title: Lipid-dendrimer hybrid nanosystem as a novel delivery system for paclitaxel to treat ovarian cancer.
abstract: Combining lipids and dendrimers into one formulation is an emerging platform in the drug delivery field. This study aims to (i) develop and characterize a lipid-dendrimer hybrid (LDH) nanosystem for the hydrophobic anticancer drug paclitaxel, and (ii) evaluate its in vitro and in vivo anti-cancer activity in ovarian cancer models. The LDH nanosystems were prepared from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and poly (amidoamine) (PAMAM) G4.0. The size and zeta potential of the LDH nanosystem were 37.6 ± 6.1n m and +2.9 ± 0.1 mV, respectively, with vesicular morphology observed under cryo-TEM. The encapsulation efficiency of paclitaxel in the LDH system was 78.0 ± 2.1%. The potency of paclitaxel could be significantly improved by 37-fold when presented in the LDH nanosystem as compared to free drug, whereby paclitaxel and PAMAM G4.0 acted synergistically in killing the ovarian cancer cells. As shown by fluorescence confocal microscopy, majority of the lipids in the LDH nanosystem were located in the plasma membrane, while the dendrimers were distributed intracellularly upon uptake. Despite the use of a 10-fold lower paclitaxel dose, the survival of IGROV-1 ovarian tumor-bearing animals could be significantly prolonged by the paclitaxel-loaded LDH nanosystem, as reflected by a 50% increase in the median survival time. Such hybrid nanosystem emerged from combining two established drug delivery platforms could pave way for the development of multifunctional delivery systems for potential theranostic applications.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Ng
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Ming R
authors.initials: MR
authors.lastname: Toh
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore. Electronic address: phacncg@nus.edu.sg.
authors.forename: Gigi N C
authors.initials: GNC
authors.lastname: Chiu
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D006801:Humans; D016513:Mice, SCID; D053758:Nanoparticles; D036103:Nanotechnology; D009757:Nylons / Q000737:chemistry* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050091:Dendrimers; D004337:Drug Carriers; D009757:Nylons; C520550:PAMAM-G4; D015060:1,2-Dipalmitoylphosphatidylcholine; C081581:colfosceril palmitate; D017239:Paclitaxel
keywords: Dendrimer; Drug delivery system; Lipid; Liposome; Ovarian cancer; Paclitaxel