From Lipid Formulations to Inorganic and Hybrid Nanoparticles

Total Page:16

File Type:pdf, Size:1020Kb

From Lipid Formulations to Inorganic and Hybrid Nanoparticles International Journal of Molecular Sciences Review Nanocarriers for Biomedicine: From Lipid Formulations to Inorganic and Hybrid Nanoparticles Ruslan Kashapov *, Alsu Ibragimova, Rais Pavlov, Dinar Gabdrakhmanov, Nadezda Kashapova, Evgenia Burilova, Lucia Zakharova and Oleg Sinyashin A.E. Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Street 8, 420088 Kazan, Russia; [email protected] (A.I.); [email protected] (R.P.); [email protected] (D.G.); [email protected] (N.K.); [email protected] (E.B.); [email protected] (L.Z.); [email protected] (O.S.) * Correspondence: [email protected]; Tel.: +7-(843)-273-22-93; Fax: +7-(843)-273-22-53 Abstract: Encapsulation of cargoes in nanocontainers is widely used in different fields to solve the problems of their solubility, homogeneity, stability, protection from unwanted chemical and biological destructive effects, and functional activity improvement. This approach is of special importance in biomedicine, since this makes it possible to reduce the limitations of drug delivery related to the toxicity and side effects of therapeutics, their low bioavailability and biocompatibility. This review highlights current progress in the use of lipid systems to deliver active substances to the human body. Various lipid compositions modified with amphiphilic open-chain and macrocyclic compounds, peptide molecules and alternative target ligands are discussed. Liposome modification also evolves by creating new hybrid structures consisting of organic and inorganic parts. Such nanohybrid platforms include cerasomes, which are considered as alternative nanocarriers allowing to reduce inherent limitations of lipid nanoparticles. Compositions based on mesoporous silica Citation: Kashapov,R.; Ibragimova, A.; are beginning to acquire no less relevance due to their unique features, such as advanced porous Pavlov, R.; Gabdrakhmanov, D.; Kashapova, N.; Burilova, E.; properties, well-proven drug delivery efficiency and their versatility for creating highly efficient Zakharova, L.; Sinyashin, O. nanomaterials. The types of silica nanoparticles, their efficacy in biomedical applications and hybrid Nanocarriers for Biomedicine: From inorganic-polymer platforms are the subject of discussion in this review, with current challenges Lipid Formulations to Inorganic and emphasized. Hybrid Nanoparticles. Int. J. Mol. Sci. 2021, 22, 7055. https://doi.org/ Keywords: drug delivery; liposome; non-covalent modification; surfactant; peptide; macrocycle; 10.3390/ijms22137055 mesoporous silica; hybrid nanocarriers; cerasome Academic Editor: Christian Celia Received: 3 June 2021 1. Introduction Accepted: 26 June 2021 Published: 30 June 2021 One of the ways to improve the effectiveness of medical therapies is the use of drug delivery systems. This makes it possible to increase bioavailability and biocompatibility of Publisher’s Note: MDPI stays neutral drugs, to optimize their release profile, overcome biological barriers, and control targeting with regard to jurisdictional claims in properties, cellular uptake and intracellular trafficking [1–3]. Of particular interest is the published maps and institutional affil- delivery of anticancer drugs that can, in the future, reduce the severity of disease and iations. mortality rate. The chemotherapy drugs used today for the treatment of tumors, such as 5-fluorouracil, methotrexate and doxorubicin (DOX), do efficiently suppress tumors, but also cause concomitant tissue damage, which leads to the development of adverse reactions comparable in severity to the underlying disease. In this concern, the nanosystems capable of shielding a chemotherapy drug from interacting with healthy tissues and their release Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. after penetrating into tumor cells, are of great interest. Despite numerous publications This article is an open access article on the topic, this problem has not yet been fully resolved, and further progress in this distributed under the terms and area is obviously related to a rational design of nanocarriers with controlled transport conditions of the Creative Commons properties, morphology and size, taking into account the behavior in biological media and Attribution (CC BY) license (https:// mechanisms of penetration into cells. creativecommons.org/licenses/by/ To construct drug carriers, numerous strategies are developed, in which different 4.0/). factors should be taken into account, including size characteristics, composition of formu- Int. J. Mol. Sci. 2021, 22, 7055. https://doi.org/10.3390/ijms22137055 https://www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2021, 22, 7055 2 of 50 lations, nature and therapeutic indications of the drug, and a route of administration. A powerful tool for engineering the formulated medicines is their conjugation with functional ligands, thereby producing prodrugs with beneficial characteristics. For this purpose, polyethylene glycol (PEG), peptides and amphiphilic molecules are used [4–8], which allow modifying pharmacokinetics, toxicity, targeting properties, stimuli responsibility and other effects. Alternatively, encapsulation techniques are used, which provide effective facilities for the design of drug delivery systems. Importantly, the combination of these approaches may be successfully applied, resulting in synergic effect. Encapsulation strate- gies address different techniques and involve numerous types of systems composed of a variety of materials, which can be basically divided in organic and inorganic carriers. In turn, the two main families of organic systems are those based on amphiphilic (lipid and surfactant) [9–11] and polymeric [12,13] compounds. Both these groups provide marked advances in efficacy of loaded drugs due to optimizing their circulation and stability in bioenvironment. Essential feature of organic formulations is soft nature of the systems that allow for tailoring of morphology and shape characteristics, thereby providing the diversity of forms and sub-types of nanocarriers, including liposomes, solid lipid nanoparticles, nanostructural lipid particles, nanoemulsions, cubosomes, polymersomes, etc. [14,15]. In- organic nanoparticles, e.g., metal oxides, gold and silica particles, fullerenes, quantum dots, etc., provide effective and versatile platform for the fabrication of drug delivery vehicles and diagnostic imaging agents [16–18]. These materials demonstrate exclusive optical, mag- netic and electric properties in combination with enhanced loading capacity, mechanical stability, easy fabrication, controlled size and/or pore characteristics and other beneficial features, which can be tailored through proper choice of synthetic and functionalization techniques. Meanwhile, the highest biomedicine potential in terms of efficacy of therapy, safety, targeted delivery, triggered release, reduced toxicity and side effect can be offered by hybrid nanocarriers [19–22]. The current trends towards the development of hybrid for- mulations allow for attaining the synergy of beneficial properties of organic/inorganic [18], polymer/inorganic [19], lipid/inorganic [20], lipid/polymer [21] systems, etc. The urgency of this review is motivated by an intensively developed sphere of drug delivery, which is reflected in sharp growth of publications on this theme. High interest of researchers in the design of different types of nanocontainers occurs, with a clear trend towards multifunctional and complicated formulations observed. Meanwhile, there are a number of recent comprehensive reviews in different specific aspects, in which drug delivery systems are classified based on the chemical nature and prescription of a medicine, the type of nanocarriers [9], the target site [3,23,24] and the administration route [25,26]. Alternatively, based on the above analysis, two distinct families of nanocarriers, namely, lipid formulations and silicon-containing nanoparticles (Figure1), as well as intermediary cerasomes, have been chosen herein, with a focus on recent publications covering the drug encapsulation technique and emphasizing the aspects insufficiently highlighted elsewhere, e.g., development of hybrid formulations via non-covalent modification of nanocarriers aimed at the improving of their stability, targeting effects, multicentered drug loading and toxicity profile. First, liposomal formulations are discussed, with main attention paid to those non-covalently modified with surfactants, peptide moieties, macrocycles and other ligands that may offer targeting properties, morphological diversity, additional binding sites for drugs, etc. Further, mesoporous silica nanoparticles are reviewed, with those modified by polymers emphasized. Various liposomal forms containing inorganic frag- ments, namely lipid-modified mesoporous nanoparticles and cerasomes are also considered. Such structure of the review may allow researchers to receive comparative analysis of these nanocarriers and their potential applications for different drugs and administration pathways. Int. J. Mol. Sci. 2021, 22, x FOR PEER REVIEW 3 of 52 Int. J. Mol. Sci. 2021, 22, 7055 3 of 50 Figure 1. Main types of lipid- and silicon-containing nanoparticles, comprising many kinds of Figure 1. Mainnanocarriers types of lipid that- canand be silicon used-containing to achieve thenanoparticles, best medical comprising performance. many kinds of nanocarriers that can be used to achieve the best medical performance. 2. Lipid Formulations: Modification with Surfactants, Peptides, and Macrocycles
Recommended publications
  • NIH Public Access Author Manuscript CA Cancer J Clin
    NIH Public Access Author Manuscript CA Cancer J Clin. Author manuscript; available in PMC 2012 July 1. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: CA Cancer J Clin. 2011 ; 61(4): 250±281. doi:10.3322/caac.20114. PHOTODYNAMIC THERAPY OF CANCER: AN UPDATE Patrizia Agostinis1, Kristian Berg2, Keith A. Cengel3, Thomas H. Foster4, Albert W. Girotti5, Sandra O. Gollnick6, Stephen M. Hahn3, Michael R. Hamblin7,8,9, Asta Juzeniene2, David Kessel10, Mladen Korbelik11, Johan Moan2,12, Pawel Mroz7,8, Dominika Nowis13, Jacques Piette14, Brian C. Wilson15, and Jakub Golab13,16,* 1Department of Molecular Cell Biology, Cell Death Research & Therapy Laboratory, Catholic University of Leuven, B-3000 Leuven, Belgium, [email protected] 2Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway, [email protected]; [email protected] 3Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19004, USA, [email protected]; [email protected] 4Department of Imaging Sciences, University of Rochester, Rochester, NY 14642, USA, [email protected] 5Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, 53226-3548, USA, [email protected] 6Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA, [email protected] 7Wellman Center for Photomedicine,
    [Show full text]
  • Modifications to the Harmonized Tariff Schedule of the United States To
    U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b).
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • Section B Changed Classes/Guidelines Final
    EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2019 Section B Changed Classes/Guidelines Final Version Date of issue: 24th December 2018 1 A3 FUNCTIONAL GASTRO-INTESTINAL DISORDER DRUGS R2003 A3A PLAIN ANTISPASMODICS AND ANTICHOLINERGICS R1993 Includes all plain synthetic and natural antispasmodics and anticholinergics. A3B Out of use; can be reused. A3C ANTISPASMODIC/ATARACTIC COMBINATIONS This group includes combinations with tranquillisers, meprobamate and/or barbiturates except when they are indicated for disorders of the autonomic nervous system and neurasthenia, in which case they are classified in N5B4. A3D ANTISPASMODIC/ANALGESIC COMBINATIONS R1997 This group includes combinations with analgesics. Products also containing either tranquillisers or barbiturates and analgesics to be also classified in this group. Antispasmodics indicated exclusively for dysmenorrhoea are classified in G2X1. A3E ANTISPASMODICS COMBINED WITH OTHER PRODUCTS r2011 Includes all other combinations not specified in A3C, A3D and A3F. Combinations of antispasmodics and antacids are classified in A2A3; antispasmodics with antiulcerants are classified in A2B9. Combinations of antispasmodics with antiflatulents are classified here. A3F GASTROPROKINETICS r2013 This group includes products used for dyspepsia and gastro-oesophageal reflux. Compounds included are: alizapride, bromopride, cisapride, clebopride, cinitapride, domperidone, levosulpiride, metoclopramide, trimebutine. Prucalopride is classified in A6A9. Combinations of gastroprokinetics with other substances
    [Show full text]
  • A Novel 5-Fluorouracil-Resistant Human Esophageal Squamous Cell Carcinoma Cell Line Eca-109/5-FU with Significant Drug Resistance-Related Characteristics
    2942 ONCOLOGY REPORTS 37: 2942-2954, 2017 A novel 5-fluorouracil-resistant human esophageal squamous cell carcinoma cell line Eca-109/5-FU with significant drug resistance-related characteristics CHI ZHANG1*, QUNFENG MA2*, YINAN SHI1, XUE LI1, MING WANG1, JUNFENG WANG1, JIANLIN GE1, ZHINAN CHEN3, ZILING WANG1 and HONG JIANG1 1College of Life Science and Bioengineering, School of Science, Beijing Jiaotong University, Haidian, Beijing 100044; 2Department of Thoracic Surgery, Affiliated Hospital of the Academy of Military Medical Sciences, Fengtai, Beijing 100071; 3Cell Engineering Research Center, The Fourth Military Medical University, Xicheng, Xi'an, Shaanxi 710032, P.R. China Received September 1, 2016; Accepted October 31, 2016 DOI: 10.3892/or.2017.5539 Abstract. 5-Fluorouracil (5-FU) is used for the clinical treat- metabolite profile, such as lactate, glutamate, taurine, gluta- ment of esophageal squamous cell carcinomas (ESCCs), yet mine, proline, aspartate, methanol, cystine, glycine and uracil. it also induces chemoresistant cancer cells during treatment, Our results identified that the resistant cell line Eca-109/5-FU which leads to the failure of the therapy. To further explore showed quite different characteristics compared with the the resistance mechanism of 5-FU in ESCC, we established parental Eca-109 cells. The Eca-109/5-FU cell line provides the 5-FU-resistant ESCC cell line Eca-109/5-FU, which was an experimental model for further steps to select chemothera- prepared by the stepwise exposure to increasing 5-FU concen- peutic sensitizers. trations. MTT assay and nude mouse xenograft models were used to test the drug resistance and proliferation of Eca-109 Introduction and Eca-109/5-FU cells in vitro and in vivo.
    [Show full text]
  • I Regulations
    23.2.2007 EN Official Journal of the European Union L 56/1 I (Acts adopted under the EC Treaty/Euratom Treaty whose publication is obligatory) REGULATIONS COUNCIL REGULATION (EC) No 129/2007 of 12 February 2007 providing for duty-free treatment for specified pharmaceutical active ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation and specified products used for the manufacture of finished pharmaceuticals and amending Annex I to Regulation (EEC) No 2658/87 THE COUNCIL OF THE EUROPEAN UNION, (4) In the course of three such reviews it was concluded that a certain number of additional INNs and intermediates used for production and manufacture of finished pharmaceu- ticals should be granted duty-free treatment, that certain of Having regard to the Treaty establishing the European Commu- these intermediates should be transferred to the list of INNs, nity, and in particular Article 133 thereof, and that the list of specified prefixes and suffixes for salts, esters or hydrates of INNs should be expanded. Having regard to the proposal from the Commission, (5) Council Regulation (EEC) No 2658/87 of 23 July 1987 on the tariff and statistical nomenclature and on the Common Customs Tariff (1) established the Combined Nomenclature Whereas: (CN) and set out the conventional duty rates of the Common Customs Tariff. (1) In the course of the Uruguay Round negotiations, the Community and a number of countries agreed that duty- (6) Regulation (EEC) No 2658/87 should therefore be amended free treatment should be granted to pharmaceutical accordingly, products falling within the Harmonised System (HS) Chapter 30 and HS headings 2936, 2937, 2939 and 2941 as well as to designated pharmaceutical active HAS ADOPTED THIS REGULATION: ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation, specified salts, esters or hydrates of such INNs, and designated inter- Article 1 mediates used for the production and manufacture of finished products.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0226431 A1 Habib (43) Pub
    US 20090226431A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0226431 A1 Habib (43) Pub. Date: Sep. 10, 2009 (54) TREATMENT OF CANCER AND OTHER Publication Classification DISEASES (51) Int. Cl. A 6LX 3/575 (2006.01) (76)76) InventorInventor: Nabilabil Habib,Habib. Beirut (LB(LB) C07J 9/00 (2006.01) Correspondence Address: A 6LX 39/395 (2006.01) 101 FEDERAL STREET A6IP 29/00 (2006.01) A6IP35/00 (2006.01) (21) Appl. No.: 12/085,892 A6IP37/00 (2006.01) 1-1. (52) U.S. Cl. ...................... 424/133.1:552/551; 514/182: (22) PCT Filed: Nov.30, 2006 514/171 (86). PCT No.: PCT/US2O06/045665 (57) ABSTRACT .."St. Mar. 6, 2009 The present invention relates to a novel compound (e.g., 24-ethyl-cholestane-3B.5C,6C.-triol), its production, its use, and to methods of treating neoplasms and other tumors as Related U.S. Application Data well as other diseases including hypercholesterolemia, (60) Provisional application No. 60/741,725, filed on Dec. autoimmune diseases, viral diseases (e.g., hepatitis B, hepa 2, 2005. titis C, or HIV), and diabetes. F2: . - 2 . : F2z "..., . Cz: ".. .. 2. , tie - . 2 2. , "Sphagoshgelin , , re Cls Phosphatidiglethanolamine * - 2 .- . t - r y ... CBs .. A . - . Patent Application Publication Sep. 10, 2009 Sheet 1 of 16 US 2009/0226431 A1 E. e'' . Phosphatidylcholine. " . Ez'.. C.2 . Phosphatidylserias. * . - A. z' C. w E. a...2 .". is 2 - - " - B 2. Sphingoshgelin . Cls Phosphatidglethanglamine Figure 1 Patent Application Publication Sep. 10, 2009 Sheet 2 of 16 US 2009/0226431 A1 Chile Phosphater Glycerol Phosphatidylcholine E.
    [Show full text]
  • Photodynamic Therapy Using Talaporfin Sodium for Local Failure
    Journal of Clinical Medicine Article Photodynamic Therapy Using Talaporfin Sodium for Local Failure after Chemoradiotherapy or Radiotherapy for Esophageal Cancer: A Single Center Experience Natsuki Ishida 1 , Satoshi Osawa 2,* , Takahiro Miyazu 1, Masanao Kaneko 1, Satoshi Tamura 1, Shinya Tani 2, Mihoko Yamade 1, Moriya Iwaizumi 3, Yasushi Hamaya 1, Takahisa Furuta 4 and Ken Sugimoto 1 1 First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan; [email protected] (N.I.); [email protected] (T.M.); [email protected] (M.K.); [email protected] (S.T.); [email protected] (M.Y.); [email protected] (Y.H.); [email protected] (K.S.) 2 Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan; [email protected] 3 Department of Laboratory Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan; [email protected] 4 Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-53-435-2261 Received: 21 April 2020; Accepted: 13 May 2020; Published: 17 May 2020 Abstract: A phase II study of second-generation photodynamic therapy (PDT) using talaporfin sodium has shown excellent treatment results for esophageal cancer with local failure after chemoradiotherapy (CRT) or radiotherapy (RT). However, only a few studies have reported this therapy in clinical practice.
    [Show full text]
  • WO 2012/136553 Al 11 October 2012 (11.10.2012) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2012/136553 Al 11 October 2012 (11.10.2012) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 487/04 (2006.01) A61P 35/00 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/519 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, PCT/EP2012/055600 HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, 29 March 2012 (29.03.2012) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (26) Publication Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 1116 1111.7 5 April 201 1 (05.04.201 1) EP kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (71) Applicant (for all designated States except US): Bayer UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, Pharma Aktiengesellschaft [DE/DE]; Muller Strasse 178, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, 13353 Berlin (DE).
    [Show full text]
  • Original Article Novel 5-Fluorouracil-Resistant Human Esophageal Squamous Cell Carcinoma Cells with Dihydropyrimidine Dehydrogenase Overexpression
    Am J Cancer Res 2015;5(8):2431-2440 www.ajcr.us /ISSN:2156-6976/ajcr0012352 Original Article Novel 5-fluorouracil-resistant human esophageal squamous cell carcinoma cells with dihydropyrimidine dehydrogenase overexpression Osamu Kikuchi1, Shinya Ohashi2, Yukie Nakai2, Shunsaku Nakagawa3, Kazuaki Matsuoka4, Takashi Kobunai4, Teiji Takechi4, Yusuke Amanuma2, Masahiro Yoshioka1, Tomomi Ida2,5, Yoshihiro Yamamoto5, Yasushi Okuno5, Shin’ichi Miyamoto1, Hiroshi Nakagawa6, Kazuo Matsubara3, Tsutomu Chiba1, Manabu Muto2 Departments of 1Gastroenterology and Hepatology, 2Therapeutic Oncology, 5Clinical Systems Onco-Informatics, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; 3Department of Pharmacy, Kyoto University Hospital, Kyoto 606-8507, Japan; 4Translational Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima 771-0194, Japan; 6Gastroenterology Division, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA Received July 3, 2015; Accepted July 8, 2015; Epub July 15, 2015; Published August 1, 2015 Abstract: 5-Fluorouracil (5-FU) is a key drug for the treatment of esophageal squamous cell carcinoma (ESCC); however, resistance to it remains a critical limitation to its clinical use. To clarify the mechanisms of 5-FU resistance of ESCC, we originally established 5-FU-resistant ESCC cells, TE-5R, by step-wise treatment with continuously in- creasing concentrations of 5-FU. The half maximal inhibitory concentration of 5-FU showed that TE-5R cells were 15.6-fold more resistant to 5-FU in comparison with parental TE-5 cells. TE-5R cells showed regional copy number amplification of chromosome 1p including theDPYD gene, as well as high mRNA and protein expressions of dihydro- pyrimidine dehydrogenase (DPD), an enzyme involved in 5-FU degradation.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity Against Human Oral Squamous Cell Carcinoma
    medicines Review Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma Yoshiaki Sugita 1,*, Koichi Takao 1, Yoshihiro Uesawa 2,* , Junko Nagai 2 , Yosuke Iijima 3, Motohiko Sano 4 and Hiroshi Sakagami 5,* 1 Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan; [email protected] 2 Department of Medical Molecular Informatics, Meiji Pharmaceutical University, Tokyo 204-858, Japan; [email protected] 3 Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, Japan; [email protected] 4 Division of Applied Pharmaceutical Education and Research, Hoshi University, Tokyo 142-8501, Japan; [email protected] 5 Meikai University Research Institute of Odontology (M-RIO), 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan * Correspondence: [email protected] (Y.S.); [email protected] (Y.U.); [email protected] (H.S.); Tel.: +81-492-717-254 (Y.S.); +81-424-958-983 (Y.U.); +81-492-792-758 (H.S.) Received: 3 August 2020; Accepted: 24 August 2020; Published: 26 August 2020 Abstract: Since many anticancer drugs show severe adverse effects such as mucositis, peripheral neurotoxicity, and extravasation, it was crucial to explore new compounds with much reduced adverse effects. Comprehensive investigation with human malignant and nonmalignant cells demonstrated that derivatives of chromone, back-bone structure of flavonoid, showed much higher tumor specificity as compared with three major polyphenols in the natural kingdom, such as lignin-carbohydrate complex, tannin, and flavonoid. A total 291 newly synthesized compounds of 17 groups (consisting of 12 chromones, 2 esters, and 3 amides) gave a wide range of the intensity of tumor specificity, possibly reflecting the fitness for the optimal 3D structure and electric state.
    [Show full text]