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聚乙二醇化壳聚糖纳米粒的制备及局部滴眼给药性能评价
Preparation and performance of PEGylated chitosan nanoparticles for ocular drug delivery by eye drops
- 第三军医大学学报 2017年39卷第13期 页码：1376-1380
- 作者机构：
1.402160 重庆，重庆医科大学附属永川医院：眼科
2.402160 重庆，重庆医科大学附属永川医院：中心实验室
- 作者简介：
[刘世纯, 电话:(023)85381640，E-mail: nanomed@163.com LIU Shichun, Tel: 86-23-85381640, nanomed@163.com
- 基金信息：
DOI：10.16016/j.1000-5404.201612057
中图分类号： R944.9;R969;R988.1收稿：2016-12-08，
修回：2017-03-13，
纸质出版：2017-07-15
- 稿件说明：
移动端阅览
徐霁, 周文君, 蔡春华, 等. 聚乙二醇化壳聚糖纳米粒的制备及局部滴眼给药性能评价[J]. 第三军医大学学报, 2017,39(13):1376-1380.
Ji XU, Wenjun ZHOU, Chunhua CAI, et al. Preparation and performance of PEGylated chitosan nanoparticles for ocular drug delivery by eye drops[J]. Journal of Third Military Medical University, 2017, 39(13): 1376-1380.
徐霁, 周文君, 蔡春华, 等. 聚乙二醇化壳聚糖纳米粒的制备及局部滴眼给药性能评价[J]. 第三军医大学学报, 2017,39(13):1376-1380. DOI： 10.16016/j.1000-5404.201612057.
Ji XU, Wenjun ZHOU, Chunhua CAI, et al. Preparation and performance of PEGylated chitosan nanoparticles for ocular drug delivery by eye drops[J]. Journal of Third Military Medical University, 2017, 39(13): 1376-1380. DOI： 10.16016/j.1000-5404.201612057.
摘要
目的
2
制备一种聚乙二醇修饰的壳聚糖纳米粒，评价其局部滴眼给药性能。
方法
2
以伏立康唑为模型药物，采用离子交联法制备载药的聚乙二醇化壳聚糖纳米粒，对其进行表征后，分别考察纳米粒的药物缓释能力、对眼表药物代谢动力学的影响及其角膜渗透性。
结果
2
聚乙二醇化壳聚糖纳米粒粒径为(235±23) nm，Zeta电位为(+23.1±0.6) mV，载药量为11.16%，包封率为61.35%。纳米粒体外释放药物非常缓慢，可持续释药48 h；相比于伏立康唑水溶液，纳米粒的药物浓度-时间曲线下面积明显增加，药物半衰期延长，清除率减少，眼表药物平均滞留时间延长(
P
＜0.05)。荧光标记的聚乙二醇化壳聚糖纳米粒可穿透角膜上皮逐渐向角膜基质渗透。
结论
2
与药物水溶液相比，聚乙二醇化壳聚糖纳米粒能够有效减少眼表药物的流失，改善药物的生物利用度。
Abstract
Objective
2
To develop a polyethylene glycol modified (PEGylated) chitosan nanoparticle and evaluate its potential for ocular drug delivery by eye drops.
Methods
2
Voriconazole was employed as model drug. The PEGylated chitosan nanoparticles were prepared by ionotropic gelification and characterized for the properties.
In vitro
drug release properties
ocular pharmacokinetics and corneal penetration of these nanoparticles were studied.
Results
2
The PEGylated chit
osan nanoparticle was 235±23 nm in particle size
23.1±0.6 mV in zeta potential
11.16% of drug loading capacity
and 61.35% of encapsulation efficiency. The sustained drug was released very slowly from the nanoparticles
for consecutive 48 h. Compared with voriconazole solution
the nanoparticles had significantly increased area under the concentration-time curve
prolonged half-life and decreased clearance rate of the loaded drug
and prolonged residence time at the ocular surface (
P
<
0.05). The corneal penetration study with the aid of fluorescent labeled nanoparticles showed that the nanoparticles could penetrate into the cornea.
Conclusion
2
Compared with the aqueous solution
the PEGylated chitosan nanoparticle could prevent the drug loss on ocular surface and improve the drug bioavailability.
关键词
Keywords
references
URTTI A. Challenges and obstacles of ocular pharmacokinetics and drug delivery[J]. Adv Drug Deliv Rev, 2006, 58(11): 1131-1135. DOI:10.1016/j.addr.2006.07.027.
SHARMA K, SOMAVARAPU S, COLOMBANI A, et al . Crosslinked chitosan nanoparticle formulations for delivery from pressurized metered dose inhalers[J ] . EurJPharm Biopharm, 2012, 81(1): 74- 81. DOI: 10.1016/j.ejpb.2011.12.014.
CHENMC, MIFL, LIAOZX, et al . Recent advances in chitosan-based nanoparticles for oral delivery of macromolecules[J ] . Adv Drug Deliv Rev, 2013, 65(6): 865-879. DOI:10.1016/j.addr.2012.10.010.
RAGELLE H, RIVA R, VANDERMEULEN G, et al . Chitosan nanoparticles for siRNA delivery: optimizing formulation to increase stability and efficiency[J ] . JControl Release, 2014, 176: 54-63. DOI:10.1016/j.jconrel.2013.12.026.
SCHELLEKENS H, HENNINKWE, BRINKS V. The immunogenicity of polyethylene glycol: facts and fiction[J]. Pharm Res, 2013, 30(7): 1729-1734. DOI:10.1007/s11095-013-1067-7.
D'SOUZAAA, SHEGOKAR R. Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications[J]. Expert Opin Drug Deliv, 2016, 13(9): 1257-1275. DOI:10.1080/17425247.2016.1182485.
乔从德.聚乙二醇基智能水凝胶的研究进展[J].高分子通报, 2010(3): 23-30. DOI:10.14028/j.cnki.1003-3726.2010.03.001.
QIAOCD. Progress of PEG-based hydrogel[J]. Chin Polymer Bull, 2010(3): 23-30. DOI:10.14028/j.cnki.1003-3726.2010.03.001.
赵媛. 加替沙星壳聚糖纳米粒子的制备、体外性质研究及眼表毒性实验[D]. 重庆: 重庆医科大学, 2010.
ZHAO Y. Chitosan nanoparticles asapotential vehicle for gatifloxacein in ocular delivery: preparation, characterIzateon and toxicity concerns in vivo[D]. Chongqing:Chongqing Medical University, 2010.
SAHOOSK, DILNAWAZ F, KRISHNAKUMAR S. Nanotechnology in ocular drug delivery[J]. Drug Discov Today, 2008, 13(3/4): 144-151. DOI:10.1016/j.drudis.2007.10.021.
ELJARRAT-BINSTOCK E, PE'ER J, DOMBAJ. New techniques for drug delivery to the posterior eye segment[J]. Pharm Res, 2010, 27(4): 530-543. DOI: 10.1007/s11095-009-0042-9.
GAUDANA R, JWALA J, BODDUSH S, et al . Recent perspectives in ocular drug delivery[J ] . Pharm Res, 2009, 26(5): 1197-1216. DOI: 10.1007/s11095-008-9694-0.
MATHIYALAGAN R, SUBRAMANIYAM S, KIMYJ, et al . Synthesis and pharmacokinetic characterization ofapH-sensitive polyethylene glycol ginsenoside CK (PEG-CK) conjugate[J ] . Biochemistry & Molecular Biology(Notes), 2014, 78(3): 466-468. DOI:10.1080/09168451.2014.885827.
ZHOU S, DENG X, LI X. Investigation onanovel core-coated microspheres protein delivery system[J]. JControl Release, 2001, 75(1/2): 27-36. DOI:10.1016/S0168-3659(01)00379-0.
WADHWA S, PALIWAL R, PALIWALSR, et al . Hyaluronic acid modified chitosan nanoparticles for effective management of glaucoma: development, characterization, and evaluation[J ] . JDrug Target, 2010, 18(4): 292-302. DOI:10.3109/10611860903450023.
SARGEANTTD, DESAIAP, BANERJEE S, et al . An in situ forming collagen-PEG hydrogel for tissue regeneration[J ] . Acta Biomater, 2012, 8(1): 124-132. DOI:10.1016/j.actbio.2011.07.028.
AGARWAL R, IEZHITSA I, AGARWAL P, et al . Liposomes in topical ophthalmic drug delivery: an update[J ] . Drug Deliv, 2016, 23(4): 1075-1091. DOI: 10.3109/10717544.2014.943336.
SOUZAJG, DIAS K, SILVASA, et al . Transcorneal iontophoresis of dendrimers: PAMAM corneal penetration and dexamethasone delivery[J ] . JControl Release, 2015, 200: 115-124. DOI:10.1016/j.jconrel.2014.12.037.
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