One of the most common methods of drug delivery to the anterior segment of the eye is topical application of an ophthalmic solution or suspension. The ophthalmic solution may contain various particle based materials, such as nanoparticles, to control the rate at which the drug is delivered to the eye. The issue with this delivery method is that there are several barriers at the front of the eye. These barriers, which include a high tear film turnover rate and induced lacrimation, reduce the residence time of the drug at the site of administration and result in 95% of the administered drug being removed systemically or via nasolacrimal drainage. Additionally, once the material has left the target location it should degrade in a controlled manner so that it can be safely removed from the body.
The current work focuses on the development of polymeric nanoparticles that can serve as a delivery system for ophthalmic drugs. The material proposed for the nanoparticle synthesis is poly(2-hydroxyethyl methacrylate (HEMA)), a polymer with a long history of ophthalmic compatibility. The original nanoparticle formulation was modified to allow for degradation and mucoadhesion. To facilitate degradation, a crosslinker which degrades under ocular conditions was incorporated. A mucoadhesive polymer was incorporated into the particles to enhance the residence time of the particles at the front of the eye.
Size and morphology analysis of the final polymer products showed that nano-sized, spherical particles were produced. FTIR spectra demonstrated that the nanoparticles were comprised of poly(HEMA) and that 3-(acrylamido)phenylboronic acid (3AAPBA) was successfully incorporated. Degradation of nanoparticles containing N,N’-bis(acryloyl)cystamine (BAC) after incubation with DL-dithiothreitol (DTT) was confirmed by a decrease in turbidity, measured by absorbance, and through transmission electron microscopy (TEM). Based on zeta potential results, poly(HEMA, BAC, 3AAPBA) samples C3 to C6 were found to be mucoadhesive. Dexamethasone release from poly(HEMA) nanoparticles and poly(HEMA, BAC, 3AAPBA) nanoparticles, loaded with efficiencies of 15.0% ±1.4% and 5.3% ±0.4%, resulted in rate constants of 0.001 and 0.002, and release exponents of 0.607 and 0.586, respectively. The toxicity of the nanoparticles was tested by incubation in the presence of human corneal epithelial cells (HCEC). In the presence of the poly(HEMA), poly(HEMA, BAC), and poly(HEMA, BAC, 3AAPBA) samples the HCEC viability was found to be 123.6% to 182.5%, 88.5% to 111%, and 69.8% to 85.1%, respectively. The viability of HCEC after incubation with poly(HEMA) was significantly higher compared to poly(HEMA, BAC) samples with a dilution factor of 0 and 2. Additionally, the HCEC viability in the presence of poly(HEMA, BAC, 3AAPBA) sample C6 was found to be significantly lower compared to samples C2 and C3 from Table 3. The previously summarized results suggest that the poly(HEMA) based nanoparticles produced in this work have the potential for drug delivery to the front of the eye. / Thesis / Master of Applied Science (MASc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/20426 |
| Date | January 2016 |
| Creators | Mangiacotte, Nicole |
| Contributors | Sheardown, Heather, Chemical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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