Felt O, Furrer P, Mayer J M, Plazonnet B, Buri P, Gurny R
School of Pharmacy, University of Geneva, 30, Quai Ernest-Ansermet, CH-1211, Geneva 4, Switzerland.
Int J Pharm. 1999 Apr 15;180(2):185-93. doi: 10.1016/s0378-5173(99)00003-4.
The mucoadhesive polysaccharide chitosan was evaluated as a potential component in ophthalmic gels for enabling increased precorneal drug residence times. This cationic vehicle was expected to slow down drug elimination by the lacrymal flow both by increasing solution viscosity and by interacting with the negative charges of the mucus. The molecular weight (Mw) and concentration of polysaccharide were studied in four types of chitosan as parameters that might influence ocular tolerability and precorneal residence time of formulations containing tobramycin as therapeutic agent. An ocular irritation test, using confocal laser scanning ophthalmoscopy (CLSO) combined with corneal fluorescein staining, clearly demonstrated the excellent tolerance of chitosan after topical administration onto the corneal surface. Gamma scintigraphic data showed that the clearance of the formulations labelled with 99mTc-DTPA was significantly delayed in the presence of chitosan with respect to the commercial collyrium (Tobrex(R)), regardless of the concentration and of the molecular weight of chitosan in solution. At least a 3-fold increase of the corneal residence time was achieved in the presence of chitosan when compared to Tobrex(R).
对粘膜粘附性多糖壳聚糖进行了评估，将其作为眼用凝胶中的一种潜在成分，以延长角膜前药物停留时间。这种阳离子载体有望通过增加溶液粘度以及与粘液的负电荷相互作用，减缓泪液流动导致的药物消除。研究了四种壳聚糖的分子量（Mw）和多糖浓度，将其作为可能影响含妥布霉素作为治疗剂的制剂的眼耐受性和角膜前停留时间的参数。使用共聚焦激光扫描检眼镜（CLSO）结合角膜荧光素染色进行的眼刺激试验清楚地表明，壳聚糖局部应用于角膜表面后具有良好的耐受性。γ闪烁扫描数据显示，无论壳聚糖在溶液中的浓度和分子量如何，在壳聚糖存在下，用99mTc-DTPA标记的制剂的清除相对于市售洗眼液（托百士（R））均显著延迟。与托百士（R）相比，在壳聚糖存在下，角膜停留时间至少增加了3倍。
