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: A549 cell lines; Erlotinib; biodistribution; glutathione nanosponge; human lung cancer; pyromellitic anhydride.