title: Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea.
abstract: OBJECTIVE
  Supplementation of exogenous nerve growth factor (NGF) into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route.
  
  
  METHODS
  A novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic(®) F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously.
  
  
  RESULTS
  Biological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane.
  
  
  CONCLUSIONS
  Data presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China ; Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Bu
authors.affiliation: School of Pharmacy, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Tang
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Wei
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Hongzhuo
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D001682:Biological Availability; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D003460:Crystallization; D005233:Fatty Alcohols / Q000737:chemistry*; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D020932:Nerve Growth Factor / Q000493:pharmacokinetics* / Q000494:pharmacology; D016716:PC12 Cells; D010316:Particle Size; D051381:Rats; D012405:Round Window, Ear / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D055672:Static Electricity; D014961:X-Ray Diffraction
chemical_list: D005233:Fatty Alcohols; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol; D020932:Nerve Growth Factor
keywords: PC12 cells; bioavailability; inner ear drug delivery; lipid-based crystalline nanoparticles; nerve growth factor