Nasotransmucosal Delivery of Curcumin-Loaded Mucoadhesive Microemulsions for Treating Inflammation-Related CNS Disorders.

Abstract

This investigation was aimed at designing an effective mucoadhesive microemulsion system to accomplish higher brain uptake of curcumin through intranasal route. Mucoadhesive microemulsion of curcumin (MMEC) was developed using screened oil, surfactant, and co-surfactant by Box-Behnken design and was evaluated for mucoadhesion, stability, and naso-ciliotoxicity study. Comparative brain uptake of curcumin after nasal administration of MMEC and polycarbophil curcumin gel and intravenous administration of plain curcumin solution was studied by performing bio-distribution study in Swiss albino rats. The results showed that all formulation variables i.e., the amount of capmul MCM (X1), Smix (accenon CC: transcutol P) (X2) and percentage of aqueous. Polycarbophil (X3) had a significant effect (p<0.05) on the responses. The developed MMEC was stable and non-ciliotoxic with 66.74 ± 3.46 nm and 98.58% ± 1.21 as average globule size and drug content, respectively. Polydispersibility index (0.133 ± 0.17) data and transmission electron microscopy study depicted the narrow size distribution of MMEC. Furthermore, following a comparative investigation of the brain uptake of curcumin among MMEC, plain drug gel and intravenous administration at 2.86 mg/kg, more brain uptake of curcumin was demonstrated for MMEC over intravenous application. Moreover, curcumin uptake in olfactory bulb after nasal administration of MMEC (31.11 ± 1.6) was than 9.44 times higher than intravenous injection of curcumin solution (3.25 ± 1.01). Area under curve represents the ratio of 2.86 mg/kg in brain tissue to plasma acquired afterward(s) the intranasal injection of MMEC (and it) was essentially greater than after the intravenous administration of curcumin solution. Findings of the investigation revealed that optimal MMEC and intranasal route may be considered to be promising and an alternative approach for brain targeting of curcumin.