OpenNano · Published 2026-06-29 · DOI 10.1016/j.onano.2026.100312
Alireza Maboudi, Mahdi Soltanoghli, Mohammadmahdi Ghavamipour Komleh
Electrospun nanofibers function not simply as release matrices, but as structural determinants of route-specific pharmacokinetic input and exposure. This review analyzes how nanofiber architecture, polymer composition, and drug-matrix interactions reshape route-specific pharmacokinetic behavior. Mechanistically, nanofibers influence pharmacokinetics by modifying dissolution rate, stabilizing amorphous drug states, regulating input functions, enhancing barrier interaction, and enabling localized depot formation. These effects translate into measurable pharmacokinetic outcomes, reduced fluctuation index, and decoupling of local tissue exposure from plasma concentrations.Mapping mechanistic design variables to dominant biological bottlenecks reveals that pharmacokinetic performance is fundamentally route-dependent. While oral systems frequently enhance systemic exposure through dissolution-driven absorption, mucosal and implantable nanofibers more commonly engineer spatially controlled local exposure with limited systemic spillover. Current in vivo evidence supports these route-specific pharmacokinetic advantages but remains heterogeneous, with limited systematic pharmacokinetic evaluation, weak in vitro-in vivo correlation, and minimal integration of physiologically based pharmacokinetic (PBPK) and pharmacokinetic-pharmacodynamic (PK-PD) modeling.This review introduces a route-aware pharmacokinetic design framework that integrates nanofiber architecture, biological bottlenecks, and graded levels of PK evidence to guide rational exposure engineering. The paper should be read as a mechanistic framework for organizing current evidence, rather than as a systematically conducted evidence synthesis. By positioning electrospun nanofibers as pharmacokinetic input-function shaping systems, this review proposes a route-aware design and evidence framework to guide rational development and translational assessment of nanofiber-mediated drug exposure.
Abstract from DOAJ. Public domain (CC0 1.0).
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Maboudi, A., Soltanoghli, M., Komleh, M. (2026). Electrospun nanofibers for route-specific pharmacokinetic modulation: Mechanistic insights, evidence gaps, and translational challenges. OpenNano. https://doi.org/10.1016/j.onano.2026.100312