한빛사논문
- 조회780
Hytham H. Gadallaa,b, Seongsoo Leec, Hyungjun Kima,d, Abigail T. Armstronga, Dina Fathallab, Fawzia Habibb, Hyunyoung Jeonga,e, Wooin Leec, Yoon Yeoa,f
aDepartment of Industrial and Physical Pharmacy, Purdue University, 575 West Stadium Avenue, West Lafayette, IN 47907, USA
bDepartment of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
cCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
dDepartment of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi, Gyeongbuk 39177, Republic of Korea
eDepartment of Pharmacy Practice, Purdue University, West Lafayette, IN 47907, USA
fWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
Corresponding authors: Wooin Lee, Yoon Yeo
Abstract
Carfilzomib (CFZ) is a second-generation proteasome inhibitor effective in blood cancer therapy. However, CFZ has shown limited efficacy in solid tumor therapy due to the short half-life and poor tumor distribution. Albumin-coated nanocrystal (NC) formulation was shown to improve the circulation stability of CFZ, but its antitumor efficacy remained suboptimal. We hypothesize that NC size reduction is critical to the formulation safety and efficacy as the small size would decrease the distribution in the reticuloendothelial system (RES) and selectively increase the uptake by tumor cells. We controlled the size of CFZ-NCs by varying the production parameters in the crystallization-in-medium method and compared the size-reduced CFZ-NCs (z-average of 168 nm, NC168) with a larger counterpart (z-average of 325 nm, NC325) as well as the commercial CFZ formulation (CFZ-CD). Both CFZ-NCs showed similar or higher cytotoxicity than CFZ-CD against breast cancer cells. NC168 showed greater uptake by cancer cells, less uptake by macrophages and lower immune cell toxicity than NC325 or CFZ-CD. NC168, but not NC325, showed a similar safety profile to CFZ-CD in vivo. The biodistribution and antitumor efficacy of CFZ-NCs in mice were also size-dependent. NC168 showed greater antitumor efficacy and tumor accumulation but lower RES accumulation than NC325 in 4T1 breast cancer model. These results support that NC formulation with an optimal particle size can improve the therapeutic efficacy of CFZ in solid tumors.
논문정보
- Research article
- 2022년 12월 (BRIC 등록일 2023-01-16)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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