Polyvinylpyrrolidone-drug conjugate: synthesis and release mechanism.
Covalent conjugates of polyvinylpyrrolidone (PVP) with para-nitroaniline (PNA) were synthesized as a model PVP-drug conjugate, and PNA release was evaluated in vitro. Pyrrolidone ring opening with subsequent t-BOC protection of the pyrrolidone nitrogen and reaction with PNA in methylene chloride (CH2Cl2) produced a PVP-PNA conjugate with 3% of the pyrrolidone groups modified. Rates of PNA release from N-deprotected conjugates were twofold greater than those that were N-protected, indicating participation of the pyrrolidone N in release. Additional studies with monomeric analogs supported intramolecular base catalysis rather than lactam formation as the mechanism of this involvement. The approach serves as a prototype for the conjugation of other drugs with primary and secondary amine functional groups with PVP, including peptides and proteins.
D'Souza
Ajit Joseph M
AJ
Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave., Lawrence, KS 66047, USA.
Schowen
Richard L
RL
Topp
Elizabeth M
EM
D002626:Chemistry, Pharmaceutical; D011205:Povidone / Q000138:chemical synthesis* / Q000493:pharmacokinetics*
D011205:Povidone