Advanced electrospun nanofibrous architectures for multidrug delivery systems

Complex diseases such as chronic wounds, cancer, infections, and degenerative disorders often cannot be adequately treated with a single drug. Therefore, multi-drug combination therapy has become a proven method for overcoming treatment resistance and improving patient outcomes. In this regard, electrospinning offers a versatile platform for delivering multiple drugs by allowing precise control over fiber shape, compartment structure, and the spatial distribution of drug payloads within a single fibrous material. In this review, we discuss recent progress in advanced electrospun structures designed for multi-drug combination therapy, with particular emphasis on how structure influences drug release behaviour. Bilayer and multilayer structures enable programmed and sustained drug release, whereas core-shell architectures created through coaxial and multiaxial electrospinning provide synchronized delivery and reduce initial burst release. Janus and side-by-side fiber architectures represent emerging platforms that enable spatially distinct and parallel co-delivery of incompatible therapeutic agents. We further consider the interplay between polymer choice, drug loading, and release kinetics. Finally, we address key limitations and translational challenges-such as scalability, lab-to-clinic differences, solvent safety, and regulatory issues-to guide the design of next-generation electrospun platforms for combination therapy.