Abstract
(type = abstract)
Novel, controlled release drug delivery systems have transformed therapeutics used in modern medicine but exhibit limitations for treating various diseases. Biodegradable polymers have been extensively studied to overcome such challenges. Through incorporating therapeutic bioactives into a polymer backbone via hydrolytically degradable bonds, high drug loading, improved delivery, and enhanced bioactive stability can be achieved. Polymers containing a non-steroidal anti-inflammatory drug, salicylic acid, and antioxidant molecules from the hydroxycinnamic acid class were synthesized into bioactive-based poly(anhydride-esters) as controlled release drug delivery systems. Polymer properties have been tuned by changing the bioactive covalently incorporated into the monomer unit, altering the monomer’s molecular structure, adding small molecules to the polymer matrix, and fabricating the polymer into different devices. Salicylic acid-based poly(anhydride-ester) (SAPAE) release profiles were first tuned using small molecule admixtures at varying weight percentages to overcome a lag period (i.e., no drug release) for applications where immediate, constant drug release is desired. SAPAEs were also designed as microparticles, or microspheres, for short-term salicylic acid release. These polymers were prepared using monomers comprised of linear aliphatic or heteroatomic molecules with two salicylic acid units. Microsphere size and morphology was determined and the in vitro drug release profile ascertained. Furthermore, to impart brittle SAPAEs with flexible, soft tissue-like properties, the polymer was blended with poly(vinyl pyrrolidone) to formulate miscible films that, when hydrated, exhibit hydrogel-like properties. The material’s morphology, thermal properties, and in vitro drug release profile were elucidated. In addition to engineering SAPAEs for various applications, hydroxycinnamic acids such as p-coumaric, ferulic, and sinapic, which are potent antioxidants with short half-lives and poor chemical stability, were covalently incorporated into a polymer backbone. The chemical composition of precursors and polymers were confirmed and the polymers’ physicochemical characteristics and drug release profiles ascertained. Moreover, the ferulic acid-containing polymer chemical structure was tuned to alter the physicochemical properties and drug release rates. The design, synthesis, physicochemical characterization, drug release profiles, bioactivity assessments, device fabrication methods, biocompatibility evaluations, and potential applications of various bioactive-containing poly(anhydride-ester) are discussed herein.