Biodegradable Filaments for Controlled Ophthalmic Drug Delivery

Abstract

The focus of this thesis is the wet-spinning, in-vitro characterization, and in-vivo implantation of drug loaded filaments for ophthalmic, controlled-release applications. Filaments of ca. 200-300 micrometers in diameter are comprised of the copolymer poly(d,l-lactide-co-glycolide), with various lactide to glycolide ratios, and either the antibiotic levofloxacin or the steroid dexamethasone. The objective of this work is to develop implantable filaments that can provide long release of drugs in the eye and then dissolve in order to replace eye drops, since poor patient compliance can limit the utility of drops. Filament formation by wet-spinning is examined in Chapter 2. Mass transfer during filament coagulation is experimentally probed. The experimental plan explores the effect of drug on the mass flux of solvent and antisolvent. Drug retention during extrusion is examined in the context of mass transport, as well as solid-state and solution-state thermodynamics. Chapter 3 presents data that show how the composition of the filaments affects the thermal, mechanical, and release properties. By manipulating various aspects of filament formulation (drug content, polymer type, etc.), release rate and mechanical properties can be greatly changed. The development of an in-vivo model (rabbit) to verify in-vitro results is described in Chapter 4. Drug release into the tear film and mechanical stability are determined for one filament using three different implantation techniques. Large exposed sections of filament are necessary for drug release into the tear fluid and filament ends must be secured for in-vivo mechanical stability. In-vivo results correlate well to in-vitro results for both drug release and mechanical life span. A method of combining the properties of different single component filaments through side-by-side multicomponent wet-spinning is described in Chapter 5. Single component properties are maintained by this method, so mechanical and release properties of various monocomponent filaments described in Chapter 3 can be combined into a single filament. This thesis shows that wet-spinning is a versatile method of producing drug loaded filaments with various drug encapsulation and release properties, and that these filaments are well suited for ophthalmic controlled release applications.