κ-Carrageenan/Aloe vera-based bigels for sustained topical drug delivery: Design, characterization and melatonin...

The primary aim of this study is to develop an innovative κ-Carrageenan (κ-CA)/Aloe vera-based bigel system that enables controlled drug release for topical applications. Melatonin, an amphiphilic compound with inherently low bioavailability, was selected as the model drug to evaluate the performance of the developed bigel systems. Stable bigels were prepared at room temperature by mixing a κ-CA/Aloe vera-based hydrogel with an Aloe vera oil-based organogel at various hydrogel-to-organogel (H:O) ratios (90:10, 70:30, 50:50, 30:70, and 10:90). Morphological analysis revealed that the formulation with a 70:30 (H:O) ratio exhibited large (~300 μm), spherical, and transparent organogel droplets homogeneously dispersed within the hydrogel matrix, forming a typical bigel structure. Physical, chemical, mechanical, and rheological analyses demonstrated that this formulation exhibited superior thermal and structural stability, with a hardness of approximately 1 N, an oil binding capacity of ~95%, a crystallinity degree of ~13%, and a melting temperature of 67 °C. Cell culture studies confirmed that both empty and melatonin-loaded bigels were non-toxic. In vitro cumulative melatonin release reached approximately 0.36 mg within five days, with release kinetics consistent with the Higuchi and Korsmeyer-Peppas models. Ex vivo permeation studies using pig ear skin demonstrated that the 70:30 (H:O) bigel formulation enhanced skin penetration by crossing the stratum corneum barrier, yielding a cumulative melatonin amount of approximately 0.33 mg after 24 h. These findings highlight that the κ-CA/Aloe vera-based bigel system may be a promising platform for controlled topical delivery of amphiphilic drugs.