lumefantrine and Lung-Neoplasms

Conventional treatment options for lung cancer treatment were restricted due to non-specific nature and side effects, with this associated problem and to overcome this we had developed lumefantrine with nano calcium phosphate loaded lipid nanoparticles (LF- CaP- Ls) affording pH sensitive mechanism. Herein, the present study the in vivo anti-cancer property of LF-CaP-Ls was checked in mice models. Further, reduced lung cancer progression of lumefantrine with nano calcium phosphate loaded lipid nanoparticles (LF-CaP-Ls) treated mice were assessed by measuring the 5-methyltetrahydrofolate (MTHF) in serum. Moreover, LF-CaP-Ls showed substantially a anticancer effect compared to that of lumefantrine loaded lipid nanoparticles (LF-Ls) and free lumefantrine (LF) by exhibiting higher effects in lung tumor bearing mice model as confirmed by reduced tumor progression. Histopathological examination of lungs supported with H&E staining proved the reduced tumor vasculature and reduced inflammatory cells for LF-CaP-Ls compared to that of free LF and LF-Ls. Further, visual inspection with acetic acid test confirmed the reduced tumor progression for LF-CaP-Ls compared to that of free LF and LF-Ls. Altogether, the overall results suggested that the developed LF-CaP-Ls may acts as a better therapeutic molecule for lung cancer due to its maintenance of increased level of 5-MTHF levels, reduced tumor weight. Further, hematological and biochemical parameters were measured and supports our in-vivo therapeutic effect of LF-CaP-Ls.

Topics: Animals; Calcium Phosphates; Hydrogen-Ion Concentration; Lipids; Lumefantrine; Lung Neoplasms; Mice; Nanoparticles

The present work aim to develop pH responsive nanosystem comprising lumefantrine with calcium phosphate nanoparticles loaded lipidic cubosomes for the effective treatment of lung cancer. FTIR results showed that, compatibility nature of selected excipients for the synthesis of LF-CaP-Cs. The XRD results showed developed LF-CaP-Cs were non crystalline in nature. The selected developed LF-CaP-Cs were in cubic phase with average particle size of 259.4 ± 19 nm with a charge of -2.28 ± 0.7 mV. 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 (84.04 ± 0.4%) compared to pH 7.4 (48.32 ± 1.6%) 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 (28 ± 1.8 μg/mL) was significantly higher than that of free LF (40 ± 0.9 μg/mL). The results of cellular uptake study proved the localization of LF at cellular level and AO/EB staining results revealed that the A549 cell undergoes apoptosis in A549 cells.

Topics: A549 Cells; Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Calcium Phosphates; Cell Membrane Permeability; Cell Survival; Drug Compounding; Drug Liberation; Excipients; Humans; Hydrogen-Ion Concentration; Lipids; Lumefantrine; Lung Neoplasms; Molecular Targeted Therapy; Nanocapsules; Rats, Inbred WF