Influence of the structure and morphology of ultrathin poly(3-hydroxybutyrate) fibers on the diffusion kinetics and transport of drugs

Ultrathin fibers of a biodegradable polymer poly(3-hydroxybutyrate) with an encapsulated drug (dipyridamole, 0–5% of poly(3-hydroxybutyrate) mass) are obtained by electrospinning. Introduction of the drug substantially affects the geometric shape and crystallinity of individual filaments as well as the total porosity of the fibrillar film on their basis. As follows from the SEM data, in the absence of the drug or at its low concentration (<3%), poly(3-hydroxybutyrate) fibers appear as ellipse-like fragments alternating with cylindrical ones. At a higher content of the drug (3–5%), the abnormal ellipse-like structures are practically absent and the fiber acquires the cylindrical shape. A set of morphological and crystallinity characteristics of the fibers determines the absorption of water and the rate of the diffusion transport of the drug as well as the corresponding profiles of its controlled release. A simplified model of drug desorption from the fibrillar film is advanced which considers two sequential stages of the process: (i) diffusion of the drug in the polymer fiber with coefficient D f ~ 10–12 cm2/s and dimeter φf ~ 2–4 μm and (ii) transport of the drug in the interfibrillar porous space filled by solvent with diffusion coefficient D w = 5.5 × 10–6 cm2/s. Using the characteristics of porosity, crystallinity, and geometry of the fibers and diffusion effective coefficients D eff calculated from the profile of drug release, it is shown that the limiting stage of the transport of the drug is its diffusion in the volume of the cylindrical fiber. The model makes it possible to turn from the experimental values of D eff to partial diffusion coefficients D f and to calculate the kinetic profile of drug release with allowance made for the above-listed factors.