Zero-Order Kinetics Release of Lamivudine from Layer-by-Layer Coated Macromolecular Prodrug Particles

To reduce the risk of side effects and enhance therapeutic efficiency, drug delivery systems that offer precise control over active ingredient release while minimizing burst effects are considered advantageous. In this study, a novel approach for the controlled release of lamivudine (LV) was explored through the fabrication of polyelectrolyte-coated microparticles. LV was covalently attached to poly(ε-caprolactone) via ring-opening polymerization, resulting in a macromolecular prodrug (LV-PCL) with a hydrolytic release mechanism. The LV-PCL particles were subsequently coated using the layer-by-layer (LbL) technique, with polyelectrolyte multilayers assembled to potentially modify the carrier’s properties. The LbL assembly process was comprehensively analyzed, including assessments of shell thickness, changes in ζ-potential, and thermodynamic properties, to provide insights into the multilayer structure and interactions. The sustained LV release over 7 weeks was observed, following zero-order kinetics (R2 > 0.99), indicating a controlled and predictable release mechanism. Carriers coated with polyethylene imine/heparin and chitosan/heparin tetralayers exhibited a distinct increase in the release rate after 6 weeks and 10 weeks, respectively, suggesting that this coating can facilitate the autocatalytic degradation of the polyester microparticles. These findings indicate the potential of this system for long-term, localized drug delivery applications, requiring sustained release with minimal burst effects.