Sustained release of vancomycin from novel biodegradable nanofiber-loaded vascular prosthetic grafts: in vitro and in vivo study

Abstract

This study describes novel biodegradable, drug-eluting nanofiber-loaded vascular prosthetic grafts that provide local and sustained delivery of vancomycin to surrounding tissues. Biodegradable nanofibers were prepared by first dissolving poly(D,L)-lactide-co-glycolide and vancomycin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibers onto the surface of vascular prostheses. The in vitro release rates of the pharmaceutical from the nanofiber-loaded prostheses was characterized using an elution method and a high-performance liquid chromatography assay. Experimental results indicated that the drug-eluting prosthetic grafts released high concentrations of vancomycin in vitro (well above the minimum inhibitory concentration) for more than 30 days. In addition, the in vivo release behavior of the drug-eluting grafts implanted in the subcutaneous pocket of rabbits was also documented. The drug-eluting grafts developed in this work have potential applications in assisting the treatment of vascular prosthesis infection and resisting reinfection when an infected graft is to be exchanged.

Extended pain relief achieved by analgesic-eluting biodegradable nanofibers in the Nuss procedure: in vitro and in vivo studies

“…For example, a cisplatin-PLGA nanofiber-coated tracheal stent could deliver the chemotherapeutic agent to the trachea for the treatment of malignant airway obstruction, 20 and a vancomycin-PLGA nanofiber-coated vascular stent could carry the antibiotic to the aortic wall for the treatment of an infected aortic aneurysm. 10,11 In the present study, an analgesic and a local anesthetic were released from the biodegradable PLGA nanofiber system for effective pain relief after surgical implantation of a stainless steel pectus bar. This approach has a great prospect in clinical use for a variety of orthopedic procedures and could potentially reduce the need of postoperative narcotic use, enhance patient satisfaction, and promote early return to normal life after surgery.…”

“…The biodegradable drug-eluting nanofibers were fabricated in our laboratory by using the electrospinning method. 9 The electrospinning setup has been described previously; 10,11 it consists of a 10 mL syringe and needle (internal diameter of 0.42 mm), a ground electrode, a collection plate, and a highvoltage supply. The needle was connected to the high-voltage supply, which generated positive direct current voltages.…”

Management of Vascular Graft Infection

“…For example, vascular grafts with immobilised VEGF and anti-CD34 show improved endothelialisation in vitro and in mice inferior vena cava 15 ; this opens up the possibility of having other factors to modulate the inflammatory reaction to graft insertion, and perhaps locally hinder atherosclerosis. Coating grafts with antibiotics such as vancomycin and rifampicin has been shown to elute high concentrations in vitro and in rabbits in vivo 16,17 . However, it is still uncertain how flow and the surface of the aneurysmal sac will affect the local concentrations of the antibiotic, and what concentration of antibiotic coating is required to provide sufficient time and concentration for infection control.…”

User input in iterative design for prevention product development: leveraging interdisciplinary methods to optimize effectiveness

“…[20–24] Scalability, rate of drug delivery, dissolution and tensile properties (relating to insertion) are grossly tuned by formulation composition (e.g., polymer and solvent choice, drug-polymer combinations), and fiber architecture (achieved by adjusting the electrospinning process). [25–28] Some of these properties have been evaluated in pre-clinical studies:[23, 29, 30] however, like other candidate HIV prevention microbicides, the user perspective has not been incorporated in preclinical development and evaluation. While still a nascent technology for this application, this oversight could risk important preclinical observations toward optimization of drug efficacy and effectiveness.…”