5-Fluorouracil Encapsulation in PLA Films: The Role of Chitosan Particles in Modulating Drug Release and Film Properties

The development of effective drug delivery systems, in terms of their application route and release profile, is crucial for improving the therapeutic outcomes of all bioactive compounds. In this study, we explored the encapsulation of 5-fluorouracil, a commonly used chemotherapeutic agent, in poly(lactic acid) films for the first time and the role of chitosan particles in the structure, as no previous studies have examined their potential for this purpose. The objective is to enhance the sustained release of 5-FU and minimise the burst release step while leveraging the biocompatibility and biodegradability of these polymers. PLA films were fabricated using a solvent casting method, and 5-FU was encapsulated either directly within the PLA matrix or loaded into chitosan particles, which were then incorporated into the film. The physicochemical properties of the films, including morphology, wettability, phase state of the drug, thermal stability, drug loading efficiency, and release kinetics, were evaluated along with their barrier and mechanical properties. The results indicate a change in morphology after the addition of the drug and/or particles compared to the empty film. Additionally, the strain value at break decreased from nearly 400% to below 15%. Young’s modulus also changes from 292 MPa to above 500 MPa. The addition of chitosan particles lowered the permeability and vapour transmission rate slightly, while dissolving 5-FU increased them to 241 g/m2·24 h and 1.56 × 10−13 g·mm/m2·24 h·kPa, respectively. Contact angle and surface energy values went from 71° and 34 mJ/m2 for pure PLA to below 53° and around 58 mJ/m2 for the composite structures, respectively. Drug release tests, conducted for 8 h, indicated a nearly 2-fold decrease in the amount of drug released from the film with particles within this period, from around 45% for bare particles and PLA film to 25% for the combined structure, indicating the potential of this system for sustained release of 5-FU.