Surface Modification of Curcumin Microemulsions by Coupling of KLVFF Peptide: A Prototype for Targeted Bifunctional Microemulsions

Polymers (Basel). 2022 Jan 22;14(3):443. doi: 10.3390/polym14030443.

Abstract

Curcumin is one of the most promising natural therapeutics for use against Alzheimer's disease. The major limitations of curcumin are its low oral bioavailability and difficulty in permeating the blood-brain barrier. Therefore, designing a delivery system of curcumin to overcome its limitations must be employed. KLVFF, a peptide known as an amyloid blocker, was used in this study as a targeting moiety to develop a targeted drug delivery system. A prototype of transnasal KLVFF conjugated microemulsions containing curcumin (KLVFF-Cur-ME) for the nose-to-brain delivery was fabricated. The KLVFF-Cur-ME was developed by a titration method. A conjugation of KLVFF was performed through a carbodiimide reaction, and the conjugation efficiency was confirmed by FTIR and DSC technique. KLVFD-Cur-ME was characterized for the drug content, globule size, zeta potential, and pH. A transparent and homogeneous KLVFF-Cur-ME is achieved with a drug content of 80.25% and a globule size of 76.1 ± 2.5 nm. The pH of KLVFF-Cur-ME is 5.33 ± 0.02, indicating non-irritation to nasal tissues. KLVFD-Cur-ME does not show nasal ciliotoxicity. An ex vivo diffusion study revealed that KLVFF-Cur-ME partitions the porcine nasal mucosa through diffusion, following the Higuchi model. This investigation demonstrates the successful synthesis of a bifunctional KLVFF-Cur-ME as a novel prototype to deliver anti-Aβ aggregation via an intranasal administration.

Keywords: KLVFF; curcumin; microemulsions; modified Pluronic; surface modification; targeted.