On-Demand and Long-Term Drug Delivery from Degradable Nanocapsules

Abstract

While there are a number of nanomaterials that can lead to on demand drug delivery or longterm delivery, there are limited nanotechnologies that are stable for long times, deliver sustained amounts of drugs, and achieve repeated, on demand delivery. We have developed a system based on polyurethane nanocapsules as a platform for long-term and on demand delivery. We synthesized nanocapsules encapsulating either a model drug, fluorescein, or a clinically relevant drug, acriflavine, a HIF-1alpha inhibitor. The nanocapsules were ~250 nm in diameter as measured by DLS and confirmed via SEM, and the molecules were localized in the walls of the nanocapsules as determined by confocal microscopy. Release studies were performed at 37 C in PBS, and both the fluorescein and acriflavine were delivered over several weeks. At the end of the release, no pellet was detectable upon centrifugation of the nanocapsules confirming degradation of the polyurethane shells. The same particles released a fraction of their payload upon the application of either an ultrasonic probe or a clinical grade, ultrasound imaging system used for assessing the retina. The amount of drug released could be tailored by the energy applied to the nanocapsules. One of the most exciting findings beyond being able to tailor how much was released based on the energy applied and the time it was applied was that these nanocapsules could be triggered to release multiple times with at least 10 separate release events triggered for each formulation. Being able to tailor the on-demand release over multiple cycles has the potential to fundamentally change how we can approach delivery of drugs for a variety of applications.

Getting to the Core of It All: Nanocapsules to Mitigate Infusion Reactions Can Promote Hemostasis and Be a Platform for Intravenous Therapies

“…The nanocapsules' dynamic light scattering (DLS) data show that the nanocapsules are ∼150−250 nm in size, and the zetapotential changes are based on the surface composition (Figure 2B). As previously observed, 24 the nanocapsules in DLS display two peaks with most nanocapsules in the 150−250 nm size range. A very small population of nanocapsules <10 nm was observed.…”

“…Polyurethane nanocapsules are likely to be valuable, however, for ultrasound imaging and drug delivery. 24 Polyurethane nanocapsules open new possibilities for treating trauma safely. Having a system that does not activate complement or trigger cytokine responses but promotes rapid hemostasis is critical to move the field of infusible nanotechnologies forward.…”

“…Polyurethane nanocapsules have drawn interest for a range of applications in the biomedical field. Urethane linkages can be cleaved chemically or enzymatically with enzymatic cleavage being the most common pathway in vivo. , We have previously used polyurethane nanocapsules as a drug delivery system . In the current study, we endeavored to determine how these nanocapsules compared to our previous polyester-based nanomaterials regarding complement activation and whether they might have potential as a hemostatic system.…”

“…We prepared polyurethane nanocapsules and PEGylated polyurethane nanocapsules through interfacial polymerization by modifying a previously published protocol (Supporting Information Figure 1). , To functionalize the nanocapsules, we used NHS/EDC-based bioconjugation technique to conjugate the carboxyl end group of the exposed PEG on the nanosurface with the primary amine group of the peptide motif GRGDS.…”

“…The good news is that polyurethane cores are unlikely to be unique in eliciting no measurable complement response. Polyurethane nanocapsules are likely to be valuable, however, for ultrasound imaging and drug delivery …”