Date of Graduation

12-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Cell & Molecular Biology (PhD)

Degree Level

Graduate

Department

Cell & Molecular Biology

Advisor/Mentor

Tian, Z. Ryan

Committee Member

Greene, Nicholas P.

Second Committee Member

Fan, Chenguang

Third Committee Member

Balachandran, Kartik

Keywords

Nanomaterials; Drug delivery; Cellular uptake; Neuronal regeneration; Cerebrolysin

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.

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