Preparation and Evaluation of Cabazitaxel-Loaded Bovine Serum Albumin Nanoparticles for Prostate Cancer
Authors Wan Z, Xie F, Wang L, Zhang G, Zhang H
Received 19 April 2020
Accepted for publication 15 July 2020
Published 29 July 2020 Volume 2020:15 Pages 5333—5344
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Linlin Sun
Zhong Wan1 ,* Fangyuan Xie2 ,* Liang Wang,3 Guoqing Zhang,2 Hai Zhang3
1Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People’s Republic of China; 2Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People’s Republic of China; 3Department of Pharmacy, Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai 201204, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Guoqing Zhang
Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People’s Republic of China
Tel/ Fax +86-21-81875571
Department of Pharmacy, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, People’s Republic of China
Tel/ Fax +86 21-20261401
Purpose: Cabazitaxel (CBZ) is a new taxane-based antitumor drug approved by the FDA for the treatment of prostate cancer, especially for patients with advanced prostate cancer for whom docetaxel is ineffective or causes aggravation. However, Tween 80 injection can cause serious allergic reactions, and CBZ itself has strong toxicity, adverse reactions, and poor tumor selectivity, which greatly limits its clinical applications. Therefore, the CBZ-loaded bovine serum albumin nanoparticles (CBZ-BSA-Gd-NPs) were developed to overcome the allergenic response of Tween 80 and realize the integration of diagnosis and treatment.
Methods: CBZ-BSA-Gd-NPs were prepared by the biomineralization method. The characterization, magnetic resonance imaging (MRI), safety, and antitumor activity of the nanoparticles were evaluated in vitro and in vivo.
Results: The prepared nanoparticles were uniform in size (166 nm), with good MRI performance and stability over 24 h. Compared with CBZ-Tween 80 injection, CBZ-BSA-Gd-NPs showed much lower hemolysis, similar tumor inhibition, and enhanced cellular uptake in vitro. The pharmacokinetic behavior of CBZ-BSA-Gd-NPs in rats showed that the retention time of the nanoparticles was prolonged, the clearance rate decreased, and the area under the drug-time curve increased. The distribution of CBZ-BSA-Gd-NPs in nude mice was characterized by UPLC-MS/MS and MRI, and the results showed that CBZ-BSA-Gd-NPs could effectively target tumor tissues with reduced distribution in the heart, liver, spleen, lungs, and kidneys compared with CBZ-Tween 80, which indicated that CBZ-BSA-Gd-NPs not only had a passive targeting effect on tumor tissue but also achieved the integration of diagnosis and treatment. In vivo, CBZ-BSA-Gd-NPs showed improved tumor inhibitory effect with a safer profile.
Conclusion: In summary, CBZ-BSA-Gd-NPs can serve as an effective therapeutic drug carrier to deliver CBZ into prostate cancer, and realize the integration of diagnosis and therapy.
Keywords: cabazitaxel, bovine serum albumin, nanoparticles, prostate cancer, magnetic resonance imaging, gadolinium
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