Incorporation and Controlled Release of Silyl Ether Prodrugs from PRINT Nanoparticles

Abstract

Asymmetric bifunctional silyl ether (ABS) prodrugs of chemotherapeutics were synthesized and incorporated within 200 nm x 200 nm particles. ABS prodrugs of gemcitabine were selected as model compounds because of the difficulty to encapsulate a water soluble drug within a hydrogel. The resulting drug delivery systems were degraded under acidic conditions and were found to release only the parent or active drug. Furthermore, changing the steric bulk of the alkyl substituents on the silicon atom could regulate the rate of drug release and therefore the intracellular toxicity of the gemcitabine-loaded particles. This yielded a family of novel nanoparticles that could be tuned to release drug over the course of hours, days, or months.

Engineered PRINT® nanoparticles for controlled delivery of antigens and immunostimulants

“…Active components can be varied widely as well and include oligonucleotides, 9-11 RNA, 12,13 polysaccharides, proteins, 6,13,14 and small molecules 11,[15][16][17] that can serve as antigens or immunomodulators. The particle matrix can be composed entirely of active components or selective inert materials such as poly(lactic-co-glycolic) acid (PLGA), 6 or polyethylene glycol (PEG) hydrogels 7 that serve as bulking agents to reduce costs.…”

Di-tert-butylsilyl Bis(trifluoromethanesulfonate)

“…8 (G) Asymmetric bifunctional silyl ether (ABS) prodrugs of chemotherapeutics (camptothecin, dasatinib, and gemcitabine) were obtained in one step by reacting a dichlorodialkyl silane (i-Pr, Et,) or tBu 2 Si(OTf) 2 with the pendant alcohol on the chemotherapeutic. 9 This kind of combination of a silyl ether, a chemotherapeutic and a polymerizable monomer ensures protection for the drugs and decreases the rate of degradation. …”

Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine

“…For some time now, NPs such as micelles and metals (Au, Ag, or Cu) have been used as carriers to aid in the delivery of anticancer drugs. In the case of GEM, there have been various attempts to deliver the drug to the tumor cells using micellar NPs, 12,22 dendrimeric and polymer NPs, 16,31 and magnetic NPs. [32][33][34] Here, we present a method for delivering the drug that offers mitigation of the drug's side effects, as well as a targeted delivery and controlled release of the drug, to improve its overall efficacy.…”