Therapeutic nanofibrous scaffolds in precision drug delivery: formulation design, challenges and regulatory frameworks

INTRODUCTION: Drug-loaded nanofibrous systems represent a breakthrough in drug delivery, overcoming limitations of conventional formulations. They demonstrate controlled morphology and flexibility across multiple administration routes, with versatility delivering small-molecule and biological drugs, and supporting diverse technological implementations. These platforms address unmet clinical needs in dissolution enhancement, drug stabilization, targeted delivery, thus enhancing bioavailability. AREAS COVERED: The expert review critically evaluates formulation design innovations, scalable manufacturing technologies, and application-specific challenges across buccal, nasal, ophthalmic, transdermal, implantable and vaginal nanofibrous systems. It covers the regulatory framework and clinical status while addressing the gap between research and industrial implementation. It emphasizes the critical limitations, drawbacks, and manufacturing barriers that have prevented widespread clinical adoption, alongside strategies to overcome obstacles. EXPERT OPINION: Nanofibrous drug delivery systems offer advantages in dissolution enhancement, biological protection, and patient-tailored administration. However, industrial implementation and regulatory acceptance remain constrained by scalable manufacturing, cost-effectiveness and regulatory harmonization. Despite promising preclinical results, no pharmaceutical drug-loaded nanofiber product has yet achieved FDA or EMA approval.Clinical translation requires process innovation, quality assurance, and demonstrated superiority, supported by artificial intelligence, digital sensors and 3D printing technologies. Over the next five years, nanofiber-based technologies are anticipated to drive innovation in patient-centered therapies.