Hyaluronic acid decorated lipid nanocarrier for MDR modulation and CD-44 targeting in colon adenocarcinoma

Int J Biol Macromol. 2015 Jan:72:569-74. doi: 10.1016/j.ijbiomac.2014.09.005. Epub 2014 Sep 16.

Abstract

In present investigation, we developed a novel hyaluronated cationic nanostructured lipid carrier (CNLCs) which contains CPT-11/irinotecan to target CD44 biomarker which commonly overexpresses on colon cancer. The cationic core NLCs was developed by using capmule MCM and compritol as mix lipid phase with 150 ± 2.5 nm particles size and 93.98 ± 2.5% entrapment efficiency. The cationic core NLCs were coated with hyaluronic acid by ionic conjugation. The particle size of hyaluronated CNLCs was enhanced to 255 ± 4.2 nm. In-vitro drug release studies revealed a slow and sustain release of the drug and a practically no leaching of coumarin-6. The confocal laser microscopy studies were performed with developed CNLCs in two CD44 overexpressing cell lines (HT-29 and Colo-320). The studies revealed marked uptake of the CNLCs by both the cell lines in just two hours. The results were comparable to the FITC conjugated CD44 antibodies. Therefore, the developed dual purpose CNLCs were found to be highly specific for CD44 biomarker. The developed formulations were found to be compatible with blood components. The MTT assay revealed that the developed particles had enhanced cytotoxicity against non-MDR as well MDR cancer cells.

Keywords: CD44; Hyaluronic acid; MDR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Camptothecin / chemistry
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Coumarins / administration & dosage
  • Coumarins / chemistry
  • Drug Delivery Systems*
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • HT29 Cells
  • Humans
  • Hyaluronan Receptors / drug effects
  • Hyaluronic Acid / administration & dosage*
  • Hyaluronic Acid / chemistry
  • Irinotecan
  • Lipids / administration & dosage
  • Lipids / chemistry
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Thiazoles / administration & dosage
  • Thiazoles / chemistry

Substances

  • Coumarins
  • Hyaluronan Receptors
  • Lipids
  • Thiazoles
  • coumarin 6
  • Irinotecan
  • Hyaluronic Acid
  • Camptothecin