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Development of a Novel Topical Controlled Release System for Otic Drug Delivery

Bruk, Liza (2020) Development of a Novel Topical Controlled Release System for Otic Drug Delivery. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Acute otitis media (OM) is the leading indication for pediatric antibiotic prescriptions, accounting for 25%. While the use of topical ear drops can minimize antibiotic dose and adverse systemic effects compared to oral antibiotics, their use has limitations due to low patient compliance, high dosing frequency, and difficulty of administration. Improper treatment can lead to chronic OM and may require surgical intervention. Previous studies have shown that gel-based otic delivery is possible with invasive intratympanic injection or chemical permeation enhancers which have demonstrated toxicity effects. Further, infection or trauma can cause tympanic membrane (TM) perforation, which can be chronic in up to 46% of cases. Even healing perforations may require months for complete closure, increasing susceptibility to infection, hearing loss, and other side effects. Current treatment standards include surgical grafting, which may result in similar detrimental side effects. Research has accordingly focused on alternative grafts and growth factor or stem cell therapy, which come with logistical and regulatory hurdles.
A novel method of delivering therapeutics to the TM and middle ear was developed using a topical, thermoresponsive gel depot containing antibiotics or stem cell conditioned media (CM)-loaded polymer microspheres. Results indicate that the noninvasive, sustained presentation can allow therapeutically relevant drug concentrations to penetrate the TM to the middle ear for up to 14 days from one topical administration. Auditory brainstem recordings indicate that complete coverage of the TM is achieved and administration can be scaled up if needed. Biocompatibility of all materials is indicated by cytotoxicity testing as well as increased wound healing in CM and CM MS-treated in vitro scratch wound proliferation assays. Despite some variability in the models, in vivo data suggest the system may treat bacterial infection and tympanic membrane perforation, with future studies investigating further scaled up release and longitudinal safety testing. To our knowledge, this dissertation represents the first truly topical drug delivery system to the middle ear for OM with intact TM without the use of CPEs and topical delivery of stem cell secretome to the TM for chronic perforation healing.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Bruk, Lizaliza.a.bruk@gmail.comLAB1540000-0003-1202-1629
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFedorchak, Morganfedorchak@pitt.eduMOD80000-0002-8949-8305
Committee MemberAlper, Cuneytcuneyt.alper@chp.eduCMALPER
Committee MemberMarra, Kaceymarrak@upmc.eduKGM50000-0002-8437-4864
Committee MemberSadagopan, Srivatsunvatsun@pitt.eduVATSUN0000-0002-1116-8728
Date: 29 September 2020
Date Type: Publication
Defense Date: 22 June 2020
Approval Date: 29 September 2020
Submission Date: 7 July 2020
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 170
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: controlled release; topical drug delivery; otic drug delivery; biomaterials; acute otitis media; tympanic membrane perforation
Date Deposited: 29 Sep 2021 05:00
Last Modified: 29 Sep 2021 05:15


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