Shell-sheddable antibiotic nanohybrid through drug-mediated surface-initiated polymerization: an overcoat approach for modulated burst release

Antibiotic-impregnated bioactive therapeutic biomaterials are highly demanding due to the risk of infection associated with musculoskeletal injuries and bone replacement surgeries. In this study, we report the synthesis of antibiotic nanohybrid having an aqueous sensitive sheddable polycaprolactone (PCL) shell grafted over gentamicin sulphate (GS)-charged bioactive glass (BG) nanospheres via surface-initiated polymerization. This study indeed shows the additional role of GS, while its potential as an initiator for the ring opening polymerization of epsilon-caprolactone (CL) is investigated by choosing 1:0.175 and 1:0.53 weight ratio of CL:GS-loaded nanoparticles. The influence of monomer/initiator feed ratio on the synthesized PCL was evident in the unbound PCL fractions, suggesting the effective role of GS as an initiator. However, in the nanohybrids, the percentage grafting and shell thickness were comparable regardless of the quantity of drug-loaded particles used. The H-1 NMR and MALDI-ToF analysis of the unbound PCL further confirmed the part of GS with the hydroxyl end group served as the surface anchoring group. The successful grafting of PCL was confirmed by different characterization techniques. The effective shedding of the shell in the aqueous environment and the subsequent release of GS were confirmed by the TEM analysis and zeta potential measurements. Additionally, the drug release was modulated with controlled burst release with only 15 wt% and 14 wt% release in the nanohybrids in the first 8 h, while it is 29 wt% for the unmodified BG nanoparticles. Studies of growth inhibition of clinically relevant strains such as E.coli, S.aureus, P.aeruginosa and B.subtilis indicated that the GS released from the nanohybrid retained antibacterial activity. Thus the GS-initiated polyester functionalization of drug-loaded BG nanoparticles, which enables an environment responsive as well as modulated release, is considered beneficial for further progresses in drug-loaded scaffolds.