Polycaprolactone Hollow Fiber Membranes for Sustained Bevacizumab Release

Abstract Hollow fiber membranes (HFMs) are hollow, cylindrical membranes commonly used for filtration. In this study, polycaprolactone (PCL), a biodegradable polymer, was used to fabricate HFM implants for sustained drug delivery. Monoclonal antibodies (mAbs), including bevacizumab, are used in the treatment of neovascular age-related macular degeneration (AMD), and sustained delivery systems may reduce the need for repeated intravitreal injections. This study investigated how varying the bore-to-dope fluid flow ratio and PCL concentration during dry-wet jet spinning affects HFM geometry, internal morphology, and bevacizumab release kinetics. Increasing the flow ratio resulted in larger HFM diameters and thinner membrane walls, while porosity and void fraction remained relatively unchanged. In contrast, increasing the PCL concentration from 15 wt % to 21 wt % altered the internal membrane morphology, reducing macrovoid formation and increasing the sponge-like region. These morphological changes were associated with slower and more prolonged bevacizumab release, demonstrating that release behavior can be modulated through HFM morphology. To further investigate the relationship between membrane microstructure and drug transport, SEM cross-sectional images were analyzed to obtain pore structure statistics and generate stochastic three-dimensional membrane domains for kinetic Monte Carlo (kMC) simulations. Using molecular diffusivity estimated from the Stokes–Einstein relationship, the microstructure-informed model predicted bevacizumab transport and release profiles that were consistent with the experimental release behavior. The 21 wt % PCL HFMs demonstrated sustained bevacizumab release for 57 days. Collectively, these findings establish relationships among HFM fabrication conditions, membrane morphology, and macromolecular transport and provide a basis for further development of biodegradable HFM systems for sustained delivery of therapeutic antibodies.