G.G Wicks, P.M. Weinberger, W.D. Hill
SpheroFill/ Applied Research Center,
United States
Keywords: PWHGMs, nano-porosity, new drug delivery platform, infections, biofilms
Summary:
We present a novel localized drug-delivery platform based on Porous Wall Hollow Glass Microspheres (PWHGMs). These represent a one-of-a-kind material, consisting of tiny hollow glass micro-balloons about 1/3 the diameter of a human hair. Their sizes and properties are controlled for specific applications and are generally within the range of a few to 100 microns in size, with outer shells about 1-2 microns thick. The most unique feature of PWHGMs is a continuous, through-wall shell nano-porosity induced via phase separation and controlled on a scale of 100 to 1,000 Angstroms. The nanopores are formed and oriented so they extend continuously from the outside of the shell to the inside. These openings serve as pathways for loading the PWHGMs with cargos of interest into the relatively large central voids, which can also serve as ‘protective cocoons’ for their contents. The cargo or ‘mixture of cargos’ can consist of antimicrobial agents, be in the form of solids, liquids or even gases, and can consist of a variety of morphologies, including nanoparticles that can subsequently, be released on demand. Additional capabilities of the PWHGM/ cargo systems can also be supplemented by use of coatings, having biocompatible, biodegradable and/or bioactive properties, for a variety of medical diagnostic and treatment applications. PWHGMs were originally developed for nuclear applications at the Savannah River National Laboratory in Aiken, South Carolina. This technology is now being further advanced and tailored for new uses including biomedical applications. Among the interesting applications of PWHGMs and PWHGM composites are uses in Energy, Security, Environmental Remediation and Medicine. Current medical research activities are being conducted by an interdisciplinary team including the Applied Research Center, Medical University of South Carolina and a small biotech start-up company called SpheroFill, LLC. A current focus of the team is on development of PWHGM composites for novel Drug Delivery Systems and in treatment of Fracture Related Infections (FRI) including biofims. Team research involving the PWHGM drug platform has included feasibility studies of incorporation and subsequent release on demand of small-molecule drugs (ex Artemether, used in treating malaria), pentacyclic lactones (ex Ivermectin, a versatile antiparasitic drug) and fluoroquinolone antibiotics (ex Ciprofloxacin, important in treating infections). Additional work related to the infection research will also include prevention and disruption of biofilms. Promising biofilm disruption strategies that have been developed, including matrix-degrading enzymes (ex DNases, dispersion B), antimicrobial peptides, nitric oxide donors, and nanoparticles targeting biofilm integrity, that have acknowledged critical delivery barriers. PWHGMs have the potential to enable localized, protected, sustained, delivery of mixed sets of these small molecules, biological agents and very uniquely, gases (ex NO, O2) directly within infection sites to inhibit or disrupt resistant microbial communities.