Crizotinib-loaded polymeric nanoparticles in lung cancer chemotherapy.

Abstract

The study describes the development of polylactide-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS)-based nanosystem as a carrier of crizotinib (CZT) to achieve superior anticancer efficacy in lung cancer therapy. We have demonstrated that block copolymer and hydrophobic drug is capable of self-assembling into a very stable nanocarrier, with suitable properties that allow their application for cancer drug delivery. Drug release study showed a sustained release pattern as a result of entrapment in the hydrophobic core of micelles. CZT/PT NP showed a noticeable cytotoxic effect in NCIH3122 lung cancer cells in a dose-dependent manner. Furthermore, morphological imaging and Live/Dead assay revealed a superior anticancer efficacy for nanoformulations. The polymeric nanoparticle showed a predominant presence in the cytoplasmic region of cell, indicating a typical endocytosis-mediated cellular uptake. The annexin V/PI staining-based apoptosis assay showed a remarkable ~40 % apoptosis (early and late apoptosis cells) comparing to only ~25 % apoptosis by free CZT. Taken together, Vitamin E TPGS-modified PLA nanoparticles would be a potential drug delivery system to increase the chemotherapeutic efficacy of CZT in lung cancer chemotherapy.

• Authors: Zhi-Ming Jiang, Shou-Ping Dai, Yong-Qing Xu, Tao Li, Jian Xie, Chong Li, Zhong-Hui Zhang
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 32 Issue 7 Pg. 193 (Jul 2015) ISSN: 1559-131X [Electronic] United States
• PMID: 26025486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Polymers
• Pyrazoles
• Pyridines
• Succinates
• poly(lactide)-tocopheryl polyethylene glycol succinate
• Polyethylene Glycols
• Crizotinib

Topics

• Antineoplastic Agents (administration & dosage)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Crizotinib
• Drug Carriers (administration & dosage)
• Drug Delivery Systems (methods)
• Humans
• Lung Neoplasms (drug therapy)
• Nanoparticles (administration & dosage)
• Polyethylene Glycols (administration & dosage)
• Polymers (administration & dosage)
• Pyrazoles (administration & dosage)
• Pyridines (administration & dosage)
• Succinates (administration & dosage)