Influence of PEGylated porous silicon nanoparticles on permeation and efflux of an orally administered antibiotic

Abstract

Advanced materials-based strategies are proving to be promising in solving the major problems of oral drug delivery. Herein, Polyethylene glycol (PEG)-functionalized porous silicon nanoparticles (pSiNPs) containing meropenem (MER) are proposed as a strategy to increase its transport across the intestinal epithelium, while maintaining its antibacterial activity. After surface conjugation of pSiNPs with TPGS (d-α-Tocopherol polyethylene glycol 1000 succinate) and NH2-PEG4-PA (amine PEG4 propionic acid), MER, a last-resort antibacterial drug, was loaded into these NPs with a loading capacity of 27–28.9 wt%. Cellular uptake results in LS174T cells demonstrate efficient cellular uptake of nanoparticles and show their potential to enable transcellular delivery of MER. The bioavailability of MER was significantly improved by all the prepared formulations (i.e., increased absorptive transport and reduced secretory transport). The MER-pSi-TPGS showed the best performance with an efflux ratio (i.e., secretory transport/absorptive transport) of 0.40 which is 5.5 folds less than pure MER (2.62). The in-vitro antibacterial assay showed that these formulations could retain MER's antibacterial activities against Staphylococcus aureus and Pseudomonas aeruginosa. Lastly, results from a modified Caco-2 monolayer model showed that both MER and MER-pSi-TPGS killed the bacteria after permeation, the rate of killing of MER-pSi-TPGS was rapid as compared to MER.

Keywords

• Meropenem
• Biomodulation
• Efflux
• Oral drug delivery
• PEGylation