Fabrication of biodegradable polycaprolactone/chitosan nanoparticle/sodium alginate-based tablet implants for controlled doxorubicin release

Abstract

Controlled drug delivery plays a critical role in modern pharmaceutics, enabling precise and sustained therapeutic effects. This study presents the development of biodegradable composite implants composed of polycaprolactone (PCL), sodium alginate (SA), and chitosan (CS) nanoparticles loaded with doxorubicin (CS-DOX) for long-term, localized cancer therapy. CS-DOX nanoparticles were synthesized via ionic gelation, achieving an encapsulation efficiency of approximately 80%, while 10 µm PCL microparticles were produced using spray drying to form a uniform implant matrix. In this work, tablet implants containing 5, 7, and 10 wt% DOX were fabricated using a 5 mm diameter mold under compression, with an appropriate amount of SA used as a binder. DLS analysis revealed nanoparticle sizes of ~ 110 nm for CS and ~ 135 nm for CS-DOX, with zeta potentials decreasing from + 28 mV (CS) to + 23 mV (CS-DOX), confirming colloidal stability. Drug release studies exhibited a biphasic profile, consisting of an initial burst release followed by sustained release over 15 days. In all fabricated implants containing DOX, the drug release kinetics followed the Korsmeyer–Peppas model. MTT assays on 4T1 breast cancer cells demonstrated an ~ 70% reduction in viability after 72 h for the 10% DOX-loaded implant. These findings highlight the potential of PCL/SA/CS-DOX implants as an effective biodegradable system for localized drug delivery, offering tunable release kinetics and enhanced therapeutic outcomes. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.