Targeting of Micelles and Liposomes Loaded with the Pro-Apoptotic Drug, NCL-240, into NCI/ADR-RES Cells in a 3D Spheroid Model

• Published in: Pharmaceutical research Vol. 33; no. 10; pp. 2540 - 2551
• Main Authors: Pattni, Bhushan S., Nagelli, Srikar G., Aryasomayajula, Bhawani, Deshpande, Pranali P., Kulkarni, Abhijit, Hartner, William C., Thakur, Ganesh, Degterev, Alexei, Torchilin, Vladimir P.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2016; Springer; Springer Nature B.V
• Subjects: Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cancer; Cell Line, Tumor; Chlorophenols - administration & dosage; Chlorophenols - metabolism; Comparative analysis; Drug Delivery Systems - methods; Drug therapy; Female; Humans; Liposomes; Medical Law; Micelles; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Pharmacology/Toxicology; Pharmacy; Prodrugs - administration & dosage; Prodrugs - metabolism; Research Paper; Transferrin - administration & dosage; Transferrin - metabolism; Triazoles - administration & dosage; Triazoles - metabolism; Tumor Cells, Cultured; transferrin-targeted drug delivery; cancer spheroids; micelles; liposomes; NCL-240
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-016-1978-1

ABSTRACT Purpose To develop transferrin (Tf)-targeted delivery systems for the pro-apoptotic drug, NCL-240, and to evaluate the efficacy of this delivery system in ovarian cancer NCI/ADR-RES cells, grown in vitro in a 3D spheroid model. Methods Tf-targeted PEG-PE-based micellar and ePC/CHOL-based liposomal delivery systems for NCL-240 were prepared. NCI/ADR-RES cells were used to generate spheroids by a non-adhesive liquid overlay technique. Spheroid growth and development were monitored by size (diameter) analysis and H&E staining. The targeted formulations were compared to untargeted ones in terms of their degree of spheroid association and penetration. A cell viability analysis with NCL-240-loaded micelles and liposomes was performed to assess the effectiveness of Tf-targeting. Results Tf-targeted polymeric micelles and Tf-targeted liposomes loaded with NCL-240 were prepared. NCI/ADR-RES cells generated spheroids that demonstrated the presence of a distinct necrotic core along with proliferating cells in the spheroid periphery, partly mimicking in vivo tumors. The Tf-targeted micelles and liposomes had a deeper spheroid penetration as compared to the untargeted delivery systems. Cell viability studies using the spheroid model demonstrated that Tf-mediated targeting markedly improved the cytotoxicity profile of NCL-240. Conclusion Transferrin targeting enhanced delivery and effectiveness of micelles and liposomes loaded with NCL-240 against NCI/ADR-RES cancer cells in a 3D spheroid model.