Electronic Theses and Dissertations

Identifier

6320

Date

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Electrical & Computer Engineering

Committee Chair

Bashir I Morshed

Committee Member

Eddie Jacobs

Committee Member

Madhusudhanan Balasubramanian

Committee Member

Warren Haggard

Committee Member

Sanjay R Mishra

Abstract

Direct drug administration has several shortcomings such as low circulation concentration due to rapid flushing by the immune system, non-specificity to target tissue and inefficient delivery to avascular sites. A widely adopted solution to these limitations is to sterically shield the drug from a harsh in vivo environment by encapsulation in a biocompatible, bio-degradable substrate. These Drug Delivery System (DDS) can be localized at the site and release drug gradually until the drug reserve is exhausted. However, the efficiency of this DDS can be further enhanced by designing them to elute drug in response to an external stimulus. This enhancement would enable a healthcare provider to customize therapeutic profiles from the same DDS according to the clinical needs of the patient, without repeated invasive procedures or stronger dosages to maintain potent drug concentration. Our work explored a chitosan based DDS in the form of microbeads which was successfully shown to be responsive to both magnetic and electric stimuli. Chitosan was chosen because it is biodegradable, biocompatible, non-cytotoxic, and has high drug loadability. Magnetic Nanoaparticles (MNP) were added in the chitosan matrix to facilitate stimulus response. Over the course of this research, several cross-linkers like poly-ethylene glycol dimethacrylate (PEGDMA) and glyoxal were tested, and the microbeads loaded with different antibiotics like tetracycline, vancomycin, etc. The current formulation is chitosan/MNP cross-linked with PEGDMA and carrying vancomycin as the drug molecule of interest. The average size distribution of microbeads with this composition was measured at 288.4 ± 62.2 µm, with the embedded MNP sized at 10.89 ± 2.67 nm. A MagneTherm (nanoTherics, UK) was used to provide magnetic stimuli of 25mT at 109.9 kHz to the DDS for 30 mins. Tests conducted in vitro suggested that the DDS was capable of burst-releasing higher amount of drugs on multiple instances of stimuli, separated from each other by several hours (short term study) or even several days (long term study). In a long term study spanning 16 days, magnetic hyperthermia was able to boost vancomycin elution above minimum inhibitory concentration even after 15 days of continuous elution in vitro. It was also observed to be non-responsive to normal temperature elevation (general hyperthermia), indicating that drug elution will not be impacted by in vivo fluctuations in temperature. Our preliminary study using electric stimuli to cause drug delivery was performed with electrodes inside Surface Acoustic Wave (SAW) resonators. The statistically significant drug release compared to non-stimulated samples established DDS sensitivity to electric stimuli and laid the groundwork for designing our custom Inter-Digitated Electrodes (IDEs) with a larger scale on a flexible substrate. We printed IDEs with an Inkjet Materials Printer (DMP 2831, Fujifilm, USA) to apply short bursts of electric pulses of 100 Hz for several seconds to the DDS, and caused a subsequent higher release of vancomycin. These IDEs have an overall dimension of 18.7 mm x 35 mm. The printed electrodes were < 2 µm in height, and were printed by depositing Silver nanoparticle ink (40% loading) on a Polyimide substrate (1 mil thickness). Results demonstrated statistically significant drug release for 3 mins of stimulation. The results showed that both electric and magnetic stimuli can be used to control drug discharge from the chitosan DDS. The platform can be easily customized according to the site of implant and desired dosage profile. The DDS allows multiple stimuli, which can be used independently or in conjunction. The health-provider can choose suitable stimulus to repeatedly administer drug dosage non-invasively when required, leading to enhanced patient recovery and compliance.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.

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