Current Advances of Tubulin Inhibitors in Nanoparticle Drug Delivery and Vascular Disruption/Angiogenesis.
Extensive research over the last decade has resulted in a number of highly potent tubulin polymerization inhibitors acting either as microtubule stabilizing agents (MSAs) or microtubule destabilizing agents (MDAs). These inhibitors have potent cytotoxicity against a broad spectrum of human tumor cell lines. In addition to cytotoxicity, a number of these tubulin inhibitors have exhibited abilities to inhibit formation of new blood vessels as well as disrupt existing blood vessels. Tubulin inhibitors as a vascular disrupting agents (VDAs), mainly from the MDA family, induce rapid tumor vessel occlusion and massive tumor necrosis. Thus, tubulin inhibitors have become increasingly popular in the field of tumor vasculature. However, their pharmaceutical application is halted by a number of limitations including poor solubility and toxicity. Thus, recently, there has been considerable interests in the nanoparticle drug delivery of tubulin inhibitors to circumvent those limitations. This article reviews recent advances in nanoparticle based drug delivery for tubulin inhibitors as well as their tumor vasculature disruption properties.
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave. Memphis, TN 38163, USA. sbanerj5@uthsc.edu.
Souvik
S
Banerjee
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave. Memphis, TN 38163, USA. dhwang@uthsc.edu.
Dong-Jin
DJ
Hwang
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave. Memphis, TN 38163, USA. wli@uthsc.edu.
Wei
W
Li
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave. Memphis, TN 38163, USA. dmiller@uthsc.edu.
Duane D
DD
Miller
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001665:Binding Sites; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011485:Protein Binding; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000008:administration & dosage* / Q000737:chemistry
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004337:Drug Carriers; D014404:Tubulin; D050257:Tubulin Modulators
angiogenesis; antimitotic; multidrug resistance; nanoparticle formulations; tubulin dynamics; tubulin inhibitors; vascular disrupting agent; β-tubulin isotypes and drug resistance