The antitumor activity of PNA modified vinblastine cationic liposomes on Lewis lung tumor cells: In vitro and in vivo evaluation

• Published in: International journal of pharmaceutics Vol. 487; no. 1-2; pp. 223 - 233
• Main Authors: Li, Xue-tao, He, Mei-li, Zhou, Zhi-yan, Jiang, Ying, Cheng, Lan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.06.2015
• Subjects: Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis Regulatory Proteins - metabolism; Carcinoma, Lewis Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - drug therapy; Cationic liposomes; Cell Line, Tumor; Coumarins - chemistry; Drug Compounding; Liposomes; Mice; Mice, Inbred C57BL; Nanoparticles; Non-small cell lung cancer; Particle Size; Peanut agglutinin; Peanut Agglutinin - pharmacology; Vinblastine; Vinblastine - administration & dosage; Vinblastine - pharmacology; Xenograft Model Antitumor Assays; Peanut agglutinin; Cationic liposomes; Vinblastine; Non-small cell lung cancer
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2015.04.035

[Display omitted] Non-small cell lung cancer (NSCLC) is one of the frequently-occurring disease in the world, and the treatment effects are usually unsatisfactory. Vinblastine is an anti-microtubule drug in clinic. In this study, a nanostructured liposome was designed and prepared for treating NSCLC. In the liposomes, peanut agglutinin (PNA) was modified on the liposomal surface, 3-(N-(N′,N′-dimethylaminoethane)carbamoyl) cholesterol was used as cationic materials, and vinblastine was encapsulated in the aqueous core of liposomes, respectively. The PNA modified vinblastine cationic liposomes were approximately 100nm in size with a positive potential. In vitro results showed that the targeting liposomes could significantly enhance cellular uptake, selectively accumulate in LLT cells, and dramatically initiate apoptosis via activating pro-apoptotic proteins and apoptotic enzymes, thus leading to the strongest antitumor efficacy to LLT cells. In vivo results demonstrated that the targeting liposomes could display a prolonged circulation time in the blood, accumulate more drug in tumor location, and induce most of tumor cells apoptosis. As a result, a robust overall antitumor efficacy in tumor-bearing mice was observed subsequently. In conclusion, the chemotherapy using the PNA modified vinblastine cationic liposomes could provide a potential strategy for treating non-small cell lung cancer.