Document Type

Dissertation

Date of Award

2022

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

Daniel Engebretson

Abstract

Intracranial atherosclerotic disease (ICAD) remains a leading cause of ischemic events such as stroke. However, the use of drug coated balloons (DCBs) containing paclitaxel (PAT) in the brain vasculature remains limited. This is the result of several factors including particulate shed from polymer excipients, PAT toxicity, and poor blood-brain barrier (BBB) permeability of PAT. Therefore, there is a need for novel PAT and excipient formulations for balloon coatings to improve delivery of PAT to the arterial wall in ICAD while reducing off target drug effects and particulate shed. GM1 has previously been shown to cross the BBB and have high specificity for the brain. GM1 can also be incorporated into liposomes for use as a drug delivery vehicle. Therefore, specific aim-1 in this dissertation was to prepare liposomes incorporating GM1 for use as a drug delivery vehicle for PAT. The resulting DOPC/GM1 liposomes were around 120 nm in size with a high degree of uniformity and stability. The loading of PAT into the DOPC/GM1 liposomes also resulted in a high encapsulation efficiency. Specific-aim 2 was to assess the if the presence of GM1 in DOPC liposomes improves the transport of PAT across an in vitro BBB. The presence of 0.5 mol % of GM1 in DOPC liposomes did not improve the transport of PAT across the in vitro BBB, with the amount of PAT bypassing the hCMEC/d3 cells being similar to the control. Therefore, higher concentrations of GM1 in DOPC liposomes were assessed. Neither 2 mol % nor 5 mol % GM1 in DOPC liposomes improved the transport of PAT across the BBB. Specific-aim 3 was to incorporate DOPC/GM1 liposomes into PEO thin films for future use as a balloon coating. SEM demonstrated that the liposomes are dispersed within the PEO. The ability of PEO to interact with the liposomes for controlled release was also assessed by dissolving PEO only and PEO + liposome films and comparing the time to dissolve. The addition of liposomes did not affect the time to dissolve, suggesting that additional functional groups are needed in the liposomes to sufficiently interact with PEO for controlled release.

Subject Categories

Biomedical Engineering and Bioengineering

Keywords

Intracranial atherosclerotic disease (ICAD)

Number of Pages

103

Publisher

University of South Dakota

Share

COinS