Extended release delivery of erlotinib glutathione nanosponge for targeting lung cancer

Abstract

Systemic and uncontrolled administration of erlotinib hydrochloride (ETB) is associated with severe toxicity. A novel targeted and extended release nanosponge (NS) was synthesized from glutathione (GHS) by a one-step reaction between β-cyclodextrin and pyromellitic dianhydride at room temperature for delivery of ETB in lung cancer. Characterization studies were performed using sophisticated instruments. In-vitro release study was performed in the presence of incremental concentrations of GHS which was analyzed using HPLC. Cell cytotoxicity study was evaluated on human lung cancer (A549) cell lines. In-vivo tumour inhibition and biodistribution of ETB-loaded GHS-NS (ETB-NS) were performed on BALB/c mice. NS obtained was spherical, size 212 ± 2.45 nm and high drug entrapment (92.34 ± 5.31%) (p < .001). In-vitro extended drug release (76.89 ± 0.1% release at 168 h), which was directly proportional to the concentration of GHS, demonstrated tumour targeting. There was enhanced in-vitro cytotoxicity and 97.5% inhibition in tumour growth on administering NS when compared to plain ETB (48% inhibition) indicating targeting of NS to the tumour site. Biodistribution study and in-vivo tumour growth inhibition study revealed drug release to the cancerous cell, thus preventing unnecessary drug exposure. ETB-NS exhibits extended drug release proportional to the external GSH concentration.

Keywords:

• Erlotinib
• biodistribution
• glutathione nanosponge
• pyromellitic anhydride
• human lung cancer
• A549 cell lines

Acknowledgements

The authors are thankful to Cipla Pvt. Ltd. (Mumbai, India) for providing gift samples of erlotinib hydrochloride. Authors are thankful to Ms. Fatima Rafiq Zakaria, Chairman of Maulana Azad Educational Trust, Aurangabad (India) for providing the necessary infrastructure facilities. Special thanks to Dr. Ayaz Ali, Associate Professor, Y.B Chavan College of Pharmacy, Aurangabad (India) for his assistance in performing pharmacokinetic and biodistribution studies.

Disclosure statement

Authors declare no conflict of interest. All authors have contributed in the research.