title: Hydrosilylated porous silicon particles function as an intravitreal drug delivery system for daunorubicin.
abstract: OBJECTIVE
  To evaluate in vivo ocular safety of an intravitreal hydrosilylated porous silicon (pSi) drug delivery system along with the payload of daunorubicin (DNR).
  
  
  METHODS
  pSi microparticles were prepared from the electrochemical etching of highly doped, p-type Si wafers and an organic linker was attached to the Si-H terminated inner surface of the particles by thermal hydrosilylation of undecylenic acid. DNR was bound to the carboxy terminus of the linker as a drug-loading strategy. DNR release from hydrosilylated pSi particles was confirmed in the excised rabbit vitreous using liquid chromatography-electrospray ionization-multistage mass spectrometry. Both empty and DNR-loaded hydrosilylated pSi particles were injected into the rabbit vitreous and the degradation and safety were studied for 6 months.
  
  
  RESULTS
  The mean pSi particle size was 30×46×15 μm with an average pore size of 15 nm. Drug loading was determined as 22 μg per 1 mg of pSi particles. An ex vivo drug release study showed that intact DNR was detected in the rabbit vitreous. An in vivo ocular toxicity study did not reveal clinical or pathological evidence of any toxicity during a 6-month observation. Hydrosilylated pSi particles, either empty or loaded with DNR, demonstrated a slow elimination kinetics from the rabbit vitreous without ocular toxicity.
  
  
  CONCLUSIONS
  Hydrosilylated pSi particles can host a large quantity of DNR by a covalent loading strategy and DNR can be slowly released into the vitreous without ocular toxicity, which would appear if an equivalent quantity of free drug was injected.
authors: Department of Ophthalmology, Jacobs Retina Center at Shiley Eye Center, University of California, San Diego, La Jolla, California 92093-0946, USA.
authors: Kathrin I
authors: KI
authors: Hartmann
authors: Alejandra
authors: A
authors: Nieto
authors: Elizabeth C
authors: EC
authors: Wu
authors: William R
authors: WR
authors: Freeman
authors: Jae Suk
authors: JS
authors: Kim
authors: Jay
authors: J
authors: Chhablani
authors: Michael J
authors: MJ
authors: Sailor
authors: Lingyun
authors: L
authors: Cheng
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D003630:Daunorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D016503:Drug Delivery Systems; D058449:Intravitreal Injections; D010316:Particle Size; D016062:Porosity; D011817:Rabbits; D012825:Silicon / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors; D059005:Topoisomerase II Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D059005:Topoisomerase II Inhibitors; D012825:Silicon; D003630:Daunorubicin