5-Fluorouracil topical administration

Tear duct fibrosis develops in one of six patients with excessive lacrimation from fluorouracil (66). The eversion of the lower eyelid is reversible with conservative management (68) while the tear duct fibrosis may not be (69). Persistent lacrimation has been described in six patients receiving intravenous fluorouracil weekly for 6-10 months (69). Lacrimation persisted in five patients after the withdrawal of fluorouracil, suggesting an irreversible dacryostenosis. Lacrimal duct stenosis has also been reported (70). Bilateral cicatricial ectropion was also reported in a patient after topical administration of fluorouracil for the treatment of multiple facial actinic keratoses (71). If ectropion and tear duct stenosis progress, surgical correction may be required. 

Galentine P, Sloas H, Hargett N, Cupples HP. Bilateral cicatricial ectropion following topical administration of 5-fluorouracil. Ann Ophthalmol 1981 13(5) 575-7. 

Other routes of administration can be employed in certain situations. Methotrexate and cytarabine are given intrathecally or intraventricularly to prevent relapses in the meninges in acute lymphocytic leukemia and to treat carcinomatous meningitis. Thiotepa and bleomycin have been administered by intravesical instillation to treat early bladder cancers. Fluorouracil can be applied topically for certain skin cancers. 

Prolonged-release (or slow-release) preparations are useful for water-soluble drugs with short biological half-lives. Hydrophobic CyDs, such as ethylated CyDs, with low aqueous solubilities have been demonstrated to work as slow-release carriers of water-soluble drugs such as isosorbide dinitrate, diltiazem hydrochloride, and 5-fluorouracil [19, 38, 39]. For example, 15 has the most prominent retarding effect for water-soluble molsidomine and diltiazem hydrochloride, after oral administration in dogs. The release of isosorbide dinitrate from 16 film was retarded and the plasma drug level after topical application of the film to rat abdominal skin was maintained at 100 ng mL for about 10 h [41]. 

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