TITLE

Differential binding of plasma proteins by liposomes loaded with lipophilic prodrugs of methotrexate and melphalan in the bilayer

AUTHOR(S)
Kuznetsova, N.; Vodovozova, E.
PUB. DATE
August 2014
SOURCE
Biochemistry (00062979);Aug2014, Vol. 79 Issue 8, p797
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Immediately upon contact with blood, nanosized drug delivery systems become coated with a so-called protein corona. The quantitative and qualitative composition of the corona defines not only the behavior of the nanocarrier in the circulation but, ultimately, the pharmacokinetics and biodistribution of the encapsulated drug as well. In turn, the composition of the protein corona depends on the surface properties of the nanoparticles, such as size and distribution of charge and functional groups on the particle surface. Liposomes belong to the most bio- and hemocompatible drug delivery systems feasible for intravenous route of administration required in chemotherapy of metastasizing tumors. However, knowledge on the interactions of liposomes of various compositions with blood plasma proteins remains fragmentary. Moreover, all nanosized drug delivery systems are potential targets for the innate immunity system, primarily the complement (C) system, which underlies frequent cases of hypersensitivity reactions. Recently, in a panel of in vitro hemocompatibility tests, we demonstrated that liposomes built of natural phospholipids - egg phosphatidylcholine and phosphatidylinositol from Saccharomyces cerevisiae - and loaded with diglyceride conjugates of anticancer drugs melphalan and methotrexate, did not affect the morphology and numbers of the main blood cell types. While preparations with melphalan prodrug were also inert in coagulation and C activation tests, methotrexate-loaded liposomes caused impaired coagulation and C activation. The aim of this work was to study the interactions of liposomes carrying prodrugs of melphalan and methotrexate with blood plasma proteins in vitro. Data on protein binding capacity of liposomes obtained with classical gel permeation chromatography techniques allowed for prediction of rather rapid elimination of the liposomes from circulation. A number of differences revealed through immunoblotting of the liposome-bound proteins agree with the previously obtained data on C activation. The possible mechanism of C activation by methotrexate-containing liposomes is discussed.
ACCESSION #
97444678

 

Related Articles

  • ADME Related Profiling in 96 and 384 Well Plate Format - A Novel and Robust HT-Assay for the Determination of Lipophilicity and Serum Albumin Binding. Hartmann, Thorsten; Schmitt, Johannes; Röhring, Cornelia; Nimptsch, Daniel; Nöller, Joachim; Mohr, Christoph // Current Drug Delivery;Jun2006, Vol. 3 Issue 2, p181 

    The failure of about half of the drug candidates is associated with poor pharmacokinetic properties leading to a huge loss of time and money [1]. Early profiling of drug like properties provides important information in order to screen out insoluble, poorly absorbed and toxic compounds. Today,...

  • Prodrugs -- An Efficient Way to Breach Delivery and Targeting Barriers. Huttunen, Kristiina M.; Rautio, Jarkko // Current Topics in Medicinal Chemistry;Sep2011, Vol. 11 Issue 18, p2265 

    The study of prodrugs that are chemically modified bioreversible derivatives of active drug compounds to alter their undesired properties has been expanded widely during the last decades. Despite the commercial success the prodrugs have afforded, the concept is still quite unknown among many...

  • Synthesis and In Vitro Skin Permeation of Naproxen Conjugates with a- Alkylamino Acids. Pignatello, Rosario; Montenegro, Lucia; Stancampiano, Annalisa H. S.; Puelo, Antonina; Puglisi, Giovanni // Current Drug Delivery;Jun2005, Vol. 2 Issue 2, p185 

    Novel amide conjugates of the NSAID naproxen (NAP, 1) with short-chain a-alkylamino acids (C4 to C6 alkyl chain) were synthesized through a carbodiimide (EDAC)-assisted coupling reaction and evaluated as dermal prodrugs of NAP. The 2-a-aminobutyl derivative (2) showed lipophilicity similar to...

  • Design of Prodrugs to Enhance Colonic Absorption by Increasing Lipophilicity and Blocking Ionization. Nofsinger, Rebecca; Clas, Sophie-Dorothee; Sanchez, Rosa I.; Walji, Abbas; Manser, Kimberly; Nissley, Becky; Balsells, Jaume; Nair, Amrithraj; Qun Dang; Bennett, David Jonathan; Hafey, Michael; Junying Wang; Higgins, John; Templeton, Allen; Coleman, Paul; Grobler, Jay; Smith, Ronald; Yunhui Wu // Pharmaceuticals;Feb2014, Vol. 7 Issue 2, p207 

    Prodrugs are chemistry-enabled drug delivery modifications of active molecules designed to enhance their pharmacokinetic, pharmacodynamic and/or biopharmaceutical properties. Ideally, prodrugs are efficiently converted in vivo, through chemical or enzymatic transformations, to the active parent...

  • Product Development Studies of Amino Acid Conjugate of Aceclofenac. Singh, Ajay Pal; Ramadan, Wafa Mossa; Dahiya, Rajiv; Sarpal, A. S.; Pathak, Kamla // Current Drug Delivery;Apr2009, Vol. 6 Issue 2, p208 

    The prodrugs designed by classical approach increase lipophilicity of the drug, which decreases the water solubility thus decreasing the concentration gradient, which controls drug absorption. To overcome the limitations of traditional prodrug approach, water soluble prodrugs can be designed by...

  • Investigation of Solvolysis Kinetics of New Synthesized Fluocinolone Acetonide C-21 Esters—An In Vitro Model for Prodrug Activation. Markovic, Bojan D.; Dobricic, Vladimir D.; Vladimirov, Sote M.; Cudina, Olivera A.; Savic, Vladimir M.; Karljikovic-Rajic, Katarina D. // Molecules;Mar2011, Vol. 16 Issue 3, p2658 

    In this study the solvolysis of newly synthesized fluocinolone acetonide C-21 esters was analysed in comparison with fluocinonide during a 24-hour period of time. The solvolysis was performed in an ethanol-water (90:10 v/v) mixture using the excess of NaHCO3. The solvolytic mixtures of each...

  • Synthesis of 1-adamantyloxyalkanols. Reznikov, A. N.; Skomorokhov, M. Yu.; Klimochkin, Yu. N. // Russian Journal of Organic Chemistry;Nov2010, Vol. 46 Issue 11, p1741 

    The article discusses the study which determines the synthesis of biologically active adamantane derivatives that may be used as drugs against viral diseases. It features the high antiviral activity of lipophilic modifiers for designing prodrugs of high biologic accessibility. It implies that...

  • Synthesis, Physicochemical Properties and In Vitro Permeation Studies of New Ketorolac Ester Derivatives. Puglia, Carmelo; Filosa, Rosanna; Peduto, Antonella; De Caprariis, Paolo; Boatto, Gianpiero; Nieddu, Maria; Santagati, Natale Alfredo; Bonina, Francesco // Current Drug Delivery;Sep2007, Vol. 4 Issue 3, p205 

    Six new 1-alkylazacycloalkan-2-one esters of ketorolac (1-6) were synthesized and evaluated as potential dermal prodrugs. In vitro experiments were carried out to evaluate their chemical and enzymatic stability and permeation through excised human skin. Furthermore, partition coefficients...

  • Corneal absorption and anterior chamber pharmacokinetics of dipeptide monoester prodrugs of ganciclovir (GCV): in vivo comparative evaluation of these prodrugs with Val-GCV and GCV in rabbits. Gunda, Sriram; Hariharan, Sudharshan; Mitra, Ashim K. // Journal of Ocular Pharmacology & Therapeutics;Dec2006, Vol. 22 Issue 6, p465 

    Aim: The overall aim of this study was to evaluate the corneal absorption of dipeptide monoester prodrugs of ganciclovir (GCV) and compare these results with L-valine-GCV and GCV. Another aim was to evaluate the pharmacokinetics of these prodrugs in aqueous humor.Methods:...

Share

Read the Article

Courtesy of NEW JERSEY STATE LIBRARY

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics