Improving Paclitaxel Delivery: In Vitro and In Vivo Characterization of

Jan 28, 2015 - Nanomedicine in management of hepatocellular carcinoma: Challenges and opportunities. Nourhan K. Mohamed , Mostafa A. Hamad ...
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Improving Paclitaxel Delivery: In Vitro and In Vivo Characterization of PEGylated Polyphosphoester-Based Nanocarriers Fuwu Zhang,† Shiyi Zhang,† Stephanie F. Pollack,†,‡ Richen Li,† Amelia M. Gonzalez,† Jingwei Fan,† Jiong Zou,† Sarah E. Leininger,† Adriana Pavía-Sanders,† Rachel Johnson,§ Laura D. Nelson,⊥ Jeffery E. Raymond,†,‡ Mahmoud Elsabahy,†,‡,∥ Dennis M. P. Hughes,⊥ Mark W. Lenox,§ Tiffany P. Gustafson,*,†,‡ and Karen L. Wooley*,†,‡ †

Departments of Chemistry, Chemical Engineering, and Materials Science and Engineering, ‡Laboratory for Synthetic-Biologic Interactions, and §Texas A&M Institute for Preclinical Studies, Texas A&M University, College Station, Texas 77842, United States ∥ Department of Pharmaceutics, and Assiut International Center of Nanomedicine, Al-Rajhy Liver Hospital, Assiut University, 71515 Assiut, Egypt ⊥ Department of Pediatric Research, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States S Supporting Information *

ABSTRACT: Nanomaterials have great potential to offer effective treatment against devastating diseases by providing sustained release of high concentrations of therapeutic agents locally, especially when the route of administration allows for direct access to the diseased tissues. Biodegradable polyphosphoester-based polymeric micelles and shell cross-linked knedel-like nanoparticles (SCKs) have been designed from amphiphilic block-graft terpolymers, PEBP-b-PBYP-g-PEG, which effectively incorporate high concentrations of paclitaxel (PTX). Well-dispersed nanoparticles physically loaded with PTX were prepared, exhibiting desirable physiochemical characteristics. Encapsulation of 10 wt% PTX, into either micelles or SCKs, allowed for aqueous suspension of PTX at concentrations up to 4.8 mg/mL, as compared to