A Comparative In Vivo Study of Albumin‐Coated Paclitaxel Nanocrystals and Abraxane |
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| Authors: | Joonyoung Park Ji Eun Park Victoria E. Hedrick Karl V. Wood Connie Bonham Wooin Lee Yoon Yeo |
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| Affiliation: | 1. Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, USA;2. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea;3. Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA;4. Department of Chemistry, Purdue University, West Lafayette, IN, USA;5. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA |
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| Abstract: | Nanoparticulate drug carriers exploit the enhanced permeability of tumor vasculature to achieve selective delivery of chemotherapeutic drugs. For this purpose, nanoparticles (NPs) need to circulate with a long half‐life, enter tumors via the permeable vasculature and stay in tumors via favorable interactions with tumor cells. To fulfill these requirements, albumin‐coated nanocrystal formulation of paclitaxel (PTX), Cim‐F‐alb, featuring high drug loading content, physical stability in serum, and surface‐bound albumin in its native conformation is prepared. The pharmacokinetic and biodistribution (PK/BD) profiles of Cim‐F‐alb in a mouse model of B16F10 melanoma show that Cim‐F‐alb exhibits a longer plasma half‐life and a greater PTX deposition in tumors than Abraxane by ≈1.5 and ≈4.6 fold, respectively. Biolayer interferometry analysis indicates that Cim‐F‐alb has less interaction with serum proteins than nanocrystals lacking albumin coating, indicating the protective effect of the surface‐bound albumin against opsonization in the initial deposition phase. With the advantageous PK/BD profiles, Cim‐F‐alb shows greater and longer‐lasting anticancer efficacy than Abraxane at the equivalent dose. This study demonstrates the significance of controlling circulation stability and surface property of NPs in efficient drug delivery to tumors and enhanced anticancer efficacy. |
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| Keywords: | Abraxane albumin nanocrystals paclitaxel pharmacokinetics |
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