pH-responsive biomaterials for smart intravaginal drug delivery
| dc.contributor.author | Kim, Seungil | |
| dc.contributor.examiningcommittee | O'Neil, Joe (Chemistry) Ko, Ji Hyun (Human Anatomy and Cell Science) Narain, Ravin (Chemical and Materials Engineering, University of Alberta) | en_US |
| dc.contributor.supervisor | Liu, Song (Biosystems Engineering) | en_US |
| dc.date.accessioned | 2018-08-17T17:52:35Z | |
| dc.date.available | 2018-08-17T17:52:35Z | |
| dc.date.issued | 2018 | en_US |
| dc.date.submitted | 2018-07-24T14:35:57Z | en |
| dc.degree.discipline | Biomedical Engineering | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | For better combating human immunodeficiency virus (HIV), pH-triggered on-demand intravaginal release of anti-HIV drugs or nanocarrier was proposed to avoid unnecessary exposure to drug and reduce side effects. Because normal human vaginal tract pH is acidic (3.5-4.5) and can be elevated to neutral by the introduction of seminal fluid during heterosexul intercourse. To acheve the goal, new pH-responsive polyurethanes (PUs) were synthesized from polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), methylene di-p-phenyl diisocyanate (MDI), 1,4-bis(2-hydroxyethyl)piperazine (HEP), dimethylolpropionic acid (DMPA), and propylene glycol (PG) for the fabrication of intravaginal biomaterials. Solvent-cast PEG-HEP-HDI-PG and PEG-HEP-MDI-PG membranes were fabricated and showed pH-triggered reversible changes in swelling ratio and surface morphology. The solvent-cast membranes demonstrated pH-responsive switchable on-and-off release of sodium diclofenac (NaDF): triggered release at pH 7.0 (˃ 10%) but little-to-no release at pH 4.2. Electrospun PEG-HEP-MDI-PG membrane was fabricated for the controlled release of nanocarriers since the solvent-cast PU membranes don’t have sufficient interconnected pores to allow traverse of nanoparticles (NPs). The electrospun membrane demonstrated almost no release of VisiblexTM color dyed polystyrene nanoparticles (PSNs, 200 nm, -COOH) at pH 4.5 (2 ± 1.3%) but a continuous release at pH 7.0 (60 ± 6.2%) for 24 h. These pH-responsive PU membranes were developed as a “window” membrane of reservoir-intravaginal ring (IVR) for the on-demand release of drugs or nanocarriers. The PU membranes did not show noticeable negative impact on viability of VK2/E6E7 human epithelial cells and Sup-T1 human T-cells or induction of pro-inflammatory cytokines (interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1 beta (IL-1)) production. At last, the pH-triggered switchable release of nanocarriers was achieved by fabricated PEG-DMPA-HDI-PG hydrogel (20 wt% in distilled water). The fluorescent dye, orange II, labeled PEGylated poly(aspartic acid)-based NP (251-283 nm) was synthesized for release study and blended with PU hydrogel to form a supramolecular complex hydrogel. Then the complex hydrogel was filled into the lumen of segmented reservoir-IVRs containing two holes. In vitro release study showed close-to-zero release of NPs at pH 4.2, and then 18.5 ± 5.2% release of NPs for the next 1 h at pH 7.0, followed by the switchable on-and-off release for 5 h. | en_US |
| dc.description.note | October 2018 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/33210 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Smart drug delivery, Anti-HIV, pH-responsive polyurethanes, Intravaginal Biomaterials, Controlled release of nanoparticles | en_US |
| dc.title | pH-responsive biomaterials for smart intravaginal drug delivery | en_US |
| dc.type | doctoral thesis | en_US |