Memoli, Kevin A.. Polymers for the sustained and localized release of anti-inflammatory and anti-cancer drugs. Retrieved from https://doi.org/doi:10.7282/T3930RZK
DescriptionThe practical utility of chemically incorporating drugs into polymers for the localized and sustained delivery of such drugs has been well established. Sustained release provides therapeutic concentrations of drug over a long time period, obviating the need for frequent dosing, leading to better patient compliance and mitigating the likelihood of overdosing. Localized delivery mitigates the severity of side effects associated with systemic administration and increases efficacy by increasing the effective dosage at the site of the pathology. In this thesis, these principles have been investigated for the delivery of anti-inflammatory and anti-cancer drugs. Amfenac, a non-steroidal anti-inflammatory drug (NSAID), in the form of its prodrug nepafenac, has been proven to be effective for the treatment of anterior uveitis (i.e. ocular inflammation) via topical administration of an aqueous suspension, but posterior uveitis is difficult to treat in this manner as drug penetration to the rear of the eye is inefficient and clearance is very rapid, limiting the practicality of administration by injection. The objective was to chemically incorporate amfenac into a biodegradable polymer that can be fabricated into microspheres suitable for injection into the rear of the eye for the sustained release of amfenac to treat posterior uveitis. This polymer consists of a poly(amide-imine) derived from an analog of nepafenac. Herein is described the polymer synthesis and the preparation and degradation of PolyAspirinTM microspheres incorporating sodium amfenac. Nutlin is a member of an anti-cancer drug family developed by Hoffmann-LaRoche, Inc. The objective of this project was to attach a nutlin analog to a biodegradable polymer backbone and fabricate the resulting polymer into wafers that could be surgically implanted to treat brain cancer. Described herein are efforts to incorporate a nutlin analog into a polymer backbone based on pyromellitic acid.