Electrospun composite fibers of poly(lactic acid) and halloysite for the sustained co-delivery of drugs with opposite water affinities

Abstract

A dual drug delivery system capable of simultaneous release in a sustained manner a hydrophilic and a hydrophobic drug was prepared, consisting of electrospun poly(lactic acid) (PLA) fibers embedded with halloysite nanotubes (Hal). The hydrophobic drug (dexamethasone, DEX) was directly dissolved in the polymer solution and the hydrophilic drug (gentamicin sulfate, GS) was pre-loaded into Hal. Prior to drug loading, Hal were subjected to an acid treatment to enhance their drug loading capacity. The efficacy of the treatment was confirmed by the increase of the BET surface area and pore volume, determined by nitrogen adsorption/desorption isotherm measurements, and by an increase in GS drug loading (from 18% w/w to 25% w/w), determined by thermogravimetry. Morphologically, the fibers with or without Hal exhibited similar smooth surfaces, with no obvious signs of Hal in the composite fibers, indicating that Hal were well embedded in the fibers. In vitro release tests showed the ability of the composite electrospun fibers to release the two loaded drugs simultaneously in a sustained manner for three weeks, in a biphasic pattern characterized by a burst release in the first 2–3 days followed by a gradual, almost constant release. Furthermore, the antibacterial activity of all GS loaded fibers against Staphylococcus aureus was confirmed by a disc diffusion test. In conclusion, the developed electrospun fibers based on a “nanoparticles in micro/nanofibers” structure proved to be an effective system for the sustained co-delivery of two drugs with opposite water affinities.