Lactobionic acid coupled liposomes: an innovative strategy for targeting hepatocellular carcinoma

Drug Deliv. 2016;23(1):140-6. doi: 10.3109/10717544.2014.907373. Epub 2014 Apr 30.

Abstract

Introduction: Liver cancer or hepatocellular carcinoma (HCC) is a major cause of death worldwide. Targeted delivery of drug to the carcinoma cell can be achieved by conjugation of ligand on the carrier system.

Methods and materials: In this study, oxaliplatin-loaded hepatoma-targeted liposome were designed and prepared using galactosylated distearoylphosphatidylethanolamine. The liposomes were prepared by cast film method and coupled with lactobionic acid (LA-LP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as a coupling agent. The coupling was confirmed by infrared spectroscopy. They were further characterized for various parameters such as vesicle shape and surface morphology, size, entrapment efficiency and in vitro release pattern.

Results and discussion: The vesicle size of the uncoupled liposome (256 nm) was found to be less than LA-LP (310 nm). The uptake of LA-LP and uncoupled liposomes by BEL7402 HCC cell lines was visualized using fluorescence microscopy that revealed the dependence of liposomal recognition and higher uptake of the LA-LP. Organ distribution studies provided evidence that coupling of lactobionic acid on liposomal surface significantly enhanced the tumor uptake of drug, which is reflected by recovery of higher percentage of drug from tumor as compared to uncoupled liposomes or free drug.

Conclusion: These studies suggest them as effective vectors for HCC targeting.

Keywords: Carcinoma; hepatocellular; lactobionic acid; liposomes; oxaliplatin.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Disaccharides / chemistry*
  • Drug Carriers / chemistry*
  • Drug Delivery Systems
  • Ethyldimethylaminopropyl Carbodiimide
  • Liposomes / chemistry
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Particle Size
  • Phosphatidylethanolamines
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Disaccharides
  • Drug Carriers
  • Liposomes
  • Organoplatinum Compounds
  • Phosphatidylethanolamines
  • Oxaliplatin
  • 1,2-distearoylphosphatidylethanolamine
  • lactobionic acid
  • Ethyldimethylaminopropyl Carbodiimide