Suitability of porous silicon microparticles for the long-term delivery of redox-active therapeutics

Abstract

Thermal oxidation of porous Si microparticles provides an inert carrier for the long-term release of the anthracycline drug daunorubicin. Without prior oxidation, porous Si undergoes an undesirable side reaction with this redox active drug.

Hydrosilylated Porous Silicon Particles Function as an Intravitreal Drug Delivery System for Daunorubicin

“…To determine the amount of DNR loaded, pSi microparticles were completely dissolved in a solution of 1 M sodium hydroxide (Sigma-Aldrich) and the solution was neutralized with 1 M hydrochloric acid (Sigma-Aldrich) to recover the fluorescence spectrum of the free drug as previously described. 26 The calculated quantity of DNR loaded was 22 mg per 1 mg of pSi particles. 13 …”

“…In our previous in vitro study, reduced DNR was observed, and the degradation products from this hydrosilylated pSi delivery system showed increased potency toward RPE cells. 26 In the present in vivo study, the same delivery system and the payload did not induce any signs of ocular toxicity or other deleterious effects during 6 months of the study. It is known that pSi degrades into silicic acid, which is presumably cleared with physiological vitreous fluid turnover.…”

“…This effect was proposed to be caused by accelerated DNR reduction by Si-H species on pSi microparticles. 26 The increased potency may improve the therapeutic index if the highest nontoxic dose remains the same. Since the drug will be delivered along with the pSi particles, an in vivo safety study using DNR-loaded pSi particles would be the immediate further effort to evaluate this drug and the delivery system.…”

“…We hypothesize that the released DNR experienced chemical reduction in the biological fluid 27 (excised vitreous) and Si-Si or Si-H species in the pSi carrier may have accelerated this reduction process. 26 In addition, accumulation of silicic acid in the ex vivo static dissolution study (excised vitreous) may have further aggravated drug degradation. It is not clear if this degree of degradation will be observed in a living eye, where the vitreous fluid is dynamic and silicic acid and other silicon-related byproducts may not accumulate to the extent that is reached in a quiescent test tube.…”

Surface Engineering of Porous Silicon Microparticles for Intravitreal Sustained Delivery of Rapamycin

“…This procedure results in a functional pSi surface grafted with C-10 alkyls containing terminal carboxyl groups (-COOH). A significant quantity of the surface hydrides (Si-H) remaining after the hydrosilylation reaction were eliminated by air oxidation at 150 °C for 48 hours in a ceramic boat inside a muffle furnace (Thermo Fisher Scientific, Pittsburg, PA), as previously described 23 . The functionalized samples were kept under vacuum in a desiccator.…”