PEG-Bottlebrush Stabilizer-Based Worm-like Nanocrystal Micelles with Long-Circulating and Controlled Release for Delivery of a BCR-ABL Inhibitor against Chronic Myeloid Leukemia (CML)

doi:10.3390/pharmaceutics14081662

	PEG-Bottlebrush Stabilizer-Based Worm-like Nanocrystal Micelles with Long-Circulating and Controlled Release for Delivery of a BCR-ABL Inhibitor against Chronic Myeloid Leukemia (CML)
	Liang, Huamin 2,3; Zou, Fengming 2,3; Fu, Liyi 2,3; Liu, Qingwang 2,3; Wang, Beilei 2,3; Liang, Xiaofei 2,3; Liu, Jing 1,2,3; Liu, Qingsong 1,2,3
刊名	PHARMACEUTICS
	2022-08-01
卷号	14
关键词	drug nanocrystal stabilizer micelle BCR-ABL chronic myeloid leukemia (CML)
DOI	10.3390/pharmaceutics14081662
通讯作者	Liu, Jing(jingliu@hmfl.ac.cn) ; Liu, Qingsong(qsliu97@hmfl.ac.cn)
英文摘要	Drug nanocrystals, one of most common drug delivery systems, enable the delivery of poorly water-soluble drugs with high drug loading and enhanced dissolution. The rapid clearance and uncontrolled drug release of drug nanocrystals limit their delivery efficiency and clinical application. Herein, an amphiphilic co-polymer, poly oligo(ethylene glycol) methacrylate-b-poly(styrene-co-4-formylphenyl methacrylate) (POEGMA-b-P (St-co-FPMA), PPP), characterized by a hydrophilic part with bottlebrush-like oligo(ethylene glycol) methacrylate (OEGMA) side chains, was synthesized as stabilizers to fabricate a high-drug-loading nanocrystal micelle (053-PPP NC micelle) using the chronic myeloid leukemia (CML) drug candidate N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053 or 053) as a model drug. The 053-PPP NC micelle was characterized and subjected to in vitro and in vivo studies. It featured a worm-like shape of small size, high drug loading (similar to 50%), high colloidal stability, and controlled release in vitro. The presence of the 053-PPP NC micelle resulted in a long-circulation property and a much higher AUC. The 053-PPP NC micelle induced higher accumulation in the tumor tissues under multiple continuous administration. For in vivo efficacy, the 053-PPP NC micelle with a longer dosing interval (96 h), beneficial for improving patient adherence, demonstrated superiority to the 053-F127 NC. The proposed stabilizer PPP and the 053-PPP NC micelle with high drug loading enables drug delivery with long circulation and controlled release of drugs. It is also promising for the development of more efficient nanocrystal-based intravenous injection formulations for poorly water-soluble drugs. It might also offer new possibilities for potential clinical application of the CML candidate drug 053.
资助项目	National Natural Science Foundation of China[82103976] ; National Natural Science Foundation of China[82173671] ; Anhui Provincial Natural Science Foundation[2108085J42] ; Anhui Provincial Natural Science Foundation[2108085QH377] ; Frontier Science Key Research Program of CAS[QYZDB-SSW-SLH037] ; CASHIPS Director's Fund[YZJJ2021QN38] ; Leading Talent Program of Hefei[2018-1-006] ; Youth Innovation Promotion Association of CAS[Y202088]
WOS关键词	DRUG ; NANOPARTICLE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	MDPI
WOS记录号	WOS:000847210600001
资助机构	National Natural Science Foundation of China ; Anhui Provincial Natural Science Foundation ; Frontier Science Key Research Program of CAS ; CASHIPS Director's Fund ; Leading Talent Program of Hefei ; Youth Innovation Promotion Association of CAS
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/131900]
专题	中国科学院合肥物质科学研究院
通讯作者	Liu, Jing; Liu, Qingsong
作者单位	1.Precis Med Res Lab Anhui Prov, Hefei 230088, Peoples R China 2.Chinese Acad Sci, Hefei Canc Hosp, Hefei 230031, Peoples R China 3.Chinese Acad Sci, Hefei Inst Phys Sci, Inst Hlth & Med Technol, Anhui Prov Key Lab Med Phys & Technol, Hefei 230031, Peoples R China
推荐引用方式 GB/T 7714	Liang, Huamin,Zou, Fengming,Fu, Liyi,et al. PEG-Bottlebrush Stabilizer-Based Worm-like Nanocrystal Micelles with Long-Circulating and Controlled Release for Delivery of a BCR-ABL Inhibitor against Chronic Myeloid Leukemia (CML)[J]. PHARMACEUTICS,2022,14.
APA	Liang, Huamin.,Zou, Fengming.,Fu, Liyi.,Liu, Qingwang.,Wang, Beilei.,...&Liu, Qingsong.(2022).PEG-Bottlebrush Stabilizer-Based Worm-like Nanocrystal Micelles with Long-Circulating and Controlled Release for Delivery of a BCR-ABL Inhibitor against Chronic Myeloid Leukemia (CML).PHARMACEUTICS,14.
MLA	Liang, Huamin,et al."PEG-Bottlebrush Stabilizer-Based Worm-like Nanocrystal Micelles with Long-Circulating and Controlled Release for Delivery of a BCR-ABL Inhibitor against Chronic Myeloid Leukemia (CML)".PHARMACEUTICS 14(2022).