Credit: © 2010 ACS

Silyl ether groups, typically used to protect alcohol functions in organic synthesis, offer good control over the rate and mechanism of their cleavage through judicious choice of silicon substituents. Now, Joseph DeSimone and co-workers from the University of North Carolina have used this tunable stability to prepare acid-sensitive materials that show promise for medical devices1.

Four bifunctional silyl ethers (CO–Si(R)2–OC, where R is a methyl, ethyl, isopropyl or tert-butyl group) bearing a terminal acrylate moiety on each side chain were crosslinked and subsequently moulded into particles with well-defined morphologies. The behaviour of cubic microparticles loaded with the drug Rhodamine B was monitored in acidic solutions, at pH 5.0, 6.0 and 7.4 to respectively mimic lysosomal, endosomal and physiological environments. Using methyl, ethyl or isopropyl as substituents led to a drug release within hours, days or months, respectively. For each compound, degradation was much slower at higher pH.

In a different experiment, 'hexnut'-shaped nanoparticles, easily recognizable in cellular environments, were tagged with fluorescent dyes and incubated in HeLa cell lines. Transmission electron and laser scanning confocal microscopies revealed that the methyl-substituted particles rapidly decayed inside the cells — through swelling, fragmentation and degradation — but not outside, whereas tert-butyl-substituted ones remained intact in both environments. All four crosslinkers showed minimal toxicity for two different cell lines, rendering this acid-sensitive chemistry attractive for various in vivo applications, not only for drug release but also tissue engineering, suture or stents.