Controlled Delivery of Antibiotics with Nanocarriers and Thin Films

Abstract

Antibiotic resistance is a significant global problem that contributes to $20 billion in healthcare costs, $35 billion in societal costs, and 8 million days of hospitalization per year. Current administration of antibiotics is non-specific, non-targeted, and non-localized, and delivering antibiotics in nanoparticles can help overcome these weaknesses. The development of economical and scalable antibiotic nanoparticle encapsulation processes can help the translation of antibiotic-nanoparticle therapies. Flash NanoPrecipitation (FNP) is a method capable of producing large quantities of nanoparticles with encapsulated drug and can be a scalable, economical solution to the problem of antibiotic encapsulation. In our work, we developed formulations for successfully encapsulating both hydrophilic and hydrophobic antibiotics (totarol, rifampicin, erythromycin, azithromycin, and tobramycin) in nanoparticles and characterized nanoparticle stability. Biological assays with two of the antibiotic nanoparticles (totarol and azithromycin) demonstrated high antibacterial activity against S. aureus. Infections in medical devices such as catheters are also a major health issue, with an annual cost of managing infections for catheters estimated between $296 million and $2.3 billion. We developed and tested a cheap, scalable “flushing” method of antibiotic and block copolymer deposition on the interior of catheters. Of the six materials tested with Nile Red, a hydrophobic drug analogue, silicone was the most promising material for thin film coating. Deposition tests with totarol demonstrated that significant amounts of totarol could be deposited on both silicone and polyethylene. These materials were found to be both biologically active and resistant to bacterial absorption. These initial tests demonstrate that the flushing methodology is promising as a technique to deposit antibiotic and block copolymer on catheter tubing.