Factors Controlling Drug Release in Cross-linked Poly(valerolactone) Based Matrices

There is keen interest in the development of biocompatible and biodegradable implantable delivery systems (IDDS) that provide sustained drug release for prolonged periods in humans. These systems have the potential to enhance therapeutic outcomes, reduce systemic toxicity, and improve patient compliance. Herein, we report the preparation and physicochemical characterization of cross-linked polymeric matrices from poly(valerolactone)-co-poly(allyl-delta-valerolactone) (PVL-co-PAVL) copolymers for use in drug delivery. A series of well-defined PVL-co-PAVL copolymers (PDI < 1.5) that vary in terms of MW and AVL content were prepared by ring opening polymerization catalyzed by 1,5,7-triazabicydo[4.4.0]dec-5-ene. A subsequent cross-linking reaction using 1,6-hexanedithiol led to solid cylindrical amorphous or semicrystalline matrices as potential IDDS. High loading levels (up to 20% (w/w)) of several model drugs that vary in physicochemical properties, including paditaxel, triamcinolone acetonide and hexacetonide, curcumin, and acetaminophen, were achieved using a postloading method in organic solvent. Drug IDDS interactions were evaluated via the group contribution method and X-ray diffraction as well as calorimetric, spectroscopic, and microscopic techniques. Results indicate superior drug matrix compatibility for drugs bearing phenyl groups. In vitro release studies under distinct sink conditions highlight the key factors (i.e., state and loading level of drug, solubility of drug in external media, and composition of release media) that impact drug release.