Systemic toxicity is an obstacle against the oral administration of colchicine. The high body surface area to mass ratio in pediatrics would dramatically enhance the toxicity risk. This issue could be jettisoned by formulation of an optimized nanofiber-based fast dissolving delivery system. It could enhance the drug's bioavailability, reduce the administered dose, and bring more convenience and compliance for pediatrics with the problem of consuming conventional dosage forms. The optimized colchicine loaded nanofibers of polyvinyl alcohol 10%w/v with 220.47±16.87 nm mean diameter size exhibits smooth surface and continuous structure in SEM micrographs. No incompatibility was seen in FT-IR analyses. The thermal study illustrated stability enhancement by colchicine loading. The water angle analysis demonstrated its superhydrophilicity and the in vitro release profile illustrated a quick release of colchicine in 30 seconds. As a conclusion, nanofiber-based fast dissolving formulation of colchicine could be suggested as a localized and systemic transmucosal delivery system, immediate-release oral dosage form, and even topical colchicine delivery system that may reduce the risk of systemic toxicity in pediatrics. The antitumor property of CL may also suggest it in rapid neoadjuvant or adjuvant localized chemotherapy protocols for the management of topical tumors in pediatrics.