4.6 Article

Co-delivery of berberine and magnolol targeted liposomes for synergistic anti-lung cancer

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DOI: 10.1016/j.colsurfa.2023.131773

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Berberine; Magnolol; Combination therapy; Targeted liposomes; Lung cancer

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In this study, researchers developed chondroitin sulfate modified liposomes containing berberine and magnolol. These liposomes showed excellent targeting ability towards A549 lung cancer cells and demonstrated a sustained drug release profile. They effectively inhibited tumor growth and induced apoptosis in tumor cells.
Lung cancer is the leading cause of both new cancer cases and deaths. Both Berberine (BBR)and Magnolol (MAG) have specific anti-lung cancer effects. However, the adverse properties of direct administration of BBR and MAG largely limited the anti-cancer effects, such as short circulation time and poor selectivity. In this work, the optimal molar ratio of BBR to MAG (2:1) was chosen based on the synergistic anti-lung cancer effect. The chondroitin sulfate (CS) modified liposomes (CS-Lip-MB) were developed to co-deliver BBR and MAG by the film dispersion combined with the pH gradient method, which could specifically bind to the CD44 receptor highly expressed A549 cells, thus improving the tumor targeting and synergistic anti-cancer effect. The optimum composition of the formulation (weight ratio) hydrogenated soy phospholipid (HSPC): cholesterol: stearylamine: MAG:BBR was 18:5:0.69:1:1 with the CS concentration of 3 mg center dot mL (-1). CS-Lip-MB showed extended drug release performances, and improved the uptake by A549 cells, thus enhancing the toxicity and migration-blocking impact on tumor cells, and promoting cell apoptosis. The apoptosis mechanism is related to the regulation of the expressions of Bcl-2, Bax and Caspase-3. Meanwhile, the results of in vivo biodistribution and pharmacokinetics indicated that CS-Lip-MB could improve the blood stability, prolong the circulation time, and increase in vivo targeting of free drugs. CS-Lip-MB significantly inhibited tumor growth and reduced toxic side effects in A549-bearing nude mice with the highest tumor inhibition rate of 81.48%. In summary, CS-Lip-MB liposomes exhibited great potential for synergistic therapy of lung cancer with improved blood stability, excellent targeting ability and superior in vivo anti-lung cancer effect.

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