June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
PLGA capsulated porous silicon particles for sustained intravitreal delivery of daunorubicin
Author Affiliations & Notes
  • Kaihui Nan
    Department of Ophthalmology, Jacobs Retina Center at University of California, San Diego, CA
  • Feiyan Ma
    Department of Ophthalmology, Jacobs Retina Center at University of California, San Diego, CA
  • Huiyuan Hou
    Department of Ophthalmology, Jacobs Retina Center at University of California, San Diego, CA
  • William Freeman
    Department of Ophthalmology, Jacobs Retina Center at University of California, San Diego, CA
  • Michael Sailor
    Department of Chemistry and Biochemistry, University of California, San Diego, CA
    Department of Bioengineering, University of California, San Diego, CA
  • Lingyun Cheng
    Department of Ophthalmology, Jacobs Retina Center at University of California, San Diego, CA
  • Footnotes
    Commercial Relationships Kaihui Nan, None; Feiyan Ma, None; Huiyuan Hou, None; William Freeman, OD-OS, Inc. (C); Michael Sailor, Spinnaker Biosciences (I); Lingyun Cheng, Spinnaker Biosciences (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1070. doi:
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    • Get Citation

      Kaihui Nan, Feiyan Ma, Huiyuan Hou, William Freeman, Michael Sailor, Lingyun Cheng; PLGA capsulated porous silicon particles for sustained intravitreal delivery of daunorubicin. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1070.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

Daunorubicin (DNR) is a FDA approved antiproliferation agent which has been used to treat proliferative vitreoretinopathy (PVR). However its narrow therapeutic window and short vitreous half-life limit its intraocular application. We have shown that adsorption loading of DNR into porous silicon (pSi) particles can provide a 2-week release in rabbit vitreous. However, DNR release was still fast and caused retinal toxicity. In the current study we aimed to develop a better controlled vitreous release system using PLGA capsulizing DNR loaded pSi particles.

 
Methods
 

Fresh etched porous silicon film was sonicated to produce pSi microparticles. pSi particles were oxidized at 800 degree C. DNR was absorbed into the pSi particles by soaking 10 mg pSi in 300 µL of 5mg/mL DRN solution overnight at room temperature. The drug loading was quantitated by thermogravimetric analysis (TGA). The DNR loaded pSi particles were divided into two groups: group 1 with PLGA (poly (lactic-co-glycolic acid) coating and group 2 without. For PLGA coating, DRN loaded pSi particles were allocated into 10% PLGA dichloromethane solution and vortex for 20 min. The mixture was dispersed into 2% PVA (polyvinyl alcohol) aqueous solution for evaporation of dichloromethane. PLGA coated particles were characterized under a light microscopy for PLGA capsulation. The particles with or without PLGA were allocated each into three closed vial with 1.5 mL of DPBS and incubated under 37°C on a mini labroller. At designated time points, 1mL supernatant was collected and the same amount of DPBS was added back into the vial. DNR in the supernatant was quantitated using a fluorescence spectrophotometer.

 
Results
 

The DNR loading into pSi particles was determined to be 32.99 µg/mg. Light microscopy showed 80% pSi particles were capsulated by PLGA and the non-capsulated pSi particles had a mean diagonal size of 75 µm (median 68.4 µm). DNR release from pSi without PLGA capsulation demonstrated a predicted peak concentration of 7200 ng/mL while only 1200 ng/mL for PLGA capsulated pSi. The DNR release profile from pSi particles was typical first-order kinetics while a sustained release mode was achieved through PLGA capsulation (Figure).

 
Conclusions
 

PLGA capsulation can slow down DNR release from pSi particles and reduce the initial burst release as well as improve the drug release kinetics optimized toward intravitreal drug delivery application.

  
Keywords: 503 drug toxicity/drug effects • 608 nanomedicine  
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