Fabrication of pH-responsive smart films from P(3HB-co-4HB) and acetal-modified dextran for controlled drug release

• Biodegradable, pH-responsive films developed using P(3HB-co-4HB)/AcDex blends. • AcDex enhances film transparency, stiffness, and acid-triggered porosity. • pH-responsive films achieve up to 68% drug release within 24 h at pH 5.0. • Drug release is tunable via AcDex content, acetal type, and film thickness. • Release follows non-Fickian kinetics driven by AcDex hydrolysis and matrix erosion. Leveraging the biodegradability and biocompatibility of polyhydroxybutyrate (PHB), this study develops pH-responsive drug delivery films by blending P(3HB- co -4HB) copolymer with acetal-modified dextran (AcDex) via solvent casting. AcDex reduces the crystallinity of P(3HB- co -4HB), increasing stiffness while reducing ductility. The film’s mechanical properties exhibit distinct pH-dependent behaviour: under acidic conditions (pH 5.0), AcDex hydrolysis induces pore formation and reduces mechanical strength, while minimal changes occur at neutral pH (7.4). Exploiting the film’s pH-triggered hydrolysis characteristic, Rhodamine B (RhB) was encapsulated as a model drug to assess release kinetics and understand how significantly it is influenced by film thickness, AcDex content, acetalation degree, and acyclic-to-cyclic acetal ratio. Under acidic conditions, the films demonstrate up to a 6.0-fold increase in RhB release within 24 h compared to neutral pH. These results highlight the potential of AcDex/P(3HB- co -4HB) films as pH-responsive drug delivery systems.