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Aclarubicin‐loaded cationic albumin‐conjugated pegylated nanoparticle for glioma chemotherapy in rats
Author(s) -
Lu Wei,
Wan Jin,
Zhang Qing,
She Zhenjue,
Jiang Xinguo
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22296
Subject(s) - aclarubicin , chemistry , glioma , microdialysis , albumin , pharmacology , doxorubicin , chemotherapy , cancer research , biochemistry , medicine , surgery , extracellular
Traditional glioma chemotherapy with those second‐line drugs such as anthracyclines usually failed because they are inaccessible to blood–brain barrier (BBB) in tumor. In our study, we incorporated aclarubicin (ACL) into cationic albumin‐conjugated pegylated nanoparticle (CBSA‐NP–ACL) to determine its therapeutic potential of rats with intracranially implanted C6 glioma cells. When labeled with fluorescent probe, 6‐coumarin, CBSA‐NP was shown to accumulate much more in tumor mass than nanoparticle without conjugated CBSA (NP) 1 hr post intravenous injection, as well as better retention after 24 hr. Tumor drug concentration of CBSA‐NP–ACL displayed 2.6‐ and 3.3‐fold higher than that of NP–ACL and ACL solution 1 hr post injection, while 2.7 and 6.6‐fold higher after 24 hr, respectively. Moreover, using tumor microdialysis sampling, AUC 0–24 hr of free drug amount in tumor interstitium delivered by CBSA‐NP–ACL was about 2.0‐ and 2.7‐fold higher than that of NP–ACL and ACL solutions, respectively. When the tumor rat model was subjected to 4 cycles of 2 mg/kg of ACL in different formulations, a significant increase of median survival time was found in the group of CBSA‐NP–ACL compared with that of saline control animals, animals treated with NP–ACL and ACL solution. By terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end‐labeling, CBSA‐NP–ACL can extensively make the tumor cell apoptosis. Histochemical evaluation by periodic acid Shiff staining and biochemical analysis depicted that the incorporation of ACL into CBSA‐NP reduced its toxicity to liver, kidney and heart. Besides, CBSA‐NP–ACL was not shown to open tight junction evaluated by BBB coculture. It was concluded that CBSA‐NP–ACL could have a therapeutic potential for treatment of glioma. © 2006 Wiley‐Liss, Inc.