PURPOSE: The study reports the initial biological evaluation of targeted polymeric glycol chitosan vesicles as carrier systems for doxorubicin (Dox). METHODS: Transferrin (Tf) was covalently bound to the Dox-loaded palmitoylated glycol chitosan (GCP) vesicles using dimethylsuberimidate (DMSI). For comparison, glucose targeted niosomes were prepared using N-palmitoyl glucosamine. Biological properties were studied using confocal microscopy, flow cytometry, and cytotoxicity assays as well as a mouse xenograft model. RESULTS: Tf vesicles were taken up rapidly with a plateau after 1-2 h and Dox reached the nucleus after 60-90 min. Uptake was not increased with the use of glucose ligands, but higher uptake and increased cytotoxicity were observed for Tf targeted as compared to GCP Dox alone. In the drug-resistant A2780AD cells and in A431 cells, the relative increase in activity was significantly higher for the Tf-GCP vesicles than would have been expected from the uptake studies. All vesicle formulations had a superior in vivo safety profile compared to the free drug. CONCLUSIONS: The in vitro advantage of targeted Tf vesicles did not translate into a therapeutic advantage in vivo. All vesicles reduced tumor size on day 2 but were overall less active than the free drug.
PURPOSE: The study reports the initial biological evaluation of targeted polymeric glycol chitosan vesicles as carrier systems for doxorubicin (Dox). METHODS:Transferrin (Tf) was covalently bound to the Dox-loaded palmitoylated glycol chitosan (GCP) vesicles using dimethylsuberimidate (DMSI). For comparison, glucose targeted niosomes were prepared using N-palmitoyl glucosamine. Biological properties were studied using confocal microscopy, flow cytometry, and cytotoxicity assays as well as a mouse xenograft model. RESULTS: Tf vesicles were taken up rapidly with a plateau after 1-2 h and Dox reached the nucleus after 60-90 min. Uptake was not increased with the use of glucose ligands, but higher uptake and increased cytotoxicity were observed for Tf targeted as compared to GCP Dox alone. In the drug-resistant A2780AD cells and in A431 cells, the relative increase in activity was significantly higher for the Tf-GCP vesicles than would have been expected from the uptake studies. All vesicle formulations had a superior in vivo safety profile compared to the free drug. CONCLUSIONS: The in vitro advantage of targeted Tf vesicles did not translate into a therapeutic advantage in vivo. All vesicles reduced tumor size on day 2 but were overall less active than the free drug.
Authors: H Hashizume; P Baluk; S Morikawa; J W McLean; G Thurston; S Roberge; R K Jain; D M McDonald Journal: Am J Pathol Date: 2000-04 Impact factor: 4.307
Authors: W L Monsky; D Fukumura; T Gohongi; M Ancukiewcz; H A Weich; V P Torchilin; F Yuan; R K Jain Journal: Cancer Res Date: 1999-08-15 Impact factor: 12.701
Authors: Nazila Kamaly; Zeyu Xiao; Pedro M Valencia; Aleksandar F Radovic-Moreno; Omid C Farokhzad Journal: Chem Soc Rev Date: 2012-03-05 Impact factor: 54.564
Authors: Sobia Noreen; Jin-Xiang Ma; Muhammad Saeed; Fahad Pervaiz; Muhammad Farhan Hanif; Bilal Ahmed; Muhammad Irshad Farooq; Faizan Akram; Muhammad Safdar; Asadullah Madni; Muhammad Naveed; Li Chang-Xing Journal: Drug Deliv Transl Res Date: 2022-04-30 Impact factor: 5.671