Real-time non-invasive monitoring of intravitreal drug release from porous silicon (pSi) by digital camera

Abstract

Purpose: It has been shown loading or removal drug from Porous Silicon (pSi) photonic crystals can shift the spectral peaks displayed by the crystal. We hypothesize this optical property can be harnessed for monitoring drug release in a living eye. The current study is to investigate the feasibility of non-invasive real-time monitoring of intravitreal drug release from pSi photonic crystals using digital imaging as a proof of concept study.

Methods: pSi oxide (pSiO2) microparticles were fabricated the test drugs rapamycin (Rap) or dexamethasone (Dex) was loaded via infiltration or covalent attachment methods. The rapamycin-infiltration loaded pSiO2 particles with k value 2.17 (2.17 pSiO2-inf Rap) were designed to appear with a color in the green region of the spectrum during drug release in the vitreous fluid, while particles with k value 2.45 (2.45 pSiO2-inf Rap) were designed to appear purple. Similar dexamethasone-covalent loaded pSiO2 particles were fabricated with k value of 2.17 (2.17 pSiO2-cov Dex) but after surface functionalization and covalent drug loading the particles appeared in the yellow region of the spectrum when in the vitreous. The above three types of drug loaded pSiO2 particles were intravitreally injected into one eye of 60 rabbits (~2 mg/eye) and serial fundus photos were acquired along with the drug levels in the vitreous over time. The total area of the expected color from the injected particles was correlated with the drug levels in the vitreous.

Results: The 2.17 pSiO2-inf Rap microparticles showed the least number of green particles initially in the rabbit vitreous, and the greenish particles become more visible over time. Similarly, 2.45 pSiO2-inf Rap microparticles showed a minimal number of purple colored particles immediately after injection. The purple particles became more visible over a period of 3 weeks as a first-order release of Rap was observed. In contrast, the covalently loaded Dex pSiO2 particles demonstrated a slower color shifting and sustained drug release mode with the yellowish particles faded over time in rabbit vitreous as the pSiO2 matrix degraded and Dex released. At longer times, the particles disappeared completely, presumably due to more extensive degradation of the nanostructure in the particles.

Conclusions: Rap and Dex release from pSi photonic crystals in rabbit vitreous may be quantitatively monitored using a digital fundus camera.

Keywords: 688 retina • 763 vitreous • 608 nanomedicine