Polydopamine coated surfactin micelles for brain delivery of ibudilast in multiple sclerosis: Design, optimization, in vitro and in vivo evaluation

Abstract

Ibudilast inhibits TNF-α and IL-12 release from the astrocytes and microglial cells, reducing neuronal degeneration and may be a potential therapy in multiple sclerosis with neuroprotective effects. Our study aimed to prepare polydopamine coated micelles of surfactin, a biosurfactant, loaded with ibudilast to control the release and its targeted delivery through nose to the brain by targeting D2-like dopamine receptors limited in olfactory nerve of the bulb. Micelles were prepared by solvent evaporation and film hydration method and optimized to quantify the effects of excipients on particle size and entrapment efficiency. Polydopamine coating on the surface of surfactin micelles was characterized by studying the physicochemical properties of the micelles. Drug concentration in brain after 14 days of administration of the oral, and nasal free drug and also 3 doses of intranasal PDA coated micelles of ibudilast were determined by reverse-phase HPLC method. FTIR results confirmed successful coating of PDA on surfactin micelles and DSC and XRD results indicated solubilization of ibudilast in the core of micelles in an amorphous state. The morphology of the micelles by TEM showed spherical structures with coating of PDA on the shell of the micelles. Particle size of the micelles was 131.3 ± 12.6 nm, zeta potential 27.3 ± 1.7 mV, ibudilast loading percent was 90.2 ± 1.6% and drug release efficiency percent was 72.3 ± 6.5% in the best formulation for surfactin micelles. However, after PDA coating the particle size changed to 174.6 ± 15.7 nm, zeta potential varied to −41.0 ± 2.7 mV, PDA content was 70.3 ± 5.2%, and drug release efficiency percent was 52.9 ± 2.9%. Ibudilast brain concentration was significantly (p < 0.05) higher in PDA coated micelles than oral or nasal free drug.