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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. doi: https://doi.org/.
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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.
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.
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).
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.
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