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

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.

The Anti-Aggregative Peptide KLVFF Mimics Aβ1-40 in the Modulation of Nicotinic Receptors: Implications for Peptide-Based Therapy

“…Therefore, the ability to block only the derangement of this protein could be relevant to the success of the amyloid-based strategy. Different compounds can interfere with amyloid aggregation and, in particular, promising results have been obtained using amyloid fragments [ 16 , 17 , 18 ].…”

“…The KLVFF-based prototypes have been extensively discussed in the literature [ 16 , 17 , 18 ]. The scientific community agrees on the anti-aggregative properties of this small fragment [ 52 , 53 , 54 ].…”

“…The authors describe peptides as the most promising tools among metal chelators, nanostructures, organic molecules, peptide mimics, and antibodies. The literature consistently shows that a short peptide (KLVFF), derived from the cleavage of Aβ, can interfere with amyloid aggregation [ 16 , 17 , 18 ]. Considering the possibility of using this peptide therapeutically, we need to define the pharmacological and toxicological profile and highlight the potential targets involved.…”

KLVFF Conjugated Curcumin Microemulsion-Based Hydrogel for Transnasal Route: Formulation Development, Optimization, Physicochemical Characterization, and Ex Vivo Evaluation

“…According to our previous result, the suitable formulation consisted of oleic acid as the oil phase, a mixture of Tween 80 and KLVFF-Pluronic F127 in the ratio 1:1 (surfactant), ethanol (co-surfactant) as a mixture of surfactant and co-surfactant (S mix ), and water as the aqueous phase. We reported that the most suitable ME component was 15:80:5 for the oil:S mix :water ratio, respectively [ 71 ] This microemulsion component exhibited optimal results and was chosen to create KCME in this study. Curcumin (0.9 mg/mL) was dissolved in the oil phase by adding the required amount of S mix and water and stirring to create a clear, yellow, and transparent dispersion.…”

Composite of KLVFF-Transthyretin-Penetratin and Manganese Dioxide Nanoclusters: A Multifunctional Agent against Alzheimer’s β-Amyloid Fibrillogenesis

“…Although Pen-functionalized nanoparticles can cross the BBB, the nanoparticles still hardly accumulated in the lesion site due to the lack of targeting capability. As for delivery of Aβ inhibitors, KLVFF from the central hydrophobic core (CHC) region of Aβ can serve as an Aβ-targeting peptide [ 39 ]. For instance, Plissonneau et al grafted KLVFF onto nanoparticles, thereby conferring upon them the ability to recognize and bind to amyloid plaques in the mouse hippocampus [ 40 ].…”