title: Dendrimer-stabilized smart-nanoparticle (DSSN) platform for targeted delivery of hydrophobic antitumor therapeutics.
abstract: OBJECTIVE
  To formulate dendrimer-stabilized smart-nanoparticle (DSSN; pD-ANP-f) for the targeted delivery of the highly hydrophobic anticancer drug, Paclitaxel (PTXL).
  
  
  METHODS
  The developed nanoformulations were evaluated for particle size, surface-charge, loading efficiency, particle density, in-vitro drug release, SEM/TEM, cytotoxicity assay, fluorescence uptake, HPLC quantitative cell uptake assay, flow cytometry, tubulin polymerization, and stability assessments.
  
  
  RESULTS
  The developed pD-ANP-f nanoformulation (135.17 ± 7.39 nm; -2.05 ± 0.37 mV and 80.11 ± 4.39% entrapment) exhibited a pH-dependent drug release; remained stable in physiological pH, while rapid releasing PTXL under tumorous environment (pH 5.5). The cytotoxicity assay performed in cervical, breast, blood, and liver cancer cell lines showed pD-ANP-f to be strongly suppressing the growth of cancer cells. We investigated the fluorescence based intracellular trafficking and HPLC based cellular uptake of nanoformulated drug and the result indicates higher cellular uptake of pD-ANP-f compared to other formulations. pD-ANP-f prominently induced apoptosis (73.11 ± 3.84%) and higher polymerization of tubulins (59.73 ± 6.22%). DSSN nanoformulation was found to be extremely biocompatible (<1% hemolytic) compared to naked PTXL (19.22 ± 1.01%) as well as PTXL-dendrimer nanocomplex (8.29 ± 0.71%).
  
  
  CONCLUSIONS
  DSSN strategy is a novel and promising platform for biomedical applications that can be effectively engaged for the delivery of drug/gene/siRNA targeting.
authors.affiliation: Preclinical Nuclear Imaging Laboratory, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75390, USA, rakeshtekade@gmail.com.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Tekade
authors.forename: Muktika
authors.initials: M
authors.lastname: Tekade
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Abhay S
authors.initials: AS
authors.lastname: Chauhan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D050091:Dendrimers / Q000737:chemistry* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004355:Drug Stability; D006461:Hemolysis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D007700:Kinetics; D061986:MCF-7 Cells; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles; D036103:Nanotechnology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D050257:Tubulin Modulators; D017239:Paclitaxel