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本文设计了一种壳聚糖包覆的硝酸毛果芸香碱眼用亚微乳(chitosan-coated pilocarpine nitrate submicroemulsion,CS-PN/SE),旨在开发一种新型的具有黏膜黏附性的亚微乳眼部给药系统,以延长药物在眼表滞留时间,促进药物的眼部吸收。以中长链甘油三酯(medium chain triglycerides,MCT)为油相,Tween 80为主乳化剂,采用高速剪切工艺制备硝酸毛果芸香碱亚微乳(pilocarpine nitrate submicro emulsion,PN/SE),进一步采用孵育法制备CS-PN/SE,并利用星点设计-效应面优化法进行处方优化。对其粒径、zeta电位、包封率和微观形态进行表征,以新西兰白兔为动物模型,评价了CS-PN/SE在兔眼表滞留特性以及缩瞳作用。眼表滞留特性评价结果显示,与硝酸毛果芸香碱溶液剂组(pilocarpine nitrate solution,PNs)和PN/SE组相比,CS-PN/SE组在眼表的清除率下降,KCS-PN/SE为(0.006 4±0.000 3)min-1,平均驻留时间(mean residence time,MRT)延长,为155.4 min(P<0.05)。缩瞳药效学结果显示,CS-PN/SE组的最大缩瞳率为46.3%,缩瞳作用时间长达480 min,较PNs组和PN/SE组分别延长了255 min和105 min,缩瞳率-时间曲线下面积AUC提高为PNs组和PN/SE组的1.6倍和1.2倍(P<0.05)。上述结果表明CS-PN/SE可显著延长药物在眼表滞留时间,增加药物在眼表黏膜层中的渗透力,从而延长缩瞳作用时间,提高药物的眼部生物利用度,实现减少给药频次的目的。
In this paper, chitosan-coated pilocarpine nitrate submicroemulsion (CS-PN / SE) was designed to develop a new type of submucosal eye with mucoadhesiveness Drug delivery system to extend the retention time of drugs in the ocular surface and promote the absorption of the eye of the drug. Medium-length triglyceride (MCT) was used as the oil phase and Tween 80 as the main emulsifier. PN / SE pilocarpine nitrate submicro emulsion (PN / SE) was prepared by high-speed shearing. Method CS-PN / SE was prepared and optimized by the method of star point design-response surface optimization. The particle size, zeta potential, entrapment efficiency and microscopic morphology were characterized. New Zealand white rabbits were used as animal models to evaluate the ocular retention characteristics and the miosis effect of CS-PN / SE in rabbits. The evaluation of ocular surface retentivity showed that the clearance rate of ocular surface in CS-PN / SE group decreased compared with that of pilocarpine nitrate solution (PNs) and PN / SE group (KCS-PN / SE was 0.006 4 ± 0.000 3) min-1, mean residence time (MRT) was prolonged to 155.4 min (P <0.05). The results of miosis pharmacodynamics showed that the maximum mydriasis rate in CS-PN / SE group was 46.3% and the miosis time was 480 min, which was 255 min and 105 min longer than PNs and PN / SE groups, respectively The area under the pupillary rate-time curve AUC increased 1.6-fold and 1.2-fold (P <0.05) for PNs and PN / SE groups. The above results show that CS-PN / SE can significantly prolong drug retention time in the ocular surface, increase the penetration of drugs in the ocular surface mucosal layer, thus prolonging the miosis effect time, improve the ocular bioavailability of the drug, to reduce the administration Frequency of purpose.