Micro-modulation of the intra-structural environment in electrospun drug delivery systems: effects on drug release and hydrolytic degradation.

Poor aqueous solubility can limit drug release from biodegradable implants. We developed a multifunctional dual-jet electrospun drug-delivery system (DDS) designed to accelerate the release of poorly water-soluble bioactive substances. Its principle is based on introducing the drug-carrying matrix and release-rate modifier as separate, interlaced fractions. Poly(D,L-lactide-co-glycolide) (PDLGA) nonwovens or poly(ε-caprolactone-co-trimethylene carbonate) (PCLTMC) membranes served as sirolimus carriers, whereas poly(vinyl alcohol) nanofibres loaded with lactic acid (PVA(LA)) were designed to increase incubation-medium accessibility, lower the pH of the aqueous environment and catalyse early-stage matrix hydrolysis. Both copolymers had defined chain microstructures with relatively short comonomer sequences, intended to limit changes in physical properties and molar composition during incubation. Drug release and early-stage hydrolytic degradation were evaluated over 28 days in deionised water and phosphate-buffered saline. Dissolution of the PVA(LA) fraction increased incubation-medium uptake and was associated with accelerated sirolimus release in water. After 28 days, cumulative release increased from 12.76 to 29.32% for PDLGA and from 22.03 to 59.03% for PCLTMC. LA release reduced bulk-medium pH to 3.14-3.21 after one day. Modest hydrolytic changes were detected for PDLGA, whereas the effect on PCLTMC was limited. Both carriers remained amorphous, showed only small changes in glass-transition temperature (Tg) and retained stable molar compositions. Release was diffusion-dominated, with possible contributions from medium uptake and structural reorganisation. This approach integrates a biodegradable drug carrier with an interlaced, dissolving modifier fraction, allowing the release environment to be modified and drug release to be accelerated without altering the chemical composition of the matrix.