Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, UNITEFA-CONICET, Córdoba, Argentina.
J Ocul Pharmacol Ther. 2012 Apr;28(2):102-9. doi: 10.1089/jop.2011.0104. Epub 2011 Nov 7.
To evaluate the performance of 6-O-Lauryl-l-ascorbic acid nanostructures (coagels) as vehicles for acetazolamide (AZM) in ophthalmic administration by in vitro and in vivo experimental tests.
The systems of coagel + AZM were evaluated in terms of their in vitro release (dialysis membrane), permeability (isolated cornea), pharmacological effectiveness [intraocular pressure (IOP)-reduction in normotensive rabbits], and potential irritant effects.
The results concerning AZM permeation were better when vehiculized in coagels compared with ringer solution, which was evident from the AZM steady-state flux and P(app) values (J=1.43 μg/min and P(app)=3.04 cm.s(1)). As a consequence of this increase in permeation, the coagel-AZMs were more effective in lowering the IOP, according to the results obtained from the in vivo assays. Coagels loaded with 0.4% (W/W) of AZM showed a higher hypotensive effect in rabbits compared with the commercial formulation AZOPT(®) (brinzolamide 1%), mainly due to the prolonged effect of the former. In all cases, the intensity of irritation was time dependent. The sodium lauryl sulphate solution (2%) used as a positive control produced serious injury 30 min postadministration. This effect caused irritation, which decreased slowly and even at 180 min, the discomfort was still considerable. However, in the case of coagels, a mild-to-moderate effect was observed.
The incorporation of AZM in coagels seems to improve the ocular bioavailability of this drug. Coagel-AZM 0.4% showed a higher hypotensive effect, with a mild-to-moderate irritant effect. These systems could be administrated in human beings, although more detailed studies still need to be carried out.
通过体外和体内实验评估 6-O-月桂酰基-L-抗坏血酸纳米结构（凝结胶）作为眼部给予乙酰唑胺（AZM）的载体的性能。
从体外释放（透析膜）、渗透性（分离角膜）、药理学功效[正常眼压兔的眼压（IOP）降低]和潜在刺激性等方面评估了凝结胶+AZM 体系。
与林格溶液相比，将 AZM 包封在凝结胶中时，其渗透结果更好，这从 AZM 的稳态通量和 P(app)值（J=1.43μg/min 和 P(app)=3.04cm·s-1）中可以明显看出。由于渗透增加，根据体内试验结果，凝结胶-AZM 降低 IOP 的效果更好。与市售制剂 AZOPT（®）（布林佐胺 1%）相比，负载 0.4%（W/W）AZM 的凝结胶在兔子中显示出更高的降压效果，主要是由于前者的作用时间延长。在所有情况下，刺激强度都是时间依赖性的。作为阳性对照的 2%十二烷基硫酸钠溶液在给药后 30 分钟引起严重损伤。这种效应引起刺激，其缓慢减弱，甚至在 180 分钟时，不适感仍然相当大。然而，在凝结胶的情况下，观察到轻度至中度的效果。
将 AZM 包封在凝结胶中似乎可以提高该药物的眼部生物利用度。凝结胶-AZM 0.4%显示出更高的降压效果，具有轻度至中度刺激性。这些系统可以在人体中使用，尽管仍需要进行更详细的研究。
