Electrospun nanofibrous membranes have emerged as a promising tool for controlled release of various therapeutic agents. While a zero-order release kinetic is desired for many applications, nanofibrous membranes mostly demonstrate a burst release followed by a gradual release of their payload. This research was performed to develop and characterize electrospun composite nanofibrous membranes, made of polycaprolactone (PCL) and chitosan (CS), for sustained release of azithromycin from electrospun PCL fibers with minimized burst release. Compared to PCL nanofibrous membrane, PCL/CS nanofibrous membranes showed a similar fiber diameter, higher ultimate tensile strain and tensile strength, lower pore diameter, lower water contact angle, and higher water uptake. In vitro drug release analysis for 25 days revealed that drug release from composite electrospun PCL/CS membranes is controlled by different mechanisms at different time periods. During the first few days, drug release is controlled by the desorption mechanism of drug molecules present over the surface of nanofibers and also the diffusion of some drug molecules close to the surfaces of nanofibers. After this phase, swelling of CS nanofibers reduces the pore size of the membrane, which results in slower drug diffusion with a subsequent decreased release rate. As time goes on, drug release is mainly affected by the degradation of CS fibers that results in the transport of remaining drugs through the created pores within degraded CS nanofibers. The amount of cumulative drug release from PCL/CS composite membranes was about two times more than that from PCL membranes. It was also observed that the percentage of PCL integration directly affects the amount of drug release. It confirms that release rate and the amount of released drug could be tailored by adjusting the material composition and modulating morphological features such as fiber diameter.

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