Development of Nanostructured Materials for Drug Delivery and Tissue Engineering



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In the last decades many classes of nanoscale materials have been developed to improve the delivery of therapeutics to tissues and cells. The goal of this work was to rationally design and engineer multifunctional nanomaterials with tunable properties to control the release kinetics of therapeutic payloads. The work described herein focuses on the development of materials with nanoscale features that allow them to be environmentally responsive and to sustain the release for long periods of time in a controlled fashion. These materials enhance the pharmacological property of the therapeutics by prolonging their half-life, improving drug solubility and availability, and reducing cytotoxic side effects. All the delivery platforms presented in this work were based on multistage mesoporous silicon nanocarriers (MPS). Firstly, we showed that cefazolin loaded MPS exhibited sustained bactericidal properties. Secondly, we described the surface modification of these particles with natural hydrogel coatings to enhance their ability to extend the release of cargo and preserve its stability. Thirdly, we embedded MPS into a polymeric matrix to provide long-term controlled release of growth factors for tissue engineering applications. Fourthly, we combined all these approaches to engineer a hybrid composite nanomaterial loaded with therapeutic molecules delivered via a bioactive angiogenic hydrogel. This system released all molecules in a sustained and controlled fashion while simultaneously promoting wound healing and neovascularization. Finally, we developed and validated an injectable nanostructured delivery system to provide an extended local anesthetic release for the purpose of surgical analgesia using an incisional model of pain in rodents. We demonstrated the controlled release of anesthetics from a multilayered nanohydrogel and showed the homogeneous diffusion of the drugs at the site of injection. The combination of different nanostructured materials allowed us to build on the individual strengths of each component and resulted in the development of drug delivery system with tunable properties. These nanoscale materials were tested in the context of different clinical domains: infection control, wound healing, pain management and regenerative medicine. The results presented in my work provide the fundamental proof of principle demonstration of the feasibility of these approaches in view of their translation to the clinic.



Nanostructured materials, Drug delivery, Tissue Engineering, Nanomedicine


Portions of this document appear in: Yazdi, Iman K., Matthew B. Murphy, Christopher Loo, Xuewu Liu, Mauro Ferrari, Bradley K. Weiner, and Ennio Tasciotti. "Cefazolin-loaded mesoporous silicon microparticles show sustained bactericidal effect against Staphylococcus aureus." Journal of tissue engineering 5 (2014): 2041731414536573. And in: Murphy, Matthew B., S. M. Khaled, Dongmei Fan, Iman K. Yazdi, Michael Sprintz, Rachel M. Buchanan, Christine A. Smid, Bradley K. Weiner, Mauro Ferrari, and Ennio Tasciotti. "A multifunctional nanostructured platform for localized sustained release of analgesics and antibiotics." European Journal of Pain Supplements 5, no. 2 (2011): 423-432.