same as above. All participants experienced Western medicine in treatment phase and reported impairment of physical, emotional, and social functioning during and after Western medicine treatment. Only three participants used Korean medicine after treatments end. The negative responses from Western medicine doctors were the most important factor keeping participants from accessing Korean medicine when treatment-related side effects occurred. For this reason, some participants used Korean medicine without disclosure. Participants usually acquired information about Korean medicine from online community or other BCS, which was another important factor because it raised concerns about side effects and credibility of Korean medicine. High cost was also reported as barrier in using Korean medicine. During the cancer treatment, participants tended to endure their treatment-related side effects. Conclusions: Korean BCS may be at high risk of physical or emotional distress during treatment period. Findings suggest that there is a high need for supportive care to relieve treatment-related side effects and improve patients' quality-of-life. Furthermore, developing a systematic guidance or credible information sources should be warranted to help patients find the best supportive care options including Korean medicine.

Development of Polymeric Nanopaclitaxel and Comparison with Free Paclitaxel for Effects on Cell Proliferation of MCF-7 and B16F0 Carcinoma Cells

  • Yadav, Deepak;Anwar, Mohammad Faiyaz;Garg, Veena;Kardam, Hemant;Beg, Mohd Nadeem;Suri, Suruchi;Gaur, Sikha;Asif, Mohd
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2335-2340
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    • 2014
  • Paclitaxel is hydrophobic in nature and is recognized as a highly toxic anticancer drug, showing adverse effects in normal body sites. In this study, we developed a polymeric nano drug carrier for safe delivery of the paclitaxel to the cancer that releases the drug in a sustained manner and reduces side effects. N-isopropylacrylamide/vinyl pyrrolidone (NIPAAm/VP) nanoparticles were synthesized by radical polymerization. Physicochemical characterization of the polymeric nanoparticles was conducted using dynamic light scattering, transmission electron microscopy, scanning electron microscopy and nuclear magnetic resonance, which confirmedpolymerization of formulated nanoparticles. Drug release was assessed using a spectrophotometer and cell viability assays were carried out on the MCF-7 breast cancer and B16F0 skin cancer cell lines. NIPAAm/VP nanoparticles demonstrated a size distribution in the 65-108 nm range and surface charge measured -15.4 mV. SEM showed the nanoparticles to be spherical in shape with a slow drug release of ~70% in PBS at $38^{\circ}C$ over 96 h. Drug loaded nanoparticles were associated with increased viability of MCF-7 and B16F0 cells in comparison to free paclitaxel. Nano loaded paclitaxel shows high therapeutic efficiency by sustained release action for the longer period of time, i increasing its efficacy and biocompatibility for human cancer therapy. Therefore, paclitaxel loaded (NIPAAm/VP) nanoparticles may provide opportunities to expand delivery of the drug for clinical selection.

Thermographic Changes by Administering Gabapentin in Neuropathic Pain -A report of three cases- (신경병증성 통증 치료시 Gabapentin 투여에 따른 제통 효과와 체열상의 변화 -증례 보고-)

  • Lee, Jang-Won;Kim, Jung-Soon;Bae, Duck-Ku;Park, Wook
    • The Korean Journal of Pain
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    • v.14 no.1
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    • pp.98-103
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    • 2001
  • Neuropathic pain originating from multiple condition of nerve cell injury is common, but is difficult to treat. Even though many drugs such as anti-convulsants, anti-depressants, NSAIDs, opioids have been used, their clinical analgesic action were not satisfactory due to occur severe side effects. Gabapentin was introduced in 1994 as a novel antiepileptic drug and has been used to treat partial seizure. After 1995 gabapentin treatment for reflex sympathetic dystrophy (RSD) started, 45% of the reports about the analgesic efficacy of gabapentin were restricted to the treatments of non-epileptic pain syndrome. This drug is preferred to treat neuropathic pain because of a lower incidence of its side effects than those of other anti-convulsants and anti-depressants. For evaluating it's analgesic efficacy, the changes in the patients' subjective pain intensity was measured by the score on the visual analogue scale (VAS) and patient's objective pain intensity by measuring the skin temperature via infrared thermography were investigated respectively. Side effects of gabapentin were look into. We observed successful relief of neuropathic pain in the three patients which included post-herpetic neuraligia, complex regional pain syndrome (CRPS) and diabetic neuropathic pain, and the side effects of gabapentin were at acceptable levels.

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Antiarrhythmic effects of ginsenoside Rg2 on calcium chloride-induced arrhythmias without oral toxicity

  • Gou, Dongxia;Pei, Xuejing;Wang, Jiao;Wang, Yue;Hu, Chenxing;Song, Chengcheng;Cui, Sisi;Zhou, Yifa
    • Journal of Ginseng Research
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    • v.44 no.5
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    • pp.717-724
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    • 2020
  • Background: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca2+/calmodulin-dependent protein kinase II. Conclusion: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.

A Review on Experimental Research about Anticancer Drug Combined Treatment with Herbal Medicine for Killing or Inhibiting Proliferation of Cancer cells in Korea. (항암제와 한약재의 병용투여 시 암세포 증식억제 효과에 대한 국내 실험연구 문헌고찰)

  • Lee, Ji Eun;Choi, Jin Yong;Han, Chang Woo;Choi, Jun Yong;Park, Seong Ha;Kim, So Yeon
    • Herbal Formula Science
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    • v.25 no.3
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    • pp.391-412
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    • 2017
  • Objective : In this study, we searched the experimental research about combined treatment of anticancer drug and herbal medicine for killing or inhibiting proliferation of Cancer cells searched in OASIS and KISS. This study aimed to analyze the experimental research paper about anticancer drug combined treatment with herbal medicine. Methods : We collected the research paper including killing or inhibiting proliferation of Cancer cells in OASIS and KISS using keyword anticancer drug with herbal medicine, tumor suppressor with herbal medicine, inhibition of Cancer with herbal medicine and combined treatment with herbal medicine. Assorting by cancer cells, we analyzed experimental results cancer cell viability, anticancer drug dosage, tumor weight and survival rate. Also, we checked the effects of herbal medicine on cancer and additive effect reducing side effect of anticancer drug. Results : Total 45 studies were selected. 38 studies reported combined treatment of anticancer drug and herbal medicine was more effective than only anticancer drug. The death of cancer cells was synergistically induced by the cotreatment of anticancer drug and herb extracts. The studies suggest that the cotreatment of anticancer drug and herb extracts could reduce side effect of anticancer drug. In addition, some studies reported cotreatment mechanism like apoptotic death signal processes. In combined treatment of anticancer drug and herb extracts, The expression of Fas/Fas L, Bax, Bcl2, Caspase-3 etc.. was markedly increased in cancer cells. Conclusions : Our results suggest that anticancer drug combined treatment with herbal medicine could be efficient for killing or inhibiting proliferation of cancer cells. However, this paper had some limitation as follows: First, collected studies have been published only for korean journal. Second, results of research and effects of combined treatment are not collected objectively. To solve these problems, more objective and balanced studies should be performed.