In vitro kinetic release study, antimicrobial activity and in vivo toxicity profile of a kojic acid ester-based nanoemulsion for topical application

Sharifah Nurfadhlin Afifah Syed Azhar; Siti Efliza Ashari; Syahida Ahmad; Norazlinaliza Salim

doi:10.1039/d0ra04807k

In vitro kinetic release study, antimicrobial activity and in vivo toxicity profile of a kojic acid ester-based nanoemulsion for topical application

RSC Adv. 2020 Dec 9;10(71):43894-43903. doi: 10.1039/d0ra04807k. eCollection 2020 Nov 27.

Authors

Sharifah Nurfadhlin Afifah Syed Azhar¹, Siti Efliza Ashari^{1

2}, Syahida Ahmad³, Norazlinaliza Salim^{1

2}

Affiliations

¹ Integrated Chemical BioPhysics Research Centre, Faculty of Science, Universiti Putra Malaysia 43400 UPM Serdang Selangor Malaysia ctefliza@upm.edu.my.
² Centre of Foundation Studies for Agricultural Science, Universiti Putra Malaysia 43400 UPM, Serdang Selangor Malaysia.
³ Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia 43400 UPM Serdang Selangor Malaysia.

Abstract

Nanoemulsions have emerged as novel vehicles for drug delivery that allow sustained or controlled release for topical application. In this study, kojic acid ester-based nanoemulsion (KAE-NA) was analyzed for in vitro permeation evaluation, kinetic release study, in vitro antimicrobial activity and in vivo toxicity profile on embryonic zebrafish (Danio rerio). Based on KAE-NA in vitro permeation evaluation, the percentage of permeation was significantly improved from 4.94% at 1 h to 59.64% at 8 h of application. The permeation rate of KAE-NA at 8 h was 4659.50 μg cm^-2 h^-1 (initial concentration, C ₀ = 2000 μg mL^-1) with a permeability coefficient (K _p) value of 0.48 cm h^-1. The kinetic release analysis showed the Korsmeyer-Peppas model was the best fitted kinetic model with high linearity [R ² = 0.9964]. Antimicrobial activity of KAE-NA was studied against the skin pathogen bacteria Staphylococcus aureus ATCC 43300. The results indicated that the inhibition zone size of the KAE-NA (8.00 ± 0.0 mm) was slightly bigger than that of its active ingredient, kojic acid ester (6.5 ± 0.0 mm). The toxicity profile of KAE-NA on embryonic zebrafish revealed less toxicity with LC₅₀ (50% lethal concentration) more than 500 μg mL^-1. The survival rate of the embryonic zebrafish was more than 80% when treated at doses ranging from 7.81-250 μg mL^-1 and showed normal development throughout the experiment without any observed deformation. Hence, KAE-NA proved to be less toxic on the embryonic zebrafish.