Date of Graduation
9-2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Cell & Molecular Biology (PhD)
Degree Level
Graduate
Department
Biological Sciences
Advisor/Mentor
Ryan Tian
Committee Member
Nicholas P Greene
Second Committee Member
Chenguang Fan
Third Committee Member
Kartik Balachandran
Abstract
Nanomaterials have attracted much attention for biomedical applications due to their unique characteristics that are proven to be potential in cell sensing, drug delivery, biological membrane penetration, biocompatibility, and tissue adhesion. The outcomes of this dissertation presented in chapter III-V mainly discuss new approaches in drug delivery, cellular uptake improvement, and neuronal regeneration and protection using a well-optimized titanium-based nanomaterial. In particular, Chapter III summarizes the impact of two different versions of the titanate nanowires on ameliorating the delivery of the antimicrobial and anticancer drug in vitro. Those drugs were loaded on the surface of the fabricated nanowires and characterized using SEM, XRD, and EDX. Our results showed that the thinner and more flexible nanowires (Potassium titanate nanowire) could potentiate the drug therapeutic effect via several mechanisms well discussed in chapter III. On this basis, our investigations were expanded to employee titanate nanowires for the in vivo drug delivery through the blood spinal cord barrier, as detailed in Chapter IV. Therefore, nanowires in suspension were used to deliver a neurotrophic drug (Cerebrolysin) locally and systematically, and the neuroprotection and neuroregeneration effects were tested. Furthermore, titanate nanowires were further modified and optimized for this purpose by developing a titanate implant with titanate nanocarriers etched on the surface of titanium plate for local drug delivery of neurotrophic factor (DL-3-n-butylphthalide) in rats preconditioned with traumatic spinal cord injury. Our findings showed that nanowires significantly facilitate the delivery of the neurotrophic agents through the blood-spinal cord barrier and restore neuronal tissue functionality. To further understand the effect of the nanostructure geometry on the drug delivery process, we synthesized four different titanate nanostructures, including nanowires and nanospheres, and investigated the drug entrapment efficiency, drug loading capacity, and the drug release pattern and behavior using mathematical kinetic modeling of the in vitro drug release data, as discussed in chapter V. The proposed models indicated that the hollow nanospheres followed a Fickian diffusion, while nanowires followed anomalous drug diffusion pattern for drug release. Also, geometrical variations can be carefully optimized during synthesis to satisfy the therapeutic requirement.
Citation
Sahib, S. I. (2023). New Titanate Bioceramic Nanomaterials for Drug Delivery and Controlled Release. Graduate Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/4822