SAKHARKAR, MRUNAL K.
(2019)
DEVELOPMENT OF MICRO-PATTERNED FILMS FOR OPHTHALMIC DRUG DELIVERY.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Ocular inflammation is commonly associated with multiple eye disorders such as microbial infections, allergies and post-operative healing. Topical anti-inflammatory agents delivered via eye drops or ointments are commonly used for the management of inflammation. These treatment regimens involve high dosing frequency over prolonged periods depending on the severity of inflammation. Further, only 5% of administered drug may be available for action due to the physiological barriers of the eye and formulation losses. Collectively, this reduces patient compliance and causes irregularity in drug exposure. Therefore, there is a need for prolonged residence time of formulation in the eye to achieve sustained drug delivery. Mucoadhesive polymers and ocular inserts have been used for this purpose. Additionally, topographical features have been explored to enhance adhesion to mucosal surfaces. Taking inspiration from these approaches, we hypothesized that micropatterned polymeric films will prolong residence time by enhancing interactions with ocular mucosal surface and sustain the drug release.
We developed micropatterned films containing a hydrophobic drug, hydrocortisone (HCT) or a hydrophilic drug, olopatadine hydrochloride (OLO) using GRAS-compliant cellulose-based polymers and polylactic-co-glycolic acid (PLGA). Films with 100 µm sized square, triangle and circle micropatterns were manufactured and characterized for HCT / OLO release. We demonstrated an in vitro sustained release for up to 72 hours, for both HCT and OLO. The shape of micropatterns did not impact drug release, however, PLGA and hydroxyethylcellulose impacted release of HCT and OLO, respectively. Tensile properties of films were dependent on the film composition and not micropatterns. A novel method to investigate the mucoadhesion potential of micropatterned films was developed. For cellulose and PLGA-based films, micropatterns did not improve adhesion to porcine intestinal tissue. Collectively, our results suggest that sustained release of anti-inflammatory drugs can be achieved by using cellulose and PLGA-based films and the presence of 100 µm sized micropatterns did not improve adhesion to mucosal surface. Further optimization of formulation and micropattern characteristics will be required to maximize sustained release and mucoadhesion in films, which can potentially be used for long-term delivery to the anterior region of the eye.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
5 April 2019 |
| Date Type: |
Publication |
| Defense Date: |
27 March 2019 |
| Approval Date: |
5 April 2019 |
| Submission Date: |
4 April 2019 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
84 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Micropatterns, polymeric films, hydrocortisone, olopatadine hydrochloride, HPMC, HEC, HPC, PLGA, mucoadhesion |
| Date Deposited: |
05 Apr 2019 16:21 |
| Last Modified: |
05 Apr 2021 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/36288 |
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