Tailoring the degradation kinetics of mesoporous silicon structures through PEGylation

Abstract

Injectable and implantable porosified silicon (pSi) carriers and devices for prolonged and controlled delivery of biotherapeutics offer great promise for treatment of various chronic ailments and acute conditions. Polyethylene glycols (PEGs) are important surface modifiers currently used in clinic mostly to avoid uptake of particulates by reticulo-endothelial system (RES). In this work we show for the first time that covalent attachment of PEGs to the pSi surface can be used as a means to tune degradation kinetics of silicon structures. Seven PEGs with varying molecular weights (245, 333, 509, 686, 1214, 3400, and 5000 Da) were employed and the degradation of PEGylated pSi hemispherical microparticles in simulated physiological conditions was monitored by means of ICP-AES, SEM, and fluorimetry. Biocompatibility of the systems with human macrophages in vitro was also evaluated. The results clearly indicate that controlled PEGylation of silicon microparticles can offer a sensitive tool to finely tune their degradation kinetics and that the systems do not induce release of proinflammatory cytokines IL-6 and IL-8 in THP1 human macrophages.

Figure 1

Schematic presentation of chemical modification of pSi microparticles with APTES and PEG molecules.

Figure 2

Degradation kinetics of large pores (pores size 30–50nm) and small pores (10nm) Si microparticles as evaluated by ICP-AES. The degradation kinetic profile is expressed as a percentage of the total Si contents released to the degradation medium.

Figure 3

Degradation kinetics of large pores PEGylated pSi microparticles as evaluated by ICP-AES. The degradation kinetic profile is expressed as a percentage of the total Si contents released to the degradation medium: (A) PBS pH 7.2; (B) Fetal Bovine Serum (FBS).

Figure 3

Degradation kinetics of large pores PEGylated pSi microparticles as evaluated by ICP-AES. The degradation kinetic profile is expressed as a percentage of the total Si contents released to the degradation medium: (A) PBS pH 7.2; (B) Fetal Bovine Serum (FBS).

Figure 4

Comparison between the experimental data (dots) and the best fitting power laws αt^β for the first phase of the degradation process according to scaling low M_t =α·t^β

Figure 5

SEM images of the pSi particles during the degradation process in PBS pH 7.2. Systems shown: a) APTES particles; b) Particles modified with PEG 861; c) Particles modified with PEG 5000. Timepoints: 2, 8, 18 and 48 hours.

Figure 6

Erosion of fluorescent PEG vs low MW probe from the pSi particle surface as followed up by fluorimetry in the degradation medium in PBS and FBS. The degradation kinetic profile is expressed as a percentage of the total fluorescence released to the degradation medium at 72 hours.

Figure 7

Release of proinflammatry cytokines IL-6 and IL-8 by human cultured THP-1 macrophages following incubation with pSi particles with various surface modifications.