Biotin receptor-targeting nanogels loaded with methotrexate for enhanced antitumor efficacy in triple-negative breast cancer in vitro and in vivo models.

Autor: Sadat Abolmaali S; Pharmaceutical Nanotechnology Department and Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz 71345, Iran. Electronic address: s.abolmaali@gmail.com., Zarenejad S; Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz 71345, Iran., Mohebi Y; Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz 71345, Iran., Najafi H; Pharmaceutical Nanotechnology Department and Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz 71345, Iran., Javanmardi S; Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz 71345, Iran., Abedi M; Pharmaceutical Nanotechnology Department and Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz 71345, Iran., Mohammad Tamaddon A; Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz 71345, Iran.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2022 Aug 25; Vol. 624, pp. 122049. Date of Electronic Publication: 2022 Jul 22.
DOI: 10.1016/j.ijpharm.2022.122049
Abstrakt: High-dose methotrexate (MTX) chemotherapeutic applications confront drug specificity and pharmacokinetic challenges, which can be overcome by utilizing targeted drug delivery systems. In the present study, biotin-PEG conjugated nanogels of carboxymethyl polyethyleneimine (Biotin-PEG-CMPEI) were developed for active targeted delivery of MTX in triple negative breast cancer (TNBC). TEM and DLS analyses revealed uniform, discrete, and spherical particles with a mean hydrodynamic diameter of about 100 nm and ζ-potential of + 15 mV (pH = 7.4). Biotin-PEG-CMPEI nanogels exhibited a zero-order MTX release kinetics at pH = 7.5 and a swelling-controlled release at pH = 5.5. In 4 T1 cells treated with the MTX-loaded Biotin-PEG-CMPEI, the IC 50 was reduced by about 10 folds compared to the free drug, while the unloaded nanogels showed no significant toxicity. In the model mice, the group treated with the MTX-loaded Biotin-PEG-CMPEI had a lower tumor volume and mortality rate animal model when compared to free drug. Additionally, histopathological analyses showed that the group treated with the MTX-loaded nanogels had less lung metastasis and glomerular damage caused by MTX. Overall, the MTX-loaded Biotin-PEG-CMPEI targeted directly against overexpressed biotin receptors in TNBC have been shown to improve the MTX safety and therapeutic efficacy.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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