[The increase in receptor-mediated endocytosis of drugs in the composition of nanoparticles with the address fragment]

Biomed Khim. 2016 Mar;62(3):306-10. doi: 10.18097/PBMC20166203306.
[Article in Russian]

Abstract

It is known that disorders in the cell functioning of the organs/tissues is accompanied by increased expression of certain receptors. A modern approach to improve the specificity of the drug accumulation in the affected area is to construct the delivery nanosystems with the address fragments. Active tagged transport may help to reduce the dose of the drug, minimizing the impact on healthy cells and organs (reduced adverse events). This approach is particularly important in oncology because of the high toxicity of the drugs used. In this work we have obtained and characterized the pharmaceutical composition of doxorubicin and chlorine e6 into colloidal nanoparticles with synthesized previously targeted conjugates based on folic acid and biotin. On the cell culture Hep G2 it was shown an increase in the internalization of drugs when they were introduced in the incubation medium in the form of drug compositions with transport nanosystems and targeted fragments.

Izvestno, chto narushenie v funktsionirovanii kletok organov/tkaneĭ soprovozhdaetsia povyshennoĭ ékspressieĭ tekh ili inykh retseptorov. Sovremennym podkhodom dlia povysheniia spetsifichnosti nakopleniia lekarstvennykh soedineniĭ v oblasti porazheniia iavliaetsia konstruirovanie transportnykh sistem, snabzhennykh adresnym fragmentom. Napravlennyĭ transport pozvoliaet snizhat' dozu vvodimogo lekarstvennogo sredstva, za schet chego minimizirovat' ego vozdeĭstvie na zdorovye kletki (snizit' pobochnye proiavleniia). Takoĭ podkhod osobenno vazhen v onkologii iz-za vysokoĭ toksichnosti ispol'zuemykh preparatov. V nastoiashcheĭ rabote polucheny i okharakterizovany lekarstvennye kompozitsii doksorubitsina i khlorina e6 v sostave kolloidnykh nanochastits s sintezirovannymi ranee adresnymi fragmentami na osnove folievoĭ kisloty i biotina. V éksperimentakh na kul'ture kletok Hep G2 pokazano, chto vkliuchenie issleduemykh lekarstvennykh preparatov v fosfolipidnye nanochastitsy, snabzhennye adresnymi fragmentami, privodit k dostovernomu uvelicheniiu ikh internalizatsii.

Keywords: Hep G2; biotin; folic acid; intracellular internalization; targeted delivery system.

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / chemistry
  • Biotin / chemistry
  • Chlorophyllides
  • Doxorubicin / adverse effects*
  • Doxorubicin / chemistry
  • Endocytosis*
  • Folic Acid / chemistry
  • Hep G2 Cells
  • Humans
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism*
  • Porphyrins / chemistry

Substances

  • Antineoplastic Agents
  • Chlorophyllides
  • Porphyrins
  • phytochlorin
  • Biotin
  • Doxorubicin
  • Folic Acid