NANOPARTICLE FORMULATIONS TOWARD TREATING AND IMAGING MICROBIAL INFECTIONS

Abstract

Antimicrobial resistance is amongst the greatest medical challenges in modern times. The rise of antimicrobial resistance has drastically reduced, and can potentially eliminate, our ability to treat bacterial infections using drugs. Coordinated action through a variety of disciplines, including those in the medical, regulatory, industrial, and scientific fields is necessary to rise to the challenge. We here present a series of formulation science-based approaches to address resistant infections.

Chapters 1-3 involve enabling the in vivo delivery of next-generation quorum-sensing based drugs. These therapeutics function by disabling pathogens without eliciting a life-death selective pressure, which can potentially be used to treat diseases without spreading resistance. Our work has led to the first examples of quorum-sensing based therapeutics capable of penetrating human in vivo mucus physiological barriers.

Chapters 4-6 detail encapsulating existing antibiotics into vehicles with improved form and function. Antibiotics such as polymyxin B, to which pathogens have not yet widely developed resistance, are reformulated into improved controlled release formations. We also develop a method to surface-modify nanoparticles that bind to bacterial cell walls, towards developing targeted antimicrobial therapeutics. The work here creates new tools that allow for novel use of both old antibiotics and new antibiotic cocktails, that can be used to overwhelm bacterial resistance mechanisms to combat resistant infections. This effort led to the first example of an ion-pairing based, and the first example of a charge-complexation based, approach of encapsulating hydrophilic biologics in a scalable and continuous manner.

While the work above and formulations in general have historically been associated with improving and enabling therapeutics, formulation-guided approaches can also be used for applications beyond therapeutic enhancement. In chapters 7-10, we develop and deliver new imaging agents for applications in medical diagnosis, towards creating rapid and reliable tools for diagnosing resistant infections. This work led to the first example of multiplexed photoacoustic imaging, which can be translated for rapid and real-time diagnosis of multiple pathogens.

Antimicrobial resistance is a complex healthcare problem that requires innovation from all fronts. The work here presents new formulation-based strategies that can be used to treat and image bacterial infections.