Development of ph responsive nanoparticulate drug delivery system for the effective treatment of lung cancer

Abstract

Lung cancer is characterized by uncontrolled growth of cells in tissue/cells in lungs. Thereby, the cancer cell spreads to nearby tissues or cells through metastasis. Lung cancer is the leading cause of cancer-associated mortality globally, with a low survival rate. The present work aim to develop pH responsive nanoparticulate system comprising lumefantrine with calcium phosphate nanoparticles loaded lipidic cubosomes (LF-CaP-Cs) for the effective treatment of lung cancer. Cubosomes (Cs) based nano system has been chosen for the present work due to its bi-continuous phase (both lipid and water), enhanced drug loading capacity, higher surface area, stable characteristics, viscous nature, bio-adhesivity and biocompatible. Lumefantrine is water insoluble antimalarial drug recently reported for its anti-cancer activity. Due to pH responsive behavior, calcium phosphate nanoparticles (CaP) gets dispersed at acidic pH (both endosomal/lysosomal pH) thereby the osmotic pressure inside the cellular compartments gets increased thereby leads to endosomal escape. Here, LF with calcium phosphate nanoparticle loaded cubosomes (LF-CaP-Cs) was developed and characterized. FTIR results showed that, compatibility nature of selected excipients for the synthesis of LF-CaP-Cs. The XRD results showed that LF-CaP-Cs were non-crystalline in nature. The selected developed LF-CaP-Cs was in cubic phase with average particle size in the range of 250 nm with a negative zeta potential. The encapsulation efficiency for LF within LF-CaP-Cs was about 78.76 ± 0.5%. RP-HPLC analysis showed that LF release rate gets significantly enhanced with higher peak area at pH 4.0 compared to pH 5.0/pH 7.4. The in-vitro release of LF-CaP-Cs showed that LF release gets significantly increased at pH 4.0 compared to pH 7.4 at 12 h. Further, CAM assay showed the superior anti-angiogenesis potential of developed LF-CaP-Cs compared to LF-Cs/blank Cs. The cytotoxicity effect of LF-CaP-Cs was significantly higher than that of free. newline