Synthesis, characterization and application of poly(ε-caprolactone-co-2-ethyl-2-oxazoline) as a carrier for procaine: microsphere formulation, drug release, and antimicrobial activity.

The aim of this study was to prepare procaine-loaded microspheres using a biodegradable poly(ε-caprolactone-co-2-ethyl-2-oxazoline) copolymer. The copolymer was synthesized from poly(ε-caprolactone) and 2-ethyl-2-oxazoline (CP) under thermal conditions and characterized by 1H NMR, FTIR, and DSC-ATG, while the microspheres (MS) were formulated via an oil-in-water solvent evaporation method and characterized using FTIR, XRD, SEM, particle-size analysis, drug loading, encapsulation efficiency, and in vitro release. The antimicrobial activity was tested on pure procaine (PR), CP, and MS to compare their resistance. The prepared microspheres achieved an encapsulation efficiency of 80.27%, with a Sauter diameter (d32) of 250 µm and rough globular-ovoid morphology. FTIR and XRD confirmed preservation of the copolymer structure, weak physical interactions between procaine and the polymer matrix, and reduced drug crystallinity suggestive of molecular dispersion. In vitro release studies revealed a biphasic profile with 94% cumulative release, best described by the Higuchi model, with Korsmeyer-Peppas analysis indicating anomalous non-Fickian transport, and antimicrobial assays demonstrated strain-dependent inhibitory activity.