Abstract
The most suitable method to treat hydrocephalus disease is to insert a shunt catheter that drains the cerebral spinal fluid (CSF); however, shunt implantation is often associated with various bacterial infections. In this study, antibiotic-loaded nanospheres were prepared using the solvent evaporation technique and coated on an antibiotic-impregnated shunt surface to promote shunt antibacterial properties. Clindamycin (CDM) and rifampicin (RIF) were in combination loaded in a single nanosphere, whereas trimethoprim (TMP) was loaded individually in triblock copolymers [(d,l-lactide-random-ε-caprolactone)-block-poly(ethylene glycol)-block-(d,l-lactide-random-ε-caprolactone)] (PLEC). The drug-loading content, encapsulation efficiency, yield, size, and zeta potential of the antibiotic-loaded nanospheres were measured. The results showed that the drug-loading content of clindamycin- and rifampicin-loaded nanospheres (CDM/RIF-NPs) was approximately 3% and 8%, respectively, at a drug to polymer ratio of 1:2. In addition, trimethoprim-loaded nanospheres (TMP-NPs) showed nearly 7% drug loading at equal drug and polymer ratios. The amount of drug release was determined before and after the coating of nanospheres on the shunt surface. In addition, in silico molecular docking studies indicated the good chemical interaction of these antibiotics with PLEC, and the results were consistent with those of impregnation studies. Antibacterial tests of coated external ventricular drainage showed antibacterial activity for up to 21 days.