INFLUENCE OF MOLECULAR-WEIGHT AND FORMULATION PH ON THE PRECORNEAL CLEARANCE RATE OF HYALURONIC-ACID IN THE RABBIT EYE
INFLUENCE OF MOLECULAR-WEIGHT AND FORMULATION PH ON THE PRECORNEAL CLEARANCE RATE OF HYALURONIC-ACID IN THE RABBIT EYE
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DOI：
10.1016/0378-5173(94)00389-m
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发表时间：
1995-05-16
影响因子：
5.8
通讯作者：
KELLAWAY, IW
中科院分区：
文献类型：
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作者：
DURRANI, AM;FARR, SJ;KELLAWAY, IW
透明质酸是一种天然聚合物，由于其保水能力，可与细胞膜结合，因此可被视为控制眼部给药的推定载体。在体外粘膜粘附试验中，与低分子量透明质酸相比，Healon（R）（HA-Na）的分离力显著更大。此外，在pH 5下的这种生物粘附性比在pH 7.4下的生物粘附性更强。采用In-111标记的生物聚合物的γ射线照相成像，研究了pH 5.0和7.4时透明质酸钠（0.2%）的角膜前清除率。大分子的质子化没有导致眼粘膜粘附的任何增加，因为在pH 5.0下的平均停留时间并不显著长于pH 7.4下的平均停留时间。同时考察了透明质酸分子量对角膜滞留的影响。对于Healon（R）（Mol. Wt2.2 × 10（6））与两种较低分子量透明质酸样品（Mel. Wt 134 000和620 000）。
Hyaluronic acid is a natural polymer which, due to its water retaining capability, binds to cell membranes and can therefore be considered as a putative vehicle for controlled ocular delivery. In an in vitro mucoadhesion test, the force of detachment was significantly greater for Healon(R) (HA-Na) compared to low molecular weight hyaluronic acid. Also, this bioadhesion was stronger for Healon(R) at pH 5 than at pH 7.4. The precorneal clearance of sodium hyaluronate (0.2%) was investigated at pH 5.0 and 7.4 by employing gamma scintigraphic imaging of the In-111-labelled biopolymer. Protonation of the macromolecule did not result in any increase in ocular mucoadhesion as the mean residence time at pH 5.0 was not significantly longer than at pH 7.4. The effect of molecular weight of hyaluronic acid on the corneal retention was also investigated. There was a statistically significant difference (p < 0.05) in the clearance half-life (t(0.5)) and AUC of % activity remaining vs time plot for Healon(R) (Mol. Wt 2.2 x 10(6)) compared to those observed for the two lower molecular weight hyaluronic acid samples (Mel. Wt 134 000 and 620 000).