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Use of biotin targeted methotrexate–human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy

Authors Taheri A, Dinarvand R, Salman Nouri F, Khorramizadeh MR, Taheri Borougeni A, Mansoori P, Atyabi F

Published 8 September 2011 Volume 2011:6 Pages 1863—1874

DOI https://doi.org/10.2147/IJN.S23949

Review by Single-blind

Peer reviewer comments 4

Azade Taheri1, Rassoul Dinarvand1,2, Faranak Salman Nouri1, Mohammad Reza Khorramizadeh3, Atefeh Taheri Borougeni4, Pooria Mansoori5, Fatemeh Atyabi1,2
1Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical sciences, Tehran, Iran; 3Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Tehran University of Medical Sciences, Tehran, Iran; 5Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract: Biotin molecules could be used as suitable targeting moieties in targeted drug delivery systems against tumors. To develop a biotin targeted drug delivery system, we employed human serum albumin (HSA) as a carrier. Methotrexate (MTX) molecules were conjugated to HSA. MTX-HSA nanoparticles (MTX-HSA NPs) were prepared from these conjugates by cross-linking the HSA molecules. Biotin molecules were then conjugated on the surface of MTX-HSA NPs. The anticancer efficacy of biotin targeted MTX-HSA NPs was evaluated in mice bearing 4T1 breast carcinoma. A single dose of biotin targeted MTX-HSA NPs showed stronger in vivo antitumor activity than non-targeted MTX-HSA NPs and free MTX. By 7 days after treatment, average tumor volume in the biotin targeted MTX-HSA NPs-treated group decreased to 17.6% of the initial tumor volume when the number of attached biotin molecules on MTX-HSA-NPs was the highest. Average tumor volume in non-targeted MTX-HSA NPs-treated mice grew rapidly and reached 250.7% of the initial tumor volume. Biotin targeted MTX-HSA NPs increased the survival of tumor-bearing mice to 47.5 ± 0.71 days and increased their life span up to 216.7%. Mice treated with biotin targeted MTX-HSA NPs showed slight body weight loss (8%) 21 days after treatment, whereas non-targeted MTX-HSA NPs treatment at the same dose caused a body weight loss of 27.05% ± 3.1%.

Keywords: biotin, targeted drug delivery, in vivo anticancer delivery, human serum albumin, methotrexate, conjugates

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