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The potential of liposomes as an intranasal dosage formulation for topical application was investigated in rats. When 5(6)-carboxyfluorescein (CF), a model absorbable drug, dissolved in phosphate-buffered saline (PBS) was administered intranasally, CF was rapidly absorbed into the systemic circulation and no adhesion of CF to the nasal mucosa was observed. The fraction of CF absorbed from the nasal mucosa reached about 48% 1 h after administration. On the other hand, only 3% of the dose was absorbed when CF was encapsulated in liposomes consisting of dipalmitoylphosphatidylcholine and cholesterol (DPPC-liposomes). In addition, the amount of CF adhering to the nasal mucosa after administration as DPPC-liposomes was 20- to 28-fold greater than that in PBS solution. In particular, positively charged liposomes markedly enhanced the adhesion of CF to the nasal mucosa. Differences in the lipid composition of liposomes did not affect the absorption of CF. However, the ability of liposomes to adhere to the nasal mucosa was consistent with the fluidity of the liposomal membrane. Furthermore, the action of liposomes on the anti-histaminic effect of diphenhydramine hydrochloride (DH) was studied in rats by measuring the amount of protein leaking into the nasal cavity under quasi-allergic conditions. The anti-histaminic effect of DH was strong but of short-duration when DH was administered as a PBS solution. However, liposomes prolonged the anti-histaminic effect of DH, suggesting that liposomes may adhere to the nasal mucosa and release DH slowly. In conclusion, liposomes suppress drug absorption into the systemic circulation and concurrently increase drug retention in the nasal cavity.

Usefulness of Liposomes as an Intranasal Dosage Formulation for Topical Drug Application.