Formulation Feasibility of a Mechanically Compliant Stearate Organogel–Methylcellulose/Gelatin Bigel for Localized Neurotherapeutic Delivery

Abstract

Traumatic brain injury (TBI) presents a mechanically sensitive and pharmacologically complex environment in which therapeutic delivery remains challenging. Bigels may offer a formulation strategy for incorporating therapeutics with differing physicochemical properties while providing soft, viscoelastic matrices with properties that may be relevant to neural delivery applications. This study evaluated the in vitro formulation feasibility of a biphasic stearate organogel–methylcellulose/gelatin bigel as a mechanically compliant biphasic vehicle for localized delivery of neurotherapeutic agents. Bigels were fabricated by hot emulsification and genipin crosslinking to generate hydrogel-dominant dual-phase systems. Hydrogel:organogel formulations of 95:5 (BG1) and 85:15 (BG2) showed storage moduli of approximately 250 Pa and 200 Pa, respectively, and compressive Young’s moduli of 0.39 and 0.70 kPa, within reported ranges for soft brain tissue. Stress relaxation confirmed viscoelastic behaviour, while minimal oil leakage (<0.2%) indicated phase stability. BG1 showed 52% porosity, pore sizes of 1.8–22 µm, and approximately 14% weight gain. Drug release followed Weibull kinetics (R2 = 0.99–0.999), with nicotinamide showing faster release and N-acetylcysteine and TPGS showing more sustained release. Both unloaded and drug-loaded bigels maintained >70% PC12 cell viability. These findings support the formulation feasibility of biphasic bigels as mechanically compliant vehicles capable of accommodating therapeutics with differing physicochemical properties and exhibiting differential release behaviour. Further studies are required to evaluate degradation, tissue interactions, retention, and therapeutic performance in advanced in vitro and in vivo models.