Kao Huei-Jen, Lin Hong-Ru, Lo Yu-Li, Yu Shi-Ping
Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
J Pharm Pharmacol. 2006 Feb;58(2):179-86. doi: 10.1211/jpp.58.2.0004.
Patients using ophthalmic drops are faced with frequent dosing schedules and difficult drop instillation. Therefore, a long-lasting pilocarpine-loaded chitosan (CS)/Carbopol nanoparticle ophthalmic formulation was developed. The physicochemical properties of the prepared nanoparticles were investigated using dynamic light scattering, zeta-potential, transmission electron microscopy, Fourier transform infrared ray spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The sustained-release effects of pilocarpine-loaded nanoparticles were evaluated using in-vitro release and in-vivo miotic tests, and compared with pilocarpine in solution, gel and liposomes. We found that the prepared nanoparticles were about 294 nm in size. DSC and FT-IR studies suggested that an electrostatic interaction between CS and Carbopol contributes at least in part to the stabilization of pilocarpine/CS/Carbopol nanoparticles. When compared with pilocarpine in solution, gel or liposomes, the best slow-release profile of pilocarpine from the prepared nanoparticles occurred in a dissolution test. In the in-vivo miotic study, pilocarpine-loaded CS/Carbopol nanoparticles showed the most significant long-lasting decrease in the pupil diameter of rabbits. The advantages of CS and Carbopol are good biocompatibility, biodegradability and low toxicity. CS is also a mucoadhesive polymer. Thus, pilocarpine/CS/Carbopol nanoparticles may provide an excellent potential alternative ophthalmic sustained-release formulation of pilocarpine for clinical use. CS/Carbopol nanoparticles may also be useful for a variety of other therapeutic delivery systems.
使用眼药水的患者面临着频繁给药方案和滴眼困难的问题。因此，开发了一种负载毛果芸香碱的壳聚糖（CS）/卡波姆纳米颗粒眼用制剂。使用动态光散射、zeta电位、透射电子显微镜、傅里叶变换红外光谱（FT-IR）和差示扫描量热法（DSC）研究了制备的纳米颗粒的物理化学性质。使用体外释放和体内缩瞳试验评估了负载毛果芸香碱纳米颗粒的缓释效果，并与溶液、凝胶和脂质体中的毛果芸香碱进行了比较。我们发现制备的纳米颗粒尺寸约为294nm。DSC和FT-IR研究表明，CS和卡波姆之间的静电相互作用至少部分有助于毛果芸香碱/CS/卡波姆纳米颗粒的稳定。与溶液、凝胶或脂质体中的毛果芸香碱相比，在溶出试验中，制备的纳米颗粒中毛果芸香碱的缓释曲线最佳。在体内缩瞳研究中，负载毛果芸香碱的CS/卡波姆纳米颗粒使兔子瞳孔直径的持久减小最为显著。CS和卡波姆的优点是良好的生物相容性、生物降解性和低毒性。CS也是一种粘膜粘附聚合物。因此，毛果芸香碱/CS/卡波姆纳米颗粒可能为临床使用提供一种极好的潜在替代毛果芸香碱眼用缓释制剂。CS/卡波姆纳米颗粒也可能对多种其他治疗递送系统有用。
