Folic Acid-Intercalated Mg/Al Layered Double Hydroxides-A Multifunctional Nanohybrid Delivery System for Topical Applications

ACS Omega. 2024 Nov 26;9(49):48185-48195. doi: 10.1021/acsomega.4c05374. eCollection 2024 Dec 10.

Abstract

The delivery of active functional molecules across the skin is laborious due to its structural intricacy and exceptional barrier characteristics. Developments in nanotechnology yielded innovative transport vehicles derived from nanomaterials to reinforce the skin's ability to interact with active ingredient molecules and increase its bioavailability. The current study employed crystalline inorganic two-dimensional double hydroxides (LDHs) as an efficient carrier and delivery vehicle for folic acid (FA) in a topical skincare formulation. FA was incorporated into the interlayer region of Mg/Al LDHs utilizing a coprecipitation procedure to produce a nanohybrid. The nanohybrid was characterized by XRD and FTIR. FA intercalation into the interlayer galleries of the nanohybrid was confirmed by an XRD diffractogram, which established a shift of the basal d (003) reflection of LDHs to lower 2θ angles. FTIR of the nanohybrids revealed the characteristic absorption frequencies of FA, indicating the existence of FA within the LDH matrix. The FA-intercalated nanohybrid showed antioxidant activity similar to that of free FA. A topical formulation was prepared by dispersing FA-intercalated LDH nanohybrid in an oil-in-water (o/w) emulsion, and it was used to evaluate its properties further. Rheological property evaluation showed that the presence of the nanohybrid resulted in better flow behavior and higher yield stress of the formulation, implying improved stability and quality. The nanohybrid also enhanced the storage modulus and, thus, the dynamic rigidity of the formulation. The test compounds expressed no cytotoxicity in HaCaT cells, as cell viability significantly increased in monolayer cultures after a 24-h incubation period. Release studies conducted in vitro using the nanohybrid showed a pH-dependent controlled release of FA. Transdermal permeation experiments using Franz diffusion cells demonstrated a direct correlation between the concentration of penetrated FA with time, which signified a gradual and effective transfer of FA from the LDH matrix into the oil/water emulsion, demonstrating its efficacy. Thus, the study revealed excellent prospects for the nanohybrid as a multifunctional active ingredient in topical applications.