Abstract

Recently, various novel drug delivery systems have been developed to overcome ocular barriers in order to improve drug efficacy. We have previously reported that montmorillonite (MT) microspheres (MPs) and solid lipid nanoparticles (SLNs) loaded with the anti-glaucoma drug betaxolol hydrochloride (BHC) exhibited sustained drug release and thus intraocular pressure (IOP) lowering effects. Here, we investigated the effect of physicochemical particle parameters on the micro-interactions with tear film mucins and corneal epithelial cells. Results showed that the MT-BHC SLNs and MT-BHC MPs eye drops significantly prolonged the precorneal retention time due to their higher viscosity and lower surface tension and contact angle compared with the BHC solution, with MT-BHC MPs exhibiting the longest retention due to their stronger hydrophobic surface. The cumulative release of MT-BHC SLNs and MT-BHC MPs was up to 87.78% and 80.43% after 12 h, respectively. Tear elimination pharmacokinetics study further confirmed that the prolonged precorneal retention time of the formulations was due to the micro-interaction between the positively charged formulations and the negatively charged tear film mucins. Moreover, the area under the IOP reduction curve (AUC) of MT-BHC SLNs and MT-BHC MPs was 1.4 and 2.5 times that of the BHC solution. Accordingly, the MT-BHC MPs also exhibit the most consistent and long-lasting IOP-lowering effect. Ocular irritation experiments showed no significant toxicity of either. Taken together, MT MPs may have the potential for more effective glaucoma treatment.

摘要

最近，已经开发了各种新型药物递送系统来克服眼部障碍以提高药物疗效。我们之前曾报道过载有抗青光眼药物盐酸倍他洛尔 (BHC) 的蒙脱石 (MT) 微球 (MP) 和固体脂质纳米颗粒 (SLN) 表现出持续的药物释放，从而降低眼压 (IOP)。在这里，我们研究了物理化学颗粒参数对与泪膜粘蛋白和角膜上皮细胞的微相互作用的影响。结果表明，与 BHC 溶液相比，MT-BHC SLNs 和 MT-BHC MPs 滴眼液由于其更高的粘度和更低的表面张力和接触角，显着延长了角膜前保留时间，其中 MT-BHC MPs 表现出最长的保留时间，因为它们更强的疏水表面。12 小时后，MT-BHC SLNs 和 MT-BHC MPs 的累积释放量分别高达 87.78% 和 80.43%。泪液消除药代动力学研究进一步证实，延长的制剂角膜前滞留时间是由于带正电荷的制剂与带负电荷的泪膜粘蛋白之间的微相互作用。此外，MT-BHC SLN 和 MT-BHC MPs 的 IOP 降低曲线下面积 (AUC) 是 BHC 溶液的 1.4 和 2.5 倍。因此，MT-BHC MPs 也表现出最一致和最持久的 IOP 降低效果。眼部刺激实验表明两者均无明显毒性。总之，MT MPs 可能具有更有效治疗青光眼的潜力。泪液消除药代动力学研究进一步证实，延长的制剂角膜前滞留时间是由于带正电荷的制剂与带负电荷的泪膜粘蛋白之间的微相互作用。此外，MT-BHC SLN 和 MT-BHC MPs 的 IOP 降低曲线下面积 (AUC) 是 BHC 溶液的 1.4 和 2.5 倍。因此，MT-BHC MPs 也表现出最一致和最持久的 IOP 降低效果。眼部刺激实验表明两者均无明显毒性。总之，MT MPs 可能具有更有效治疗青光眼的潜力。泪液消除药代动力学研究进一步证实，延长的制剂角膜前滞留时间是由于带正电荷的制剂与带负电荷的泪膜粘蛋白之间的微相互作用。此外，MT-BHC SLN 和 MT-BHC MPs 的 IOP 降低曲线下面积 (AUC) 是 BHC 溶液的 1.4 和 2.5 倍。因此，MT-BHC MPs 也表现出最一致和最持久的 IOP 降低效果。眼部刺激实验表明两者均无明显毒性。总之，MT MPs 可能具有更有效治疗青光眼的潜力。此外，MT-BHC SLN 和 MT-BHC MPs 的 IOP 降低曲线下面积 (AUC) 是 BHC 溶液的 1.4 和 2.5 倍。因此，MT-BHC MPs 也表现出最一致和最持久的 IOP 降低效果。眼部刺激实验表明两者均无明显毒性。总之，MT MPs 可能具有更有效治疗青光眼的潜力。此外，MT-BHC SLN 和 MT-BHC MPs 的 IOP 降低曲线下面积 (AUC) 是 BHC 溶液的 1.4 和 2.5 倍。因此，MT-BHC MPs 也表现出最一致和最持久的 IOP 降低效果。眼部刺激实验表明两者均无明显毒性。总之，MT MPs 可能具有更有效治疗青光眼的潜力。