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