Preparation and Characterization of Novel Pimecrolimus Nanoparticles for Therapy of Allergic Conjunctivitis

Pimecrolimus is a novel anti-inflammatory drug for treating allergic conjunctivitis. However, its high hydrophobicity is the bottleneck for clinical application on anti-allergic conjunctivitis. Although ongoing efforts have been made to increase its hydrophilicity through hydration, the results are discouraging. Now, we developed the nanoparticle-encapsule of pimecrolimus in a new material synthesized from polymannuronic acid and oleyl amine. The drug loading and encapsulation efficiency of pimecrolimus nanoparticle were measured by high-performance liquid chromatography, which were 12.38 +/- 0.04% and 94.58 +/- 0.07%, respectively. The mean particle size of pimecrolimus nanoparticle was 193.1 +/- 2.62 nm and polydisperse index was 0.176 +/- 0.018. Its spherical and homogeneous appearance were observed by transmission electron microscope. Furthermore, a mouse model of allergic conjunctivitis has been established to evaluate the efficacy of pimecrolimus nanoparticle. Treatment progress with clinical scoring and morphology of the conjunctiva histology were assessed in detail. The results have demonstrated that pimecrolimus nanoparticle could significantly relieve the inflammation signs of allergic conjunctivitis model mice and repair ocular surface goblet cells after a week of treatment twice a day. The improvement rate and inflammatory cell inhibition rate of the free pimecrolimus group versus pimecrolimus nanoparticle group were (49.18% vs. 71.26%), (67.43% vs. 81.18%), respectively. Such data further demonstrated pimecrolimus nanoparticle could be a good candidate as a promising ophthalmic agent for treating allergic conjunctivitis, meanwhile, a novel biodegradable seaweed polysaccharide derivative should be a potential carrier for lipophilic drug.