Multiple hour antifibrotic drug release enabled by a thermosensitive quadpolymer.

Injectable drug delivery for uterine fibroid therapy is an ambitious, possibly fertility-preserving concept, that could meet the challenges associated with the structure of these tumors and their location in the uterus. This study was conducted to advance a thermosensitive injectable quadpolymer for effective sustained release of anti-fibrotic drug formulations and to evaluate the feasibility of its use for delivery of the anti-fibrotic drug pirfenidone as a therapy to reduce fibroid cell proliferation. A series of quadpolymers were prepared by free radical polymerization of N-isopropylacrylamide (NIPAM) with different amounts of polylactic acid functionalized hydroxyethyl methacrylate (HEMA-PLA), acrylic acid (AAc), and methacrylate functionalized hyperbranched polyglycerol (HPG-MA) to optimize the sol-gel phase transition temperature and mechanical stiffness. Poly(NIPAM-co-HEMA-PLA-co-AAc-co-HPG-MA) with feed ratio (83-7-1-9), at 17% w/v, readily formed an aqueous solution that could be manipulated by syringe at room temperature. The quadpolymer also rapidly formed a stable gel at physiological body temperature, and partially biodegraded over time as confirmed by several spectroscopic characterization techniques. To evaluate the potential range of utility, quadpolymer 83-7-1-9 was loaded in-vitro with caffeine (a prototype hydrophilic drug) or the hydrophobic drug pirfenidone. Pirfenidone-loaded quadpolymer 83-7-1-9 formulations released 50% of drug loaded in double the time as compared to other reported liposome and nanoparticle injectable pirfenidone formulations. Furthermore, treatment of cultured fibroid cells with pirfenidone-loaded quadpolymer 83-7-1-9 formulations confirmed that activity of pirfenidone was preserved and proliferation of fibroid cells was inhibited. These results support that quadpolymer 83-7-1-9 is a promising candidate to be further developed for localized delivery of drugs for uterine fibroid therapy.

Duke Scholars

Author Friederike Luking Jayes Obstetrics and Gynecology, Reproductive Sciences

Author Darlene Kimber Taylor Obstetrics and Gynecology