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The Evaluation of The Use of Dependency Substances During Pregnancy
Ayçe ÇELİKER*º , Damla BOLAT**
* ORCID NO: 0000-0001-6753-6844, Department of Clinical Pharmacy, Faculty of Pharmacy, Hacettepe University, Ankara, 06100
** ORCID NO: 0000-0003-3824-3393, Department of Pharmaceutical Technology-Cosmetology, Faculty of Pharmacy, Hacettepe University, Ankara, 06100
º Corresponding Author: Ayçe ÇELİKER
Tel: 0312-305 21 33, Fax: 0312-305 20 39, e-mail: aycelike@hacettepe.edu.tr
SUMMARY
Substance dependency is an increasingly important problem throughout the world. Alcohol and cigarette addiction, as well as the use of narcotics and stimulants have increased very seriously. Individuals using these substances cause serious harm to themselves and their environment. The use of such substances during pregnancy adversely affects maternal health and the development of the fetus. Substance-dependent women do not get checked their examinations regularly during pregnancy and substance abuse can be realized at the final stage of the pregnancy. For this reason, health care personnel should be able to identify, guide and educate pregnant women who use drugs, especially focusing on those that abusers of drugs and other substances, so that the negative effects of the substance(s) on the mother, fetus and newborn can be minimized. In this study, the structures, general characteristics, metabolisms, and impacts on the fetus of illicit and abused substances in Turkey were compiled. Besides, the role of pharmacists in prevention and management of substance dependency was emphasized.
Key Words: Illegal substance, addiction, abuse, recreational, pregnancy, teratogenicity.
Use of Herbal Products in Lactation
Ayperi PAYAS* , Ayçe ÇELİKER**º
* ORCID NO: 0000-0002-6625-7947, Department of Clinical Pharmacy, Faculty of Pharmacy, Hacettepe University, Ankara,
** ORCID NO: 0000-0001-6753-6844, Department of Clinical Pharmacy, Faculty of Pharmacy, Hacettepe University, Ankara,
º Corresponding Author: Ayçe ÇELİKER
Phone: 0312-305 21 33, Fax: 0312-305 20 39, e-mail: aycelike@hacettepe.edu.tr
SUMMARY
Recently, usage of herbs and herbal products have gain popularity for several indications. The reason of the popularition of these products could be the thoughts of the people which natural products are much less harmful. With this point of view breastfeeding mothers are commonly using herbal products to raise their milk production (galactagogue) or treat post-natal diseases. But, there are big threats for both mother and baby in some issues such as the efficiency of herbal products, their toxicities, lack of scientific studies evaluating the effects on the baby, the large numbers of bioactive components and unavailability of convenient regulations. The aim of this review is to provide a guide about safety of popular herbal products commonly used by breastfeeding mothers and their effects on infants; to health care providers, such as pharmacists, who are the closest health advisors of patients, as well as physicians, and nurses and to ensure the careful use of herbal products in order to avoid undesirable effects by raising awareness that the word of “natural” is not synonymous with “safe”.
Key Words: Herb, herbal product, breastfeeding, lactation, galactagogue, safety.
Interactions between Warfarin and Herbal Products: Case reports, Preclinical and Clinical Studies
İçim GÖKKAYA* , Tuğba SUBAŞ** , Gülin RENDA***° , Ufuk ÖZGEN****
* ORCID: 0000-0003-0803-2886, Karadeniz Teknik Üniversitesi Eczacılık Fakültesi, Farmakognozi ABD, Trabzon, TÜRKİYE
** ORCID: 0000-0002-0956-6567, Karadeniz Teknik Üniversitesi Eczacılık Fakültesi, Farmakognozi ABD, Trabzon, TÜRKİYE
*** ORCID: 0000-0001-6323-0338, Karadeniz Teknik Üniversitesi Eczacılık Fakültesi, Farmakognozi ABD, Trabzon, TÜRKİYE
**** ORCID: 0000-0001-9839-6717, Karadeniz Teknik Üniversitesi Eczacılık Fakültesi, Farmakognozi ABD, Trabzon, TÜRKİYE
º Corresponding Author: Gülin RENDA
Phone: 04623778830 – 05323331133; e-mail: gulingurhan@yahoo.com
SUMMARY
Plants have been used in the prevention and treatment of diseases since ancient times. Due to the popularity and unconscious use of herbal products, the risk of health problems is increasing day by day. Simultaneous use of herbal products especially with drugs having narrow therapeutic index can lead to very serious toxic effects. Warfarin, which is used to treat or prevent atrial fibrillation, venous thromboembolism, deep vein thrombosis, pulmonary embolism, artificial heart valve and myocardial infarction, acts as an anticoagulant by blocking the epoxide reductase enzyme and inhibiting the conversion of vitamin K and vitamin K epoxide. Warfarin is rapidly absorbed from the gastrointestinal tract, has high bioavailability and reaches the maximum concentration in blood plasma after 90 minutes orally and is therefore widely used in the clinic. Warfarin has the potential to interact with many drugs, herbal products and foods, and it has been reported that it is the drug that causes the most frequent plant-drug interactions. In this study, case reports of warfarin-herb interaction in the literature were examined and the herb/herbal product used by the patient, drugs used by the patient other than warfarin, and the clinical symptoms related to the interaction were compiled. In addition, in vivo, in vitro, and clinical studies conducted on plants reported to be interacting in case reports were investigated, and the results obtained regarding the herbal products, dose, duration of use, study type, warfarin dose, and interaction mechanism were presented. Herbal products cause an interaction by inducing or inhibiting CPY2C9, CYP3A4, and CYP1A2 enzyme activities as well as P-glycoprotein, which play a role in warfarin metabolism. The responsibility of healthcare professionals and the importance of selling herbal products under the consultancy of healthcare personnel is emerging in preventing possible adverse drug reactions and toxic effects and ensuring rational drug use.
Key Words: Warfarin, drug-herb interactions, drug-food interactions, P-glycoprotein, rational drug use, herbal product.
Design of Tyrosine Kinase Inhibitory Compounds and Anticancer Mechanisms of Action
Süreyya ÖLGENº* , Ahmet Mesut ŞENTÜRK**
* ORCID: 0000-0002-0725-8413, Biruni Üniversitesi Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, 10. Yıl Cad. No:45 Topkapı/ İSTANBUL
** ORCID: 0000-0001-6818-6161, Biruni Üniversitesi Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, 10. Yıl Cad. No:45 Topkapı/ İSTANBUL
º Corresponding Author: Süreyya Ölgen
Tel: 444 8 276, Fax: 90 212 416 46 46, e-mail: solgen@biruni.edu.tr
SUMMARY
Cancer is a complex disease that is caused by uncontrolled division and proliferation of cells and under the influence of genetic and conditions. There are more than 100 types of cancers known and standardized therapies to certain types of cancers as much as possible have been developed. The DNA of any human on Earth is not alike. Therefore, patients provide different responses to similar treatments. Tyrosine kinases (TKs) are a family of enzymes involve the signal transduction in human cell. TKs are essential needs for normal human physiology. Destruction of normal functions cause abnormal cell activities, immunological, neurological, metabolic and infectious diseases, especially cancer. Among the kinases, Abelson Leukemia (Abl), sarcoma (Src), epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are primary molecular targets for selective inhibition and are considered the most successful targeted therapy for tyrosine kinase inhibitors (TKIs). Today, there are many Food and Drug Administration approved TKIs, which are frequently used in cancer treatment. In this review, the design strategies of the compounds as TKIs, the structure-protein interaction relationships, the functional role of the kinases targeted in the inhibitor design, the structural analysis of the binding modes of the kinase inhibitors, and the current developments in the therapeutic interventions of tyrosine kinase inhibitors have been discussed.
Key Words: Cancer, inhibitor design, TKIs, structural analysis, selectivity, specifity.
Hydroxychloroquine: Similarity Search and Structure- Based Virtual Screening for Identification of Potential Hits for Chemoprophylaxis Against SARS-CoV-2
Shravan Kumar PASWAN°*† , Virendra NATH***† , Pritt VERMA** , Arun Pratap SIKARWAR**** , Sudhir K. VERMA*****
* ORCID: 0000-0002-2729-6257, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India
** ORCID: 0000-0003-1433-2623, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India
*** ORCID: 0000-0003-1367-7144, Central University of Rajasthan, Ajmer, India
**** ORCID: 0000-0001-5322-3951, Department of Zoology, Dayalbagh Educational Institute, Agra, Uttar Pradesh, India
***** ORCID: 0000-0002-7713-2250, Department of Chemistry, Dayalbagh Educational Institute, Agra, Uttar Pradesh, India
† Equally contributed authors
° Corresponding Author; Shravan Kumar PASWAN
e-mail: paswanshravan@gmail.com
SUMMARY
The current eruption of the novel severe acute respiratory syndrom causing coronavirus 2 (SARS-CoV-2) is an atrocious health tragedy. In this virulent disease, the computational approach appears to be the most hopeful choice to make out an efficient remedial medicinal agent for the treatment of an infected population. This current exploration inclined to analyze the similar druggable compounds as hydroxychloroquine to combat unworn coronavirus (COVID-19), using a pharmacoinformatics study. Docking-based virtual screening was carried-out using Glide, followed by Absorption Distribution Metabolism Excretion (ADME) anticipation. Hydroxychloroquine is being used as the criterion for comparison as it showed potential effect for symptomatic relief. Target-based virtual screening study divulged 28 top-ranked compounds based on their binding energy and dock score from 10695 PubChem compounds. In the additional weed-out process, 07 compounds were selected based on their similar interactions as hydroxychloroquine, comparable binding energy, and shape complementarity of the binding pocket of 6LU7. The
three-dimensional binding pose of screened 07 hits and their chemoessential features were successfully matched with reference compound. These candidates showed potential interactions with the amino acid residues of the active site of SARS-CoV-2 (PDB ID 6LU7). Therefore, they may have the capability as lead compound(s) against COVID-19.
Key Words: Binding energy, COVID-19, Docking,Hydroxychloroquine, SARS-CoV-2, Virtual Screening
Investigation of GSTM1 and GSTT1 Polymorphisms in Obesity Patients Under Bariatric Surgery
Abdulkadir Ünsal* , Hakan Buluş** , Onur Dirican*** , Serpil Oğuztüzün**** , Doğan Öztürk***** , Mehmethan Cihan****** , Ahmet Oğuz Ada******* , Mümtaz İşcan********
* ORC ID: 0000-0002-7989-4232, University of Health Sciences; Keçiören Training and Research Hospital; General Surgery Department; Ankara/Turkey
** ORC ID: 0000-0001-7439-8099, University of Health Sciences; Keçiören Training and Research Hospital; General Surgery Department; Ankara/Turkey
*** ORC ID: 0000-0003-0511-6611, Kırıkkale University Faculty of Science; Department of Biology; Kırıkkale/Turkey
**** ORC ID: 0000-0002-5892-3735, Kırıkkale University Faculty of Science; Department of Biology; Kırıkkale/Turkey
***** ORC ID: 0000-0003-1754-9246, University of Health Sciences; Keçiören Training and Research Hospital; General Surgery Department; Ankara/Turkey
****** ORC ID: 0000-0001-8701-754X, University of Health Sciences; Keçiören Training and Research Hospital; General Surgery Department; Ankara/Turkey
******* ORC ID: 0000-0001-9987-0572, Ankara University Faculty of Pharmacy Department of Toxicology; Ankara/Turkey.
******** ORC ID: 0000-0001-5839-4987, Cyprus International University, Faculty of Pharmacy, Lefkoşe, Turkish Republic of Northern Cyprus.
° Corresponding Author; Hakan BULUŞ
Tel.: +90-312 356 90 00 / 1158, e-mail : hakan_bulus6@hotmail.com
SUMMARY
Obesity is a chronic disorder with increasing prevalence worldwide and occurs when energy intake is more than energy expenditure. Obesity is one of the factors that cause oxidative stress and arises from an imbalance between the reactive oxygen species ROS and the cell’s antioxidant defense system. Increasing ROS in obesity, influencing the hypothalamic neurons, affect hunger and satiety control, so correspondingly on body weight control. When ROS amount increases, through DNA, protein, and lipid oxidation, cell damage, necrosis, and apoptosis take place. Oxidative stress increment in adipose tissue causes the development of metabolic syndrome in obese people. Also, weight loss due to calorie restriction or exercise reduces oxidative stress. Mitochondria is the essential source for ROS formation. In the electron transfer system, reactive oxygen species forming due to oxidative phosphorylation reactions are involved in various physiological processes such as cell proliferation and differentiation. Glutathione S-transferase M1 and T1 genes encode enzymes that have oxidant-scavenging activities. Deletion polymorphisms in these genes cause the absence of their corresponding enzymes. In this study, we investigated the parameters associated with obesity such as body mass index (BMI), TSH, glucose, satiety blood glucose, triglyceride,
and cholesterol levels, and deletion polymorphisms of GSTM1 and GSTT1 genes in 152 patients diagnosed with obesity in a Turkish population. No statistically significant relationship was found
between the parameters studied in obese patients and GSTM1 and GSTT1 polymorphisms. More studies are needed to elucidate the relationship of GSTM1 and GSTT1 polymorphisms with obesity.
Key Words: Obesity, GSTM1, GSTT1, Oxidative stress, Polymorphism, Multiplex PCR.
Rice Bran Supplement Enhances GSH Levels in Testis and Liver of Carbon Tetrachloride-induced Rats
Dwirini Retno Gunarti* , Dewi Sukmawati** ° , Mochammad Kamal Nasser*** , Teuku Abdi Zil Ikram**** , Rizqi Nanda Pribawa***** , Dwi Anita Suryandari******
* ORCID ID: 0000-0002-1990-0098, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
** ORCID ID: 0000-0003-3777-8118, Department of Histology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
*** ORCID ID: 0000-0002-9895-8019, Undergraduate student, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
**** ORCID ID: 0000-0003-1109-4893, Undergraduate student, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
***** ORCID ID: 0000-0002-0984-925X, Undergraduate student, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
****** ORCID ID: 0000-0003-2711-8335,Department of Medical Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
° Corresponding Author; Dewi Sukmawati, MD., Ph.D.
Phone: +62 21 3146129, e-mail: ds_histoui@outlook.com; dewi.sukmawati@ui.ac.id
SUMMARY
In the present study, the potency of rice bran as an antioxidant was examined. Rice bran is a by-product of the rice milling process, despite being a rich nutrient, it has limitations in food application. In this study, we used carbon tetrachloride-induced rats (CCl4) as a model of oxidative stress and examined the effect of extract IPB 3S rice bran supplement (RBS) on testis and liver endogenous antioxidant. The testis and liver were used as the representative organs which prone to exposure to reactive oxygen species (ROS). We used 150 and 300 mg.kg-1 Body weight (BW) of RBS. The Concentration of glutathione (GSH) in both organs was measured. All groups administered by RBS had significantly higher GSH levels compared to the CCl4 group, both in testis and liver. The dose of 300 mg.kg-1 BW RBS had a significantly higher GSH level in testis, while 150 mg.kg-1 VA RBS had a significantly higher GSH level in the liver tissue compared to the control group accordingly. Thus, the rice bran supplement enhances GSH levels in rat’s liver and testis which potentially has protective effects.
Key Words: Rice bran, IPB 3S, antioxidants, glutathione, CCl4, liver, testis.
Protective Effects of Ferulic Acid Against Isoniazid-Induced Hepatotoxicity in Rats
Ahmad AHMADIPOUR* , Fariba SHARIFIFAR** , Hussein ANANI*** , Somayyeh KARAMI-MOHAJERI****°
* ORCID: 0000-0001-7987-3872 Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran,
** ORCID: 0000-0003-1792-3760 Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran,
*** ORCID: 0000-0002-4770-3008 Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran,
**** ORCID: 0000-0001-6256-6550 Department of Pharmacology and Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran,
° Corresponding Author; Somayyeh KARAMI-MOHAJERI,
Tel: +98 34 31325239, Fax: +98 34 31325003, e-mail: s_karami@kmu.ac.ir
SUMMARY
Isoniazid (INH) is an antibiotic that is used for the prevention and treatment of tuberculosis. The most common side effect of INH is seemingly hepatotoxicity through the induction of oxidative damage. Ferulic acid (FA) is an organic compound with antioxidant properties that is found abundantly in plant cell walls. The aim of this study was to evaluate the hepatoprotective effects of FA against hepatotoxicity induced by INH in Wistar rats. The rats were injected with INH (100 mg/kg/d for 21 days) with and without co-administration of FA (10 and 20 mg/kg/d) or silymarin (100 mg/kg/d) from day 11 to day 21. Then, the animals were sacrificed to evaluate the serum levelof aminotransferases and total bilirubin, and liver histopathology and oxidative stress parameters. Co-administration of FA prevented the hepatotoxicity of INH according to the biochemical and histology findings. FA dose-dependently decreased level of lipid peroxidation in liver tissue. The activities of catalase, superoxide dismutase, and glutathione peroxidase in liver tissues of rats treated with FA were higher than those in non-treated INH-exposed rats. Taken together,
the results demonstrated that FA could be used as a hepatoprotective supplement to prevent INH-induced hepatotoxicity.
Key Words: Isoniazid, ferulic acid, hepatotoxicity, antioxidant, oxidative stress, histopathology.
Morphological Investigations on the Diagnostic Features of Six Hypericum Species of the Ukrainian Flora
Valentyna MINARCHENKO* , Oksana FUTORNA** , Vitalii PIDCHENKO***° , Iryna TYMCHENKO**** , Tetyana DVIRNA***** , Larysa MAKHYNIA******
* ORCID: 0000-0002-5049-7620, M.G. Kholodny Institute of Botany, National Academy of Sciences of Ukraine 2 Tereshchenkivska Str., Kyiv 01004, Ukraine;
O.O. Bogomolets National Medical University. 22 Pushkinska Str., Kyiv 01004, Ukraine
** ORCID: 0000-0002-3713-6644, M.G. Kholodny Institute of Botany, National Academy of Sciences of Ukraine 2 Tereshchenkivska Str., Kyiv 01004, Ukraine
*** ORCID: 0000-0003-0850-6666, O.O. Bogomolets National Medical University. 22 Pushkinska Str., Kyiv 01004, Ukraine
**** ORCID: 0000-0001-7505-3164, M.G. Kholodny Institute of Botany, National Academy of Sciences of Ukraine 2 Tereshchenkivska Str., Kyiv 01004, Ukraine
***** ORCID: 0000-0002-9279-9766, M.G. Kholodny Institute of Botany, National Academy of Sciences of Ukraine 2 Tereshchenkivska Str., Kyiv 01004,
Ukraine; O.O. Bogomolets National Medical University. 22 Pushkinska Str., Kyiv 01004, Ukraine
****** ORCID: 0000-0002-8095-4255, O.O. Bogomolets National Medical University. 22 Pushkinska Str., Kyiv 01004, Ukraine
° Corresponding Author: Vitalii Pidchenko
Phone: +380937670224; e-mail: pidchenkovitalii@gmail.com
SUMMARY
The results of comparative analysis of the main diagnostic features of the medicinal raw material of six species of the genus Hypericum of Ukraine are presented. The most important diagnostic features of H. alpigenum Kit, H. elegans Steph. ex Willd., H. hirsutum L., H. maculatum Crantz, H. montanum L., and H. perforatum L. are the localization, form, and color of secretory structures. Characteristics of the basic morphological features of leaves, sepals, petals, and stems of the studied species are provided. It is emphasized that a comprehensive analysis of the species-specific peculiarities of the main raw organs of species of the genus Hypericum allows us to determine their species affiliation clearly. The use of these features makes it impossible to intentionally falsify or incorrectly identify the raw material of a particular species of St. John’s worth during merchandising analysis.
Key Words:
Diagnostic features, Hypericum, medicinal raw materials, leaves, sepals, petals, stems, secretory structures, Ukraine
Enhancing Skin Penetration: The Role of Microneedles
Bülent SAMANCI*º , Fatma Gülgün YENER** , İsmail Tuncer DEĞİM***
* ORCID: 0000-0002-7198-5375, Pharmaceutical Technology Department, Faculty of Pharmacy, Dicle University, Diyarbakir, Turkey,
** ORCID: 0000-0002-7234-0034, Proffesor, Pharmaceutical Technology Department, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey
*** ORCID: 0000-0002-9329-4698, Proffesor, Pharmaceutical Technology Department, Faculty of Pharmacy, Biruni University, Istanbul, Turkey
º Corresponding Author: Bülent SAMANCI
Phone: +904122411000-7531; e-mail: bulent.samanci@dicle.edu.tr
SUMMARY
Since transdermal delivery systems provide some important advantages over oral delivery systems and parenteral delivery systems, they have attracted the attention of researchers. Degradation of the drug in the gastrointestinal (GI) system, irritation of the GI system tract, and the first-pass effect of the drug are some of the disadvantages of oral administration, while the need for medical staff to administer it and creating phobia in the patient are among the disadvantages of parenteral administration. To overcome these drawbacks, researchers have developed formulations for the transdermal delivery of drugs. The most important handicap of transdermal drug administration is the Stratum Corneum layer (St. Corneum), which forms the enormous barrier layer of the skin. Some techniques have been developed to overcome this serious barrier problem of the skin. Microneedles are one of the physical methods to increase the penetration of therapeutic agents through the skin. Microneedles consist of needle arrays long enough to deliver the drug to the dermis layer and micron-sized enough to not reach the nerve cells and not cause pain. Microneedles can
be classified into five different types as solid microneedles, dissolving microneedles, hollow microneedles, coated microneedles, and hydrogel microneedles according to the properties of the materials used in the fabrication and the mechanisms of release of the therapeutic agent. Microneedles can be used in the application of vaccines, proteins, nucleotides, drug delivery systems, cosmetic, and for diagnostic purposes. Although important technological developments have been experienced for microneedle in many areas such as drug delivery systems, disease diagnosis, and cosmetics in the last two decades, there are many working areas that need to be developed. Especially in longterm treatments, studies should be done to develop them as smart devices.
Key Words:
Drug Delivery, Intradermal, Microfabricated device, Microneedle, Skin Penetration, Transdermal.
Therapeutic Applications of Radiopharmaceuticals: An Overview
Erol AKGUN*, Emre OZGENC**º , Evren GUNDOGDU***
** ORCID NO: 0000-0002-7586-8520, Department of Radiopharmacy, Faculty of Pharmacy, Ege University, Izmir, Turkey
*** ORCID NO: 0000-0003-2111-101X, Department of Radiopharmacy, Faculty of Pharmacy, Ege University, Izmir, Turkey
º Corresponding Author: Emre ÖZGENÇ
Phone: 232 311 3282; e-mail: emre.ozgenc@ege.edu.tr
SUMMARY
Radiopharmaceuticals are radioactive medications (radioisotopes) and are composed of radionuclidic and pharmaceutical parts. Recently, the use of radiopharmaceuticals as diagnostic and therapeutic agents is increasing. Several approaches have been employed to develop therapeutic radiopharmaceuticals. Therapeutic radiopharmaceuticals have essential roles in nuclear medicine administrations. Today, various diseases such as thyroid cancer, metastatic bone cancer, neuroendocrine tumors, and myeloproliferative can be treated with radioimmunotherapy. These treatments provide convenience in multiple ways and can be advantageous compared to other treatment methods. In this review, current radiopharmaceuticals and their usage in different disease treatments are summarized by providing fine details. Also, the definition of theranostics is summed up. In conclusion, this review can be beneficial for scientists who work in this area.
Key Words:
Radiopharmaceutical, Treatment, Nuclear Medicine, Radionuclide, Radioimmunotherapy, Theranostics.
The Effects of Combination Therapy of Ionizing Radiation and Oncolytic Viruses
Meliha EKİNCİ* , Derya İLEM-ÖZDEMİR**º
* ORCID: 0000-0003-1319-3756, Ege Üniversitesi, Eczacılık Fakültesi, Radyofarmasi Anabilim Dalı, 35100 Bornova, İzmir, Türkiye.
** ORCID: 0000-0002-1062-498X, Ege Üniversitesi, Eczacılık Fakültesi, Radyofarmasi Anabilim Dalı, 35100 Bornova, İzmir, Türkiye.
º Corresponding Author: Derya İLEM-ÖZDEMİR
Tel: 232 311 3282; e-mail: deryailem@gmail.com
SUMMARY
Cancer is the leading cause of death worldwide. Treatment methods in cancer consist of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Ionizing radiation therapy, which deprives cancer cells of its ability to reproduce, remains an important component of cancer treatment, with about 50% of all cancer patients receiving radiation therapy during the disease, and contributes to 40% of curative treatment for cancer. Due to the side effects of these routine cancer treatments, the need for new therapeutic strategies has increased. With the development of oncolytic viruses in the last 20 years, a new area called virotherapy has been created in the treatment of cancer. Oncolytic viruses are a new biological therapeutic group with a wide spectrum of anticancer activity, with low human toxicity. Studies have shown that oncolytic viruses, which can be designed to selectively infect and / or multiply in cancer cells, have an increased antitumoral effect on tumor xenografts combined with ionizing radiation. In this review, treatment methods with ionizing radiation and oncolytic viruses are described and examples from current studies are presented.
Key Words:
Ionizing radiation, oncolytic virus, cancer, therapy, virotherapy, xenografts.
Printers and Printing Technologies in the Pharmaceutical Field
Ece ÇOBANOĞLU* , Cem VARAN** , Erem BİLENSOY***º
* ORCID: 0000-0002-4804-7495, Mersin Üniversitesi, Farmasötik Biyoteknoloji Anabilim Dalı, 33169 – Mersin
** ORCID: 0000-0002-9391-8691, Hacettepe Üniversitesi, Farmasötik Teknoloji Anabilim Dalı, 06100 - Ankara
*** ORCID: 0000-0003-3911-6388, Hacettepe Üniversitesi, Farmasötik Teknoloji Anabilim Dalı, 06100 - Ankara
º Corresponding Author: Erem Bilensoy
Tel: 0312 305 43 69; E-mail: eremino@hacettepe.edu.tr
SUMMARY
Currently, the importance of personalized medicine and the widespread use of 3D production techniques in almost all industrial fields, pave the way for the preparation of personalized and customizable pharmaceutical dosage forms with 3D printers. New 3D production techniques are developed and their applicability to the pharmaceutical industry is being investigated day by day. This review is aimed to evaluate printing technologies, which will play an important role in future pharmaceutical manufacturing along with a detailed review of publications about 2D and 3D printing techniques. Within the scope of the review, printing techniques were compared with each other from a pharmaceutical and biomedical perspective, and possible predictions about how an ideal production method were discussed by revealing the possible advantages and disadvantages of these innovative techniques.
Key Words:
2D Printer, 3D Printer, Drug, Personalized Medicine, Pharmaceutics, Printing Technology
Bioactivities of A Major Compound from Arthrinium rasikravindrae An Endophytic Fungus of Coleus amboinicus Lour.
Puji ASTUTI°* , Dwi Koko PRATOKO** , Rollando ROLLANDO*** , Giri Wisnu NUGROHO**** , Subagus WAHYUONO***** , Triana HERTIANI****** , Arief NURROCHMAD*******
* ORCID: 0000-0003-3316-6149, Pharmaceutical Biology Department, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia 55281
** ORCID: 0000-0001-7262-4515, Faculty of Pharmacy, Universitas Jember, Jember, Indonesia
*** ORCID: 0000-0001-6210-6247, Program of Pharmacy, Faculty of Science and Technology, Ma Chung University, Malang, Indonesia
**** ORCID: 0000-0001-9086-3181, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia 55281
***** ORCID: 0000-0002-1374-4506, Pharmaceutical Biology Department, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia 55281
****** ORCID: 0000-0002-1756-2478, Pharmaceutical Biology Department, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia 55281
******* ORCID: 0000-0001-7597-2574, Pharmacology and Clinical Pharmacy Department, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
°Corresponding author: Puji Astuti
Phone/Fax: +62-274-543120; e-mail: puji_astuti@ugm.ac.id
SUMMARY
Many studies reported the ability of endophytic fungi to produce various bioactive compounds having therapeutic values. An endophytic fungus identified as Arthrinium rasikravindrae was isolated from the stem of Coleus amboinicus Lour. This study examined cytotoxic and antimicrobial activities of a major compound isolated from ethyl acetate extract of the fungus fermentation broth. Cytotoxic activities were conducted using MTT assay against T47D, MCF-7, WiDr, 3T3, and Vero cells. IC50 values against Staphylococcus aureus and Escherichia coli were used as the parameters for determining antimicrobial activities. The isolated compound appeared as a single peak in HPLC chromatogram (98.55 %), displayed the highest cytotoxic activity on WiDr cells (IC50 35.03 ± 2.08 μg/mL) and antimicrobial activities against S. aureus (IC50 232.10 ± 1.20 μg/mL) and E. coli (243.59 ± 1.32 μg/mL). Analysis of the UV spectrum and TLC data generated by various detection reagents revealed that the compound was predicted as an N-containing substance having conjugated double bonds.
Key Words:
Coleus amboinicus Lour., cytotoxicity, antimicrobial, Arthrinium rasikravindrae, endophyte, fungus.
Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability
Merve BECİT*,° , Sevtap AYDIN DİLSİZ** , and Nurşen BAŞARAN***
* ORCİD: 0000-0002-8084-4419, Department of Pharmacology, Faculty of Pharmacy, Ataturk University, Erzurum, 25240, TURKEY
** ORCİD: 0000-0002-6368-2745, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, 06100, TURKEY
*** ORCİD: 0000-0001-8581-8933, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, 06100, TURKEY
° Corresponding Author: Merve BECİT
Phone: +904422315241; Fax: +904422315201; e-mail: mervebecit@hotmail.com
SUMMARY
Many challenges of hepatocellular carcinoma treatment, such as side effects and drug resistance, still remain. Therefore, new improvements with high pharmaceutical function and low toxicity
are needed. Recently, the efficacy of the combination therapy of antineoplastic drugs with natural products like pycnogenol has garnered attention. Pycnogenol® is a standardized extract from the bark of Pinus pinaster and consists of phenolic compounds. Pycnogenol is considered complementary in the treatments of some cancer besides its good tolerability and high safety. This study aims to reveal the synergistic effects of pycnogenol combination with cisplatin and its relation to human hepatocellular carcinoma (HepG2) cell viability. Effects of single and combined treatment on cell viability were evaluated in Chinese hamster lung fibroblasts (V79) and HepG2 cells using MTT assay. In HepG2 cells, this combined treatment showed a more cytotoxic effect than singledose
groups. Pycnogenol increased the cytotoxicity of cisplatin at 500 μM for 24 h; at 250-500 μM for 48 h in V79 cells; and also, at 125-500 μM for 24 h; at 62.5-500 μM for 48 h in HepG2 cells (p<0.05). Our study is the first study to show that pycnogenol treatment with cisplatin has been combined in the HepG2 cell line. As a result, pycnogenol induced cisplatin cytotoxicity via combined treatment on HepG2 cells and exhibited a synergistic effect with cisplatin. In conclusion, pycnogenol may play a role in the chemotherapy of hepatocellular carcinoma; however, further
studies are required to confirm their interactions with cisplatin.
Key Words:
Pycnogenol, cisplatin, MTT, cancer, hepatocellular carcinoma, HepG2 cells.
Improvement in Aqueous Solubility of Cilnidipine by Amorphous Solid Dispersion, Its Formulation into Interpenetrating Polymer Network Microparticles and Optimization by Box-Behnken Design
Amit KUHIKAR* , Shagufta KHAN**° , Komal KHARABE*** ,
Dilesh SINGHAVI**** , Girish DAHIKAR*****
* ORCID: 0000-0001-7353-9814, Institute of Pharmaceutical Education and Research, Borgaon (Meghe) Wardha, Maharashtra, India.
** ORCID:0000-0002-2827-7939, Institute of Pharmaceutical Education and Research, Borgaon (Meghe) Wardha, Maharashtra, India.
*** ORCID: 0000-0002-5237-6929, Institute of Pharmaceutical Education and Research, Borgaon (Meghe) Wardha, Maharashtra, India.
**** ORCID: 0000-0002-2544-7226, Institute of Pharmaceutical Education and Research, Borgaon (Meghe) Wardha, Maharashtra, India.
***** ORCID: 0000-0002-2284-535X, Institute of Pharmaceutical Education and Research, Borgaon (Meghe) Wardha, Maharashtra, India.
°Corresponding Author: Shagufta Khan, Professor,
Phone: (+91)7152-240284, Fax (+91)7152-241684; e-mail: shaguftakhan17@rediffmail.com
SUMMARY
Cilnidipine(CPN), a Biopharmaceutics Classification System class II drug, has dissolution rate-limited bioavailability and a very short half-life (20.4 min). Thus, there is a need to improve the solubility and prolong the drug release so that the therapeutic concentration of CPN could be maintained for a prolonged time. Therefore, the present investigation was aimed to improve the solubility of CPN by preparing amorphous solid dispersion (ASD) and sustain its release by incorporating CPN loaded ASD (CPNASD) in interpenetrating polymer network (IPN) microparticles. ASD was prepared using Solutol HS 15 and Gelucire®50/13. Solutol HS 15 provided a better effect by increasing 84.09 folds solubility of CPNASD in water as compared to the free CPN, therefore it was used in the formulation of IPN microparticles. Characterization of ASD by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed a decrease in the crystallinity
of CPN. IPN microparticles loaded with CPNASD were prepared by varying chitosan concentrations, polyvinyl alcohol (PVA), and massratio of chitosan:TPP and optimized by Box-Behnken Design. The constraints on the responses were maximum drug entrapment efficiency and sustained drug release with more than 80% drug release in 12 h. IPN microparticles with composition, chitosan 50mg, PVA 74.99mg (Volume of aqueous phase; 10 ml, Volume of organic phase; 50 ml) and chitosan:TPP 2.52 was the predicted optimized condition by the software and IPN with this composition provided high % entrapment efficiency (83.87±0.85) and sustained release (83.29±0.55) for 12 h. Solutol HS 15 was successful in providing a massive increase in solubility of CPN, and a uniform sustained release was achieved by loading CPNASD in IPN microparticles.
Key Words:
Cilnidipine, Solid dispersion, Solutol HS 15, Interpenetrating polymer network microparticles, Chitosan, Polyvinyl alcohol.
Turkish