Wang Fengzhen, Chen Li, Zhang Dongsheng, Jiang Sunmin, Shi Kun, Huang Yuan, Li Rui, Xu Qunwei
School of Pharmacy, Nanjing Medical University , Nanjing, Jiangsu , China .
J Drug Target. 2014 Nov;22(9):849-58. doi: 10.3109/1061186X.2014.939983. Epub 2014 Jul 21.
The aims of this study were to design and characterize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLN) with and without modification of low molecular weight chitosan (CS) and compare their potentials for ocular drug delivery. Low molecular weight CS was obtained via a modified chemical oxidative degradation method. SLN with CS (CS-SLN-MTZ) and without CS (SLN-MTZ) were prepared according to a modified emulsion-solvent evaporation method. SLN-MTZ and CS-SLN-MTZ were 199.4 ± 2.8 nm and 252.8 ± 4.0 nm in particle size, -21.3 ± 1.9 mV and +31.3 ± 1.7 mV in zeta potential, respectively. Physical stability studies demonstrated that CS-SLN-MTZ remained stable for at least 4 months at 4 °C, while SLN-MTZ no more than 2 months. A prolonged in vitro release profile of MTZ from CS-SLN-MTZ was obtained compared with SLN-MTZ. Furthermore, CS-SLN-MTZ presented a better permeation property in excised rabbit cornea. In vivo studies indicated that the intraocular pressure lowering effect of CS-SLN-MTZ (245.75 ± 18.31 mmHg × h) was significantly better than both SLN-MTZ (126.74 ± 17.73 mmHg × h) and commercial product Brinzolamide Eye Drops AZOPT® (171.17 ± 16.45 mmHg × h). The maximum percentage decrease in IOP of CS-SLN-MTZ (42.78 ± 7.71%) was higher than SLN-MTZ (27.82 ± 4.15%) and was comparable to AZOPT (38.06 ± 1.25%). CS-SLN-MTZ showed no sign of ocular irritancy according to the Draize method and the histological examination.
本研究的目的是设计并表征负载甲醋唑胺（MTZ）的固体脂质纳米粒（SLN），包括未修饰和经低分子量壳聚糖（CS）修饰的情况，并比较它们用于眼部给药的潜力。低分子量CS通过改良的化学氧化降解法获得。采用改良的乳化溶剂蒸发法制备了含CS的SLN（CS-SLN-MTZ）和不含CS的SLN（SLN-MTZ）。SLN-MTZ和CS-SLN-MTZ的粒径分别为199.4±2.8nm和252.8±4.0nm，ζ电位分别为-21.3±1.9mV和+31.3±1.7mV。物理稳定性研究表明，CS-SLN-MTZ在4℃下至少可稳定4个月，而SLN-MTZ不超过2个月。与SLN-MTZ相比，CS-SLN-MTZ呈现出MTZ更长的体外释放曲线。此外，CS-SLN-MTZ在离体兔角膜中表现出更好的渗透性能。体内研究表明，CS-SLN-MTZ的降眼压效果（245.75±18.31mmHg×h）显著优于SLN-MTZ（126.74±17.73mmHg×h）和市售产品布林佐胺滴眼液AZOPT®（171.17±16.45mmHg×h）。CS-SLN-MTZ眼压降低的最大百分比（42.78±7.71%）高于SLN-MTZ（27.82±4.15%），与AZOPT（38.06±1.25%）相当。根据Draize方法和组织学检查，CS-SLN-MTZ未显示出眼部刺激迹象。
