Jacob M. Berlin,†,¶ Ashley D. Leonard,†,¶ Tam T. Pham,†,¶ Daisuke Sano,§,¶ Daniela C. Marcano,† Shayou Yan,⬜ Stefania Fiorentino,⬜ Zvonimir L. Milas,§ Dmitry V. Kosynkin,† B. Katherine Price,† Rebecca M. Lucente-Schultz,† XiaoXia Wen,储 M. Gabriela Raso,⬜ Suzanne L. Craig,# Hai T. Tran,⬜ Jeffrey N. Myers,§,* and James M. Tour†,‡,*
ARTICLE
Effective Drug Delivery, In Vitro and In Vivo, by Carbon-Based Nanovectors Noncovalently Loaded with Unmodified Paclitaxel †
Department of Chemistry, and the ‡Smalley Institute for Nanoscale Science and Technology, Rice University, MS-222, 6100 Main Street, Houston, Texas 77005, §Head and Neck Surgery, Unit 441, ⬜Thoracic/Head and Neck Medical Oncology, 储Experimental Diagnostic Imaging, and #Department of Veterinary Medicine and Surgery, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030. ¶These authors contributed equally to this work.
n increasing number of drug candidates with high therapeutic efficacy have low water solubility, posing a challenge for in vivo delivery.1 We are seeking to develop a safe, modular drug delivery platform that can be loaded with unmodified hydrophobic drugs and thereby enable their delivery. Ideally, in the future, it will be possible to continue to develop this modular platform into a targeted drug delivery vehicle. In this paper, we describe the initial step toward this goal by demonstration of a nontargeted platform that can sequester and deliver a hydrophobic drug. Paclitaxel (PTX) is a classic example of a water-insoluble drug with high therapeutic efficacy. In the FDA-approved commercial formulation of PTX (Taxol, Bristol-MyersSquibb, Princeton, NJ), the drug is solubilized in ethanol and a polyethoxylated castor oil, Cremophor EL (Cremophor). The use of Cremophor as the excipient for PTX is well-known to cause significant allergic reactions, including anaphylaxis. Consequently, patients are premedicated with antihistamines and corticosteroids in order to prevent potentially life-threatening hypersensitivity reactions.2 One solution to this problem has been the sequestering of PTX in albumin, and the commercial formulation is called Abraxane.3 Though milder, significant side effects remain, such as sensory neuropathy.3 It is noteworthy that both commercial formulations of PTX involve the noncovalent sequestration of the unmodified drug, likely due to both the ease
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ABSTRACT Many new drugs have low aqueous solubility and high therapeutic efficacy. Paclitaxel (PTX) is a
classic example of this type of compound. Here we show that extremely small (
