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Abstract: Rapamycin-loaded chitosan/polylactic acid nanoparticles with size of about 300nm in diameter were prepared through nanoprecipitation method using cholesterol-modified chitosan as a stabilizer. The surface coating of chitosan, which was demonstrated by zeta potential measurement, endowed the nanoparticles good retention ability at the procorneal area, facilitating the sustained release of rapamycin on the corneal. The immunosuppression in corneal transplantation of the nanoparticles was investigated using rabbit as animal model, the median survival time of the corneal allografts treated with nanoparticles was 27.2±1.03 days and 50% grafts still remained surviving by the end of the observation, while the group treated with 0.5% rapamycin suspension was 23.7±3.20 days. The median survival time of drug-free nanoparticles group and untreated groups were 10.9±1.45 and 10.6±1.26 days, respectively. The results demonstrated the excellent immunosuppression of rapamycin-loaded chitosan/polylactic acid nanoparticles in corneal transplantation. [Copyright &y& Elsevier]

Abstract: Cholesterol hydrophobically modified chitosan (CS-CH) containing 1.7–4.7 cholesterol groups per 100 anhydroglucosamine units of chitosan were synthesized by an EDC-mediated coupling reaction. The physicochemical properties of the self-aggregated nanoparticles in physiological saline were studied using transmission electron microscopy, dynamic light scattering, and fluorescence spectroscopy. The mean diameters of all samples were less than 230nm, and the critical aggregation concentration (CAC) of all self-aggregated nanoparticles in physiological saline less than 4.0×10−2 mg/ml. Both the mean diameters and the CAC decreased slightly with the increasing degree of substitution (DS) by hydrophobic groups. The self-aggregated CS-CH nanoparticles were radiolabeled by 99mTc, their ocular distribution was investigated using single photon emission computed tomography (SPECT) and scintillation counter. The CS-CH nanoparticles retained at the procorneal area, and no radioactivity was found in the posterior segment. The drug-loading and release behavior of the nanoparticles were investigated using Cyclosporine A (CyA) as the model drug. CyA was physically entrapped in the nanoparticles during the dialysis process, and the drug-loading ratio was 6.2%. A sustained release of CyA from CS-CH nanoparticles was observed. The results showed that CS-CH nanoparticles might represent an interesting vehicle to enhance the therapeutic index of clinically challenging drugs with potential application at extraocular level. [Copyright &y& Elsevier]