Green preparation, characterization, evaluation of anti-melanogenesis effect and in vitro/in vivo safety profile of kojic acid hydrogel as skin lightener formulation

Abstract

The local treatment of kojic acid (KA) as a tyrosinase inhibitor results in inadequate skin absorption and a number of side effects. The current study aims to maximize KA skin delivery. To produce KA-hydrogel, 1% KA was injected into a Chitosan/alginate hydrogel. The impacts of biopolymer proportion on the KA-hydrogel preparations were investigated. Swelling analysis, weight loss analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), UV absorption spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to evaluate the KA-hydrogel. The swelling percentages of KA-hydrogel increased significantly after 4 h. After two weeks, up to 60% of the primary mass of the KA- hydrogel has been removed. By alternation in biopolymer proportion, the drug release profile of KA-hydrogel demonstrated a sustained pattern. According to the skin absorption experiment, KA-hydrogel had higher skin deposition (25.630 ± 3.350%) than KA-plain gel (5.170 ± 0.340%). Moreover, an in vitro cytotoxicity analysis for the modified KA-hydrogel preparations revealed no cytotoxic effects on HFF cell line (90%). Moreover, KA hydrogel had inhibitory effect on melanin synthesis and are comparable with KA. Furthermore, KA-hydrogel had higher inhibitory effect on L-dopa auto oxidation (94.84 ± 2.41%) in comparison KA solution (73.95 ± 3.28%). Also, the dermal irritation study on Wistar rat revealed that the hydrogel constituent used did not irritate the skin. These results revealed that the KA-hydrogel might be employed as KA local administration, thus opening up new prospects for the therapies of hyperpigmentation problems.

Keywords:

• Kojic acid
• hydrogel
• percutaneous delivery
• hyperpigmentation disorders
• melanin count

Author contribution

Zahra Rezanejad Gatabi: Methodology, Investigation, Writing original draft

Majid Saeedi: Supervision, review & editing

Katayoun Morteza-Semnani^: Supervision

Seyyed Mohammad Hassan Hashemi^: Writing-review & editing

Seyyed Mobin Rahimnia: Methodology, Investigation

Rezvan Yazdian-Robati: Methodology, Investigation

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The current work has been supported by the Research Council of Mazandaran University of Medical Sciences.