We have developed a chemically-controlled drug delivery system in which a drug is covalently attached via a carbamate to hydrogel microspheres using a β-eliminative linker; rate-determining proton removal from a C-H bond adjacent to an electron withdrawing group results in a β-elimination to cleave the carbamate and release the drug. After subcutaneous injection of the hydrogel-drug conjugate, the drug is slowly released into the systemic circulation and acquires an elimination t1/2,β that matches the t1/2 of linker cleavage. A similar β-eliminative linker with a slower cleavage rate is installed into crosslinks of the polymer to trigger gel degradation after drug release. We have now prepared β-eliminative linkers that contain deuterium in place of the hydrogen whose removal initiates cleavage. In vitro model systems of drug release and degelation show large primary deuterium kinetic isotope effects of kH/kD˜2.5 to 3.5. Using a deuterated linker to attach the peptide octreotide to hydrogel-microspheres, the in vivo t1/2,β of the drug was increased from ˜1.5 to 4.5weeks in the rat. Similarly, the in vivo time to biodegradation of hydrogels with deuterium-containing crosslinks could be extended ˜2.5-fold compared to hydrogen-containing counterparts. Thus, the use of primary deuterium kinetic isotope effects in a single platform technology can control rates of β-elimination reactions in drug release and polymer biodegradation rates.