Desorption-Limited Mechanism of Release from Polymer Nanofibers

Abstract

This work examines the release of a model water-soluble compound from electrospun polymer nanofiber assemblies. Such release attracts attention in relation to biomedical applications, such as controlled drug delivery. It is also important for stem cell attachment and differentiation on biocompatible electrospun nanofiber scaffolds containing growth factors, which have been encapsulated by means of electrospinning. Typically, the release mechanism has been attributed to solid-state diffusion of the encapsulated compound from the fibers into the surrounding aqueous bath. Under this assumption, a 100% release of the encapsulated compound is expected in a certain (long) time. The present work focuses on certain cases where complete release does not happen, which suggests that solid-state diffusion may not be the primary mechanism at play. We show that in such cases the release rate can be explained by desorption of the embedded compound from nanopores in the fibers or from the outer surface of the fibers in contact with the water bath. After release, the water-soluble compound rapidly diffuses in water, whereas the release rate is determined by the limiting desorption stage. A model system of Rhodamine 610 chloride fluorescent dye embedded in electrospun monolithic poly(methylmethacrylate) (PMMA) or poly(caprolactone) (PCL) nanofibers, in nanofibers electrospun from PMMA/PCL blends, or in core-shell PMMA/PCL nanofibers is studied. Both the experimental results and theory point at the above mentioned desorption-related mechanism, and the predicted characteristic time, release rate, and effective diffusion coefficient agree fairly well with the experimental data. A practically important outcome of this surface release mechanism is that only the compound on the fiber and pore surfaces can be released, whereas the material encapsulated in the bulk cannot be freed within the time scales characteristic of the present experiments (days to months). Consequently, in such cases, complete release is impossible. We also demonstrate how the release rate can be manipulated by the polymer content and molecular weight affecting nanoporosity and the desorption enthalpy, as well as by the nanofiber structure (monolithic fibers, fibers from polymer blends, and core-shell fibers). In particular, it is shown that, by manipulating the above parameters, release times from tens of hours to months can be attained.

Current strategies for sustaining drug release from electrospun nanofibers

“…In a separate example, Tiwari et al [68] showed the release of metoclopramide hydrochloride from PVA–PCL (core–shell) fibers exhibited an initial burst to about 55% of the total release. They suggested that the burst effect is most likely due to the presence of pores (either micron or nano-sized) in the PCL shell, which is similar to the release mechanism found by others [69,70]. Therefore, the shell structure and integrity are important to achieve sustained release from core–shell fibers.…”

Monitoring Drug Release from Electrospun Fibers Using an In Situ Fiber-Optic System

“…Conventional dissolution experiments for drug-loaded electrospun fibers are conducted in small vials by immersing a preweighed sample in dissolution medium at physiological pH and temperature. At predetermined time points, defined aliquots are then withdrawn for drug quantification and replaced with fresh dissolution medium (5). However, this dissolution testing procedure is associated with several technical drawbacks.…”

Coaxial Electrospun Poly(methyl methacrylate)–Polyacrylonitrile Nanofibers: Atomic Force Microscopy and Compositional Characterization

“…1–5 Nanoparticles or biomolecules can be encapsulated in the core material with their release controlled by the sheath material properties, which gives rise to core-sheath fiber applications in the drug-delivery field. 6–9 In addition, a synthetic polymer can be used as a structural core support for a biocompatible sheath polymer to improve scaffold mechanical properties for tissue engineering applications. 10–11 …”