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.
The U.S. Agency for Healthcare Research and Quality estimates that there are over 1 million total hip and total knee replacements each year in the U.S. alone. Twenty five percent of those implants will experience aseptic loosening, and bone cement failure is an important part of this. Bone cements are based on poly(methyl methacrylate) (PMMA) systems that are strong but brittle polymers. PMMA-based materials are also essential to modern dental fillings, and likewise, the failure rates are high with lifetimes of 3-10 years. These brittle polymers are an obvious target for self-healing systems which could reduce revision surgeries and visits to dentist. Self-healing polymers have been described in the literature since 1996 and examples from Roman times are known, but their application in medicine has been challenging. This review looks at the development of self-healing biomaterials for these applications and the challenges that lie between development and the clinic. Many of the most promising formulations involve introducing nanoscale components which offer substantial potential benefits over their microscale counterparts especially in composite systems. There is substantial promise for translation, but issues with toxicity, robustness, and reproducibility of these materials in the complex environment of the body must be addressed.
Bone cements and dental resins are methacrylate-based materials that have been in use for many years, but their failure rates are quite high with essentially all dental resins failing within 10 years and 25% of all prosthetic implants will undergo aseptic loosening. There are significant healthcare costs and impacts on quality of life of patients. Self-healing bone cements and resins could improve the lifespan of these systems, reduce costs, and improve patient outcomes, but they have been limited by efficacy and toxicity of the components. To address these issues, we developed a self-healing system based on a dual nanocapsule system. Two nanocapsules were synthesized, one containing an initiator and one encapsulating a monomer, both in polyurethane shells. The monomer used was triethylene glycol dimethacrylate. The initiator capsules synthesized contained benzoyl peroxide and butylated hydroxytoluene. Resins containing the nanocapsules were tested in tension until failure, and the fractured surfaces were placed together. 33% of the samples showed self-healing behaviors to the point where they could be reloaded and tested in tension. Furthermore, the capsules and their components showed good biocompatibility with Caco-2 cells, a human epithelial cell line suggesting that they would be well tolerated in vivo.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.