Size-dependent disposition of nanoparticles and microparticles following subconjunctival administration
Size-dependent disposition of nanoparticles and microparticles following subconjunctival administration
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DOI：
10.1211/jpp.57.12.0005
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发表时间：
2005-12-01
影响因子：
3.3
通讯作者：
Kompella, UB
中科院分区：
文献类型：
--
作者：
Amrite, AC;Kompella, UB
本研究的目的是确定结膜下施用的纳米颗粒和微粒的滞留和眼部分布。在麻醉状态下，通过结膜下注射将不同尺寸（20 nm、200 nm和2 μ m; Fluospheres，剂量400 μ g）的荧光聚苯乙烯颗粒（羧酸盐改性，带负电荷）给予雄性Sprague-Dawley大鼠。通过使用液体提取定量颗粒量，然后进行荧光分光光度分析，研究颗粒在眼周和眼组织中的分布长达60天。用40 μ g剂量的颗粒研究了剂量对颗粒分布的影响。在给药后1天评价了20和200 nm颗粒的表面疏水性增加的影响。眼周给药后，对于羧酸盐修饰的微粒以及纳米颗粒，渗透到眼组织中是可忽略的。在给药后60天，几乎全部剂量的200 nm和2 μ m颗粒保留在眼周组织中。20 nm颗粒从眼周组织中迅速消失，1天和7天后分别剩余15%和8%的给药剂量。给药后60天，在眼周组织中未检测到20 nm颗粒。在第1天结束时，表面疏水性的增加不影响200 nm颗粒的眼周滞留，但提高了20 nm颗粒的眼周滞留。得出的结论是，结膜下给药的200 nm和更大的颗粒可以几乎完全保留在给药部位至少两个月。这种大小的颗粒系统的眼周给药可能用作持续药物递送系统。
The purpose of this study was to determine the retention and ocular distribution of subconjunctivally administered nanoparticles and microparticles. Fluorescent polystyrene particles (carboxylate modified, negatively charged) of various sizes (20nm, 200nm and 2 mu m; Fluospheres, dose 400 mu g) were administered to male Sprague-Dawley rats by subconjunctival injection under anaesthesia. The disposition of the particles in the periocular and ocular tissues was studied for up to 60 days by quantifying the particle amounts using liquid extraction followed by spectrofluorimetric analysis. The effect of dose on the particle disposition was investigated with a 40-mu g dose of the particles. The effect of an increase in surface hydrophobicity was evaluated for the 20 and 200 nm particles at 1 day post administration. Following periocular administration, penetration into the ocular tissues was negligible for the carboxylate-modified microparticles as well as nanoparticles. Almost the entire dose of the 200 nm and 2 pm particles was retained in the periocular tissue at 60 days post-administration. The 20 nm particles disappeared rapidly from the periocular tissue with 15 and 8% of administered dose remaining after 1 and 7 days, respectively. The 20nm particles could not be detected in the periocular tissue at 60-days post-administration. An increase in the surface hydrophobicity did not affect the periocular retention of 200 nm particles but elevated that of the 20 nm particles, at the end of day 1. It was concluded that subconjunctivally administered 200nm and larger particles can be almost completely retained at the site of administration for at least two months. Periocular administration of particulate systems of this size would likely be useful as sustained drug delivery systems.