A new aliphatic amino prodrug system for the delivery of small molecules and proteins utilizing novel PEG derivatives.
A new amino PEG prodrug system, based entirely on aliphatic structures, has been designed using ester derivatives easily synthesized from N-modified bis-N-2-hydroxyethylglycinamides. Hydrolysis of the various promoiety bonds, in vivo, regenerated amine in a predictable manner. Thus, a novel new methodology for controlled release of amino-containing drugs, peptides, and proteins has been accomplished. This work demonstrates the usefulness of a PEG prodrug strategy that results in solubilization of insoluble amino-containing drugs and provides prodrugs with relatively long circulating half-lives. It can be appreciated that this novel system should also be applicable for nonpolymer-containing prodrugs as well.
Greenwald
Richard B
RB
Enzon Pharmaceuticals Inc., 20 Kingsbridge Road, Piscataway, New Jersey 00854, USA. richard.greenwald@enzon.com
Zhao
Hong
H
Yang
Karen
K
Reddy
Prasanna
P
Martinez
Anthony
A
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D004952:Esters; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D006207:Half-Life; D006868:Hydrolysis; D066298:In Vitro Techniques; D009113:Muramidase / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011506:Proteins / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship
D000588:Amines; D004952:Esters; D011355:Prodrugs; D011506:Proteins; D011092:Polyethylene Glycols; D009113:Muramidase; D005998:Glycine