The increasingly complex treatment of bacterial infections, and its relevance in the clinical setting, requires the development of innovative strategies to improve patients' quality of life. In this context, polymeric microparticles represents a versatile drug delivery system (DDS) capable of improving the antibiotics' efficacy in the treatments, by loading drugs while modifying their release profile. In this study we aimed to produce polymeric microparticles by electrospraying using Poly-Butyl-Succinate (PBS), a biodegradable and biocompatible polyester. This versatile and easy-to-use technique enabled the incorporation of the poorly water-soluble Ciprofloxacin (CPX) into the polymer matrix. CPX is a fluoroquinolone antibiotic, inhibiting bacterial replication and effectively treating various infections. PBS is a well-known water-insoluble polymer with tuneable chemical-physical properties, also used for tissue regeneration and wound healing applications. An ex-vivo permeation study on porcine skin, serving as a model for human skin, was performed to assess potential enhancement in drug permeation. The microparticles were characterized by means of different techniques (SEM-EDX, XRD, ATR-FTIR, DSC), and their degradation rate was tested in DPBS and human plasma. Moreover, the as-produced DDS enabled the sustained release of CPX for several days, which proved effective against S. aureus and P. aeruginosa and also against a reference group of bacteria of skin microbiota often involved in pathological processes that make wounds chronic and difficult to heal. MIC and MBC assays were conducted using different culture media. Effective antibacterial activity was observed, along with inhibition of P. aeruginosa biofilm formation at sub-MIC concentrations.