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

Rungsinee Phongpradist; Jutamas Jiaranaikulwanitch; Kriangkrai Thongkorn; Suree Lekawanvijit; Sasithorn Sirilun; Chuda Chittasupho; Worrapan Poomanee

doi:10.3390/gels9080610

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

Gels. 2023 Jul 28;9(8):610. doi: 10.3390/gels9080610.

Authors

Rungsinee Phongpradist¹, Jutamas Jiaranaikulwanitch¹, Kriangkrai Thongkorn², Suree Lekawanvijit³, Sasithorn Sirilun¹, Chuda Chittasupho¹, Worrapan Poomanee¹

Affiliations

¹ Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
² Department of Companion Animals and Wildlife Clinic, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand.
³ Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

Abstract

Curcumin is a potent natural compound used to treat Alzheimer's disease (AD). However, the clinical usefulness of curcumin to treat AD is restricted by its low oral bioavailability and difficulty permeating the blood-brain barrier. To overcome such drawbacks, various alternative strategies have been explored, including the transnasal route. However, rapid mucociliary clearance in the nasal cavity is a major hindrance to drug delivery. Thus, designing a delivery system for curcumin to lengthen the contact period between the drug and nasal mucosa must be employed. This study describes the optimization of KLVFF conjugated curcumin microemulsion-base hydrogel (KCMEG) to formulate a prototype transnasal preparation using the response surface method to improve a mucoadhesive property. A central composite design was employed to optimize and evaluate two influencing factors: the concentration of carbopol 940 and the percentage of KLVFF conjugated curcumin microemulsion (KCME). The physicochemical properties, anti-cholinesterase activity, and anti-aggregation activities of KCME were investigated in this study. The studied factors, in terms of main and interaction effects, significantly (p < 0.05) influenced hardness and adhesiveness. The optimized KCMEG was evaluated for pH, spreadability, and mucoadhesive properties. Ex vivo nasal ciliotoxicity to optimize KCMEG was performed through the porcine nasal mucosa. KCME was transparent, with a mean globule size of 70.8 ± 3.4 nm and a pH of 5.80 ± 0.02. The optimized KCMEG containing 2% carbopol 940 showed higher in vitro mucoadhesive potential (9.67 ± 0.13 min) compared with microemulsion and was also found to be free from nasal ciliotoxicity during histopathologic evaluation of the porcine nasal mucosa. The result revealed that both the concentration of carbopol 940 and the percentage of KCME play a crucial role in mucoadhesive properties. In conclusion, incorporating a mucoadhesive agent in a microemulsion can increase the retention time of the formulation, leading to enhanced brain delivery of the drug. Findings from the investigation revealed that KCMEG has the potential to constitute a promising approach to treating AD via transnasal administration.

Keywords: Alzheimer; KLVFF; central composite design; curcumin; microemulsion; microemulsion-based hydrogel; transnasal.

Grants and funding

Chiang Mai University