Novel oleyl amine-modified polymannuronic acid micelle loading tacrolimus for therapy of allergic conjunctivitis

Marine polysaccharide-based nanomaterial attracted considerable attention due to its biocompatibility and biodegradability. Here, a novel polymannuronic acid derivative (PM-C₁₈) was synthesized as nanocarrier modified with hydrophobic oleyl amine. Its structure was confirmed by Fourier-transformed infrared spectrometry and nuclear magnetic resonance. To investigate its function, we developed tacrolimus (FK506) loaded nanoparticle by self-assembling PM-C₁₈ and studied its drug loading, cytotoxicity and mechanism of in vitro release. Furthermore, we established a mouse model of allergic conjunctivitis (AC) to evaluate the efficacy of FK506 loaded PM-C₁₈. The results indicated that PM-C₁₈ carrier can encapsule FK506 with high drug loading (18%) and average particle size of 110.34±1.6nm. The release mechanism was diffusion initially followed a lasting release induced by swelling and collapse of PM-C₁₈. One-week treatment with FK506 loaded PM-C₁₈ efficiently relieved the symptoms of AC, which indicated it could serve as a potential ophthalmic drug for patients with AC. Compared with FK506 ophthalmic suspension, FK506 loaded PM-C₁₈ improved medication adherence_. Most importantly, we developed a novel versatile nanomaterial of PM-C₁₈ which could encapsule other active agents for more applications.