Antibiotic impregnation and nanocoating of external ventricular drainage catheters for antibacterial applications: Evaluation of in vitro studies and molecular docking.

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.

Antibacterial and biocompatibility studies of triple antibiotics-impregnated external ventricular drainage: In vitro and in vivo evaluation.

Hydrocephalus is a neurological disease caused by an unusually high level of cerebrospinal fluid (CSF), which can be relieved by external ventricular drainage (EVD) insertion. However, the infection can lead to complications during the use of EVD. In this study, EVD was impregnated with three synergistic antibiotics, including rifampicin, clindamycin, and trimethoprim, to improve the antibacterial property. The impregnated drainage was studied for its characteristics in vitro and in vivo. Drug loading determination revealed that rifampicin had the highest concentration in the tube, followed by clindamycin and trimethoprim, respectively. In vitro cytotoxicity and hemolytic studies showed no toxic effects from antibiotics-impregnated EVD on fibroblast and red blood cells. For antibacterial testing, the impregnated EVD exhibited antibacterial activity against Staphylococcus aureus MRSA and Staphylococcus epidermidis up to 14 and 90 days, respectively. Moreover, biocompatibility and drug release into the bloodstream and surrounding tissues were investigated by implantation in rabbits for 30 days. Histology and morphology results showed that fibroblast cells began to adhere to the drainage surface and inflammatory cell numbers were noticeably small after the long-term implantation. In addition, there was no drug leakage to the bloodstream and surrounding tissues. Hence, this impregnated EVD can potentially be used for antibacterial application.

Inflammation-responsive nanocapsules for the dual-release of antibacterial drugs.

Herein, we design inflammation-responsive nanocapsules containing two antibiotics. The releases are programmed to be triggered under conditions occurring at the different stages of wound healing. The nanocapsules exhibit excellent antibacterial activities against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Incorporation of small amounts of nanocapsules in hydrogels leads to efficient antibacterial wound dressings.