Biodegradable Vancomycin-eluting Poly[(d,l)-lactide-co-glycolide] Nanofibres for the Treatment of Postoperative Central Nervous System Infection

Abstract

The incidence of postoperative central nervous system infection (PCNSI) is higher than 5%–7%. Successful management of PCNSI requires a combined therapy of surgical debridement and long-term antibiotic treatment. In this study, Duraform soaked in a prepared bacterial solution was placed on the brain surface of rats to induce PCNSI. Virgin poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous membranes (vehicle-control group) and vancomycin-eluting PLGA membranes (vancomycin-nanofibres group) were implanted. The wound conditions were observed and serial brain MRI and pathology examinations were performed regularly. PCNSI was consistently induced in a single, simple step. In the vehicle-control group, most rats died within 1 week, and the survival rate was low (odds ratio = 0.0357, 95% confidence interval = 0.0057–0.2254). The wounds and affected cerebral tissues necrosed with purulence and increased in mass from the resulting PCNSI volumes. Initially, the mean PCNSI volumes showed no significant difference between the two groups. The PCNSI volume in the rats in the vancomycin-nanofibres group significantly decreased (P < 0.01), and the wound appearance was excellent. Pathologic examinations revealed that the necrosis and leukocyte infiltration area decreased considerably. The experimental results suggest that vancomycin-eluting PLGA nanofibres are favourable candidates for treating PCNSI after surgical debridement.

Treating Intracranial Abscesses in Rats with Stereotactic Injection of Biodegradable Vancomycin-Embedded Microparticles

“…PLGA is highly biocompatible and biodegradable, exhibits a wide range of degrade times, has tunable mechanical properties, and most notably, is an FDA-approved polymer. PLGA is among the most attractive polymeric candidates for fabricating devices for drug delivery and tissue engineering applications in the past two decades [14,38,39]. Degradation of PLGA results in lactic and glycolic acids, which lastly degrade into CO 2 and H 2 O [14,38].…”

“…PLGA is among the most attractive polymeric candidates for fabricating devices for drug delivery and tissue engineering applications in the past two decades [14,38,39]. Degradation of PLGA results in lactic and glycolic acids, which lastly degrade into CO 2 and H 2 O [14,38]. The 50:50 PLGA-based drug delivery carrier can sustainably release high concentrations of therapeutic agents to the target area for more than 8 weeks and result in minimal inflammatory reactions in the brain [14,40].…”

“…The distinct protective structure of the CNS also confines the delivery of therapeutic agents into the brain parenchyma. Many categories of systemic therapeutic agents, including antibiotics and chemotherapies, fail to reach effective levels in the CNS even while the systemic concentrations achieve toxic concentrations and severe side effects [14,15]. The instructed therapy period of parenteral antibiotic treatment for brain abscesses is prolonged, basically 4-8 weeks according to the treatment result and followed by neuroimaging [3,4,7].…”

Antimicrobial Nanostructures for Neurodegenerative Infections

“…Nanofibers are promising carrier molecules for the delivery of anticancer drugs. They are useful nanoparticles for postoperative local chemotherapy using surgical implantation of the scaffold (Tseng et al, 2013(Tseng et al, , 2015. These nanoparticles are able to protect the encapsulated drugs from enzymatic and hydrolytic degradation (Griffin et al, 2011;Wade et al, 2015).…”

Targeted concurrent and sequential delivery of chemotherapeutic and antiangiogenic agents to the brain by using drug-loaded nanofibrous membranes

“…32,33 Various drugs predominantly used to treat infections and cancers can easily be incorporated into these membranes and released at therapeutic dosages. 32,34 Targeted therapy…”