title: Functionalized mesoporous silica nanoparticle-based drug delivery system to rescue acrolein-mediated cell death.
abstract: OBJECTIVE
  Mesoporous silica nanoparticles (MSNs) were prepared and characterized to develop a drug delivery system by loading them with hydralazine and functionalizing them with polyethylene glycol. These agents restore damaged cell membranes and ameliorate abnormal mitochondria behavior induced by the endogenous toxin acrolein. Such a formulation shows potential as a novel therapeutic agent.
  
  
  CONCLUSIONS
  MSNs with encapsulated hydralazine and covalently linked with polyethylene glycol were subsequently synthesized and characterized by transmission-electron microscopy, N(2) adsorption/desorption, x-ray diffraction and UV-vis spectroscopy. MSNs exhibited large surface area, pore volume and tunable pore size. The mean particle size was 100 nm and hydralazine encapsulation efficiency was almost 25%. These were tested using PC12 in culture to restore their disrupted cell membrane and to improve mitochondria function associated with oxidative stress after exposure to acrolein. Lactate dehydrogenase, MTT, ATP and glutathione assays were used to examine the physiological functioning of the samples and the loss of lactate dehydrogenase from the cytoplasm assayed the integrity of the membranes. These evaluations are sufficient to initially demonstrate drug delivery (concentrated hydralazine) into the compromised cells cytoplasm using the MSNs as a vehicle.
  
  
  CONCLUSIONS
  MSNs modified with drug/polymer constructs provide significant neuroprotection to cells damaged by a usually lethal exposure to acrolein.
authors.affiliation: Purdue University, Center for Paralysis Research, School of Veterinary Medicine, West Lafayette, IN 47907, USA.
authors.forename: Youngnam
authors.initials: Y
authors.lastname: Cho
authors.forename: Riyi
authors.initials: R
authors.lastname: Shi
authors.forename: Richard B
authors.initials: RB
authors.lastname: Borgens
authors.forename: Albena
authors.initials: A
authors.lastname: Ivanisevic
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D004705:Endocytosis; D006830:Hydralazine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D016716:PC12 Cells; D011092:Polyethylene Glycols / Q000737:chemistry*; D016062:Porosity; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D006830:Hydralazine; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D000171:Acrolein