Augmented delivery of gemcitabine in lung cancer cells exploring mannose anchored solid lipid nanoparticles

J Colloid Interface Sci. 2016 Nov 1:481:107-16. doi: 10.1016/j.jcis.2016.07.020. Epub 2016 Jul 12.

Abstract

Gemcitabine (GmcH) is an effective anti-cancer agent used in the chemotherapy of lung cancer. However, the clinical applications of GmcH has been impeded primarily due to its low blood residence time, unfavorable pharmacokinetic and pharmacodynamic (PK/PD) profile, and poor penetration in the complex environment of lung cancer cells. Thus, the present study aims to formulate GmcH loaded mannosylated solid lipid nanoparticles (GmcH-SLNs) for improving its drug uptake into the lung cancer cells. GmcH-SLNs were prepared by emulsification and solvent evaporation process, and surface modification was done with mannose using ring opening technique. The cellular toxicity and cell uptake studies were performed in A549 lung adenocarcinoma cell line. The developed nanoformulation appears to be proficient in targeted delivery of GmcH with improved therapeutic effectiveness and enhanced safety.

Keywords: Drug delivery; Gemcitabine; Lung cancer; Solid lipid nanoparticles.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacokinetics*
  • Antimetabolites, Antineoplastic / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacokinetics
  • Deoxycytidine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems*
  • Gemcitabine
  • Humans
  • Lipids / chemistry*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mannose / chemistry*
  • Nanoparticles / chemistry*
  • Structure-Activity Relationship

Substances

  • Antimetabolites, Antineoplastic
  • Lipids
  • Deoxycytidine
  • Mannose
  • Gemcitabine