Ophthalmology Operating Room, Xi'an People's Hospital, Xi'an Fourth Hospital, Xi'an, 710004, Shaanxi, China.
Nursing Department, Xi'an People's Hospital, Xi'an Fourth Hospital, Xi'an, 710004, Shaanxi, China.
AAPS PharmSciTech. 2021 Aug 10;22(6):212. doi: 10.1208/s12249-021-02096-6.
The contact lens prepared by the conventional soaking method using timolol-soaking solution showed poor drug uptake and high burst release with altered critical lens properties. In this study, timolol-loaded nanostructured lipid carriers (NLCs) were prepared and evaluated for enhanced timolol uptake and sustained release for the effective management of glaucoma. The characterization studies indicated that timolol-loaded NLCs were spherical in shape with an average size of 130-138 nm and a zeta potential of -46.6 to 51.3 mV. Critical lens properties such as swelling, optical transmittance, and protein adherence were improved with NLC-laden lenses compared to the conventional soaked lenses (SM-TB). Moreover, SM-TB lens showed low timolol uptake, high burst release, and short release duration up to 24 h compared to timolol-NLC-laden lens that showed high timolol uptake, and the cumulative release was sustained up to 96 h. The ability to sustain timolol release improved proportionally with an increase in the amount of Capmul MCMC8 (liquid lipid) in NLCs. In addition, NLC-laden lens was found to be safe according to the results of ocular irritation and histopathological studies. In the rabbit tear fluid model, NLC-30%-Cap-CL batch showed high timolol concentration at all time points up to 60 h. Further, pharmacodynamic study showed sustained reduction in IOP by NLC-30%-Cap-CL batch for 96 h compared to 48 h and 6 h with SM-TB lens and eye drop solution, respectively. In conclusion, NLCs enhanced timolol uptake in the contact lens from the soaking solution using soaking method with improved in vitro and in vivo results for better clinical outcomes in the patients with glaucoma.
传统浸泡法使用噻吗洛尔浸泡溶液制备的隐形眼镜药物摄取率差,突释率高,临界镜片性能发生改变。本研究制备了载有噻吗洛尔的纳米结构脂质载体(NLCs),并对其进行了评价,以增强噻吗洛尔的摄取量和持续释放,从而有效治疗青光眼。特性研究表明,载有噻吗洛尔的 NLCs 呈球形,平均粒径为 130-138nm,Zeta 电位为-46.6 至 51.3mV。与传统浸泡镜片(SM-TB)相比,NLC 载药镜片的临界镜片特性如膨胀性、光透过率和蛋白质附着性得到改善。此外,SM-TB 镜片显示出低的噻吗洛尔摄取量、高的突释释放和短的释放时间(至 24 小时),而载有噻吗洛尔的 NLC 镜片显示出高的噻吗洛尔摄取量,累积释放可持续至 96 小时。随着 NLC 中 Capmul MCMC8(液体脂质)含量的增加,噻吗洛尔释放的持续性也相应提高。此外,根据眼刺激性和组织病理学研究的结果,发现 NLC 载药镜片是安全的。在兔泪液模型中,NLC-30%-Cap-CL 批次在所有时间点(至 60 小时)都显示出高的噻吗洛尔浓度。此外,药效学研究表明,与 SM-TB 镜片和滴眼溶液相比,NLC-30%-Cap-CL 批次可使眼压持续降低 96 小时,而 SM-TB 镜片和滴眼溶液分别可使眼压持续降低 48 小时和 6 小时。综上所述,NLCs 通过浸泡法增强了隐形眼镜对浸泡溶液中噻吗洛尔的摄取,体外和体内结果均得到改善,为青光眼患者带来更好的临床效果。