In vitro and in vivo biological evaluation of O-carboxymethyl chitosan encapsulated metformin nanoparticles for pancreatic cancer therapy.

Abstract

PURPOSE:

In vitro anticancer effect and in vivo biodistribution and biocompatibility of metformin encapsulated O-Carboxymethyl chitosan nanoparticles were evaluated for its application as pancreatic cancer therapy.

METHODS:

In vitro studies such as cell migration assay, clonogenic assay, cell cycle analysis and qRT-PCR analysis were done in pancreatic cancer cells (MiaPaCa-2) treated with O-CMC-metformin NPs for evaluating its anticancer potential. In vivo biodistribution studies were carried out by NIR imaging of O-CMC-metformin NPs after tagging it with ICG. In vivo biocompatibility of the NPs was assessed by histopathology analysis of organs from mice administered with the NPs.

RESULTS:

In vitro cell migration assay showed marginal effect of NPs on migration property of pancreatic cancer cells (MiaPaCa-2). In vitro clonogenic assay established that the O-CMC-metformin NPs reduced colony formation ability of the cancer cells. While cell cycle analysis showed that the O-CMC-metformin NPs had only minor effect on progression of cell cycle in the cancer cells. qRT-PCR analysis exhibited reduced mRNA expression of p21, vanin 1 and MMP9 in pancreatic cancer cells treated with the nanoparticles. In vivo NIR imaging study showed normal biodistribution pattern of the intravenously injected O-CMC-metformin NPs suggesting normal clearance rate of nanoparticles and no adverse toxicity to the organs.

CONCLUSIONS:

The biocompatible O-CMC-metformin NPs with anticancer potential and capability for normal biodistribution can be beneficial for the treatment of pancreatic cancer.

• Authors: K S Snima, R Jayakumar, Vinoth-Kumar Lakshmanan
• Journal: Pharmaceutical research (Pharm Res) Vol. 31 Issue 12 Pg. 3361-70 (Dec 2014) ISSN: 1573-904X [Electronic] United States
• PMID: 25115827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Hypoglycemic Agents
• O-carboxymethylchitosan
• RNA, Messenger
• Chitosan
• Metformin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Movement
• Chitosan (analogs & derivatives, chemistry)
• Colony-Forming Units Assay
• Drug Compounding
• Humans
• Hypoglycemic Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Materials Testing
• Metformin (administration & dosage, pharmacokinetics, therapeutic use)
• Mice
• Pancreatic Neoplasms (drug therapy)
• RNA, Messenger (biosynthesis)
• Tissue Distribution