Copyright © 2014 American Scientific Publishers All rights reserved Printed in the United States of America Review Journal of Biomedical Nanotechnology Vol. 10, 1–31, 2014 www.aspbs.com/jbn Nanopharmaceutics: Phytochemical-Based Controlled or Sustained Drug-Delivery Systems for Cancer Treatment Roubeena Jeetah, Archana Bhaw-Luximon, and Dhanjay Jhurry ∗ ANDI Centre of Excellence for Biomedical and Biomaterials Research, MSIRI Building, University of Mauritius, Réduit, Mauritius This review is an attempt to assess the different classes of phytochemicals and some of their members which have been encapsulated into nanocarrier systems for their chemotherapeutic or chemopreventive properties. Given the broad spec- trum of nanomedicines currently in clinical trial and clinical use from polymer-protein conjugates, through nanocrystals, nanogels, dendrimers to ethosomes, the focus of this review will be on block copolymer nanomicelles, nanoparticles, polymer-drug conjugates, liposomes and solid lipid nanocarriers (SLNs). The twenty phytochemicals investigated for encapsulation and targeted delivery were selected from a variety of classes intended to encompass the largest possible chemical compositions, namely flavonoids, aromatic acids, xanthones, terpenes, quinones, lignans and alkaloids. To the best of our knowledge, reviews on the nanoencapsulation of these phytochemicals and their delivery are not available. In this review, the issues associated with the limited use of each phytochemical in cancer therapy in humans are reviewed and the advantages of entrapment into nanocarriers are assessed in terms of drug loading efficiency, size of nanocarriers, drug release profiles and in vitro and/or in vivo testing specific to cancer research, e.g., cytotoxicity assay, cell inhibi- tion/viability, scavenging of reactive oxygen species and biodistribution studies (elimination half-life and mean residence time). KEYWORDS: Nanopharmaceutics, Phytochemicals, Chemotherapeutic, Drug Delivery Systems, Cancer Treatment. CONTENTS Introduction ................................... 2 Classes of Selected Phytochemicals .................... 3 Flavonoids .................................. 3 Flavonolignans ............................... 3 Stilbenes ................................... 4 Phenolic Acids ............................... 4 Quinones ................................... 5 Xanthones .................................. 5 Terpenoids .................................. 5 Lignans .................................... 5 Alkaloids .................................. 6 Phytochemicals: Molecular Targets and Mechanisms ......... 7 Antioxidant Activity ........................... 7 Inhibition of Oncogene Expression/Induction of Tumor Suppress Gene Expression ................... 8 Induction of Cell-Cycle Arrest ..................... 8 Induction of Apoptosis .......................... 8 Inhibition of Signal Transduction Pathway ............. 8 Inhibition of Cell Adhesion/Invasion/Metastasis .......... 8 Enzyme Induction/Inhibition ...................... 9 ∗ Author to whom correspondence should be addressed. Email: djhurry@uom.ac.mu Received: 14 January 2014 Accepted: 17 January 2014 Anti-Angiogenesis ............................. 9 Types of Commonly Used Nanocarriers ................. 9 Block Copolymer Nanomicelles .................... 9 Nanospheres and Nanocapsules .................... 9 Liposomes .................................. 9 Solid Lipid Nanoparticles/Nanostructured Lipid Carriers (SLNs or NLCs) .................................. 9 Encapsulation of Selected Phytochemicals ................ 10 Apigenin (Flavonoid) ........................... 10 Artemisinin and Dihydroartemisinin (Terpene) ........... 10 Berberine (Alkaloid) ........................... 11 Combretastatin-A4 (Flavonoid) ..................... 12 Ellagic Acid (Phenolic acid) ...................... 12 Emodin (Quinone) ............................. 12 Ferulic Acid (Phenolic acid) ...................... 13 Gambogic Acid (Xanthone) ....................... 13 Honokiol (Lignan) ............................. 13 Isoliquiritigenin (Terpene) ........................ 14 Lapachone (Quinone) ........................... 14 Luteolin (Flavonoid) ........................... 14 Nobiletin (Flavonoid) ........................... 15 Noscapine (Alkaloid) ........................... 15 Thymoquinone (Quinone) ........................ 15 Triptolide (Terpene) ............................ 16 Silymarin and Silybin (Flavonoid) ................... 17 Ursolic Acid and Oleanolic Acid (Terpene) ............. 17 Zerumbone (Terpene) ........................... 17 J. Biomed. Nanotechnol. 2014, Vol. 10, No. xx 1550-7033/2014/10/001/031 doi:10.1166/jbn.2014.1884 1