McNeeley, Kathleen M. and Annapragada, Ananth and Bellamkonda, Ravi V. (2007) Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma. NANOTECHNOLOGY, 18 (38).
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Official URL: http://www.iop.org/EJ/abstract/0957-4484/18/38/385...
Liposomal and other nanocarrier based drug delivery vehicles can localize to tumours through passive and/ or active targeting. Passively targeted liposomal nanocarriers accumulate in tumours via ` leaky' vasculature through the enhanced permeability and retention ( EPR) effect. Passive accumulation depends upon the circulation time and the degree of tumour vessel ` leakiness'. After extravasation, actively targeted liposomal nanocarriers efficiently deliver their payload by receptor-mediated uptake. However, incorporation of targeting moieties can compromise circulation time in the blood due to recognition and clearance by the reticuloendothelial system, decreasing passive accumulation. Here, we compare the efficacy of passively targeted doxorubicin-loaded PEGylated liposomal nanocarriers to that of actively targeted liposomal nanocarriers in a rat 9L brain tumour model. Although folate receptor ( FR)-targeted liposomal nanocarriers had significantly reduced blood circulation time compared to PEGylated liposomal nanocarriers; intratumoural drug concentrations both at 20 and 50 h after administration were equal for both treatments. Both treatments significantly increased tumour inoculated animal survival by 60-80% compared to non-treated controls, but no difference in survival was observed between FR-targeted and passively targeted nanocarriers. Therefore, alternate approaches allowing for active targeting without compromising circulation time may be important for fully realizing the benefits of receptor-mediated active targeting of gliomas.
|Uncontrolled Keywords:||STERICALLY STABILIZED LIPOSOMES; TUMOR-BEARING MICE; CELLS IN-VITRO; DRUG-DELIVERY; STEALTH LIPOSOMES; ANTI-HER2 IMMUNOLIPOSOMES; POLY(ETHYLENE GLYCOL); CONJUGATED LIPOSOMES; THERAPEUTIC EFFICACY; ANTITUMOR-ACTIVITY|
|Subjects:||Biomedical Science > Nanobiotechnology|
|Deposited On:||23 Sep 2009 11:45|
|Last Modified:||23 Sep 2009 11:45|
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