In this study, we describe the synthesis of an amine-modified acetalated dextran polymer, which is combined with heparin (HP) as the basis for a novel controlled release system. Dextran-amine (DEXAM) conjugates, synthesised using reductive amination, were incorporated into DEXAM/HP microspheres. HP binds to positively charged ammonium ions of the DEXAM conjugates, contributing to the structural integrity of the microspheres. Crystal violet (CV) was encapsulated inside DEXAM/HP microspheres as a model drug to test the system. Protamine with a high affinity for HP functioned as a trigger to release CV. DEXAM/HP microspheres were characterised by particle size, encapsulation efficiency, scanning electron microscope images, and in vitro release profile. Release of CV from microspheres varied with primary amine content of DEXAM conjugates, amount of HP, and concentration of protamine added. The system is considered for controlled delivery of agents without the necessity of chemical modification.