Polyionic Complexed Antibacterial Heparin-Chitosan Particles for Antibiotic Delivery

Efficient delivery of antibacterial agents directly to sites of tissue injury faces challenges such as poor drug stability and fast degradation by biological mechanisms. Biocompatible nanocarrier systems can help sustain and control the delivery of antibacterial compounds while reducing the chances of antibacterial resistance or accumulation in unwanted tissues. In this study, we report the application of tailored polyionic particles via ionic interactions between negatively charged heparin and positively charge chitosan for efficient encapsulation of polyhexamethylene biguanide (PHMB) antibiotic. Negative zeta potential was required to encapsulate the positively charged PHMB. We demonstrate that the ratio of heparin to chitosan can be employed to create a tuned surface charge and maximize the bonding of the drug of choice as well as appropriate particle distribution and uniform morphology. Different formulations were evaluated in terms of size, polydispersity, surface charge, and morphology. Out of all these formulations, the best, negatively charged formulation at four-parts heparin to one-part chitosan was successfully encapsulated with PHMB and showed a sustained and controlled release in vitro for around 10 days. Reduced toxic responses (around 48% reduction) were observed from PHMB-loaded particles in contact with human dermal fibroblasts as compared to the soluble form of PHMB. Finally, in terms of antibacterial properties, the particles resulted in growth inhibition as well as the direct killing of both Gram-positive (Enterococcus faecalis) and Gram-negative (Escherichia coli) bacterial strains. The minimum inhibitory concentrations required to inhibit bacterial growth were determined by microplate dilution and LIVE/DEAD bacterial evaluation.