Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento 35, I-56126 Pisa, Italy.
Int J Pharm. 2010 Aug 16;395(1-2):122-31. doi: 10.1016/j.ijpharm.2010.05.031. Epub 2010 May 24.
An interaction between tamarind seed polysaccharide (TSP) and hyaluronic acid (HA) in aqueous solution has been ascertained. Various TSP/HA mixtures have been studied as the basis for the development of a potential excipient for eye drops synergistically improved over those of the separate polymers. Information about the nature of interpolymer interactions, and their dependence on TSP/HA ratios were obtained by NMR spectroscopy in solution. Superior mucin affinity of TSP/HA mixtures with respect to the single polysaccharides was assessed by NMR proton selective relaxation rate measurements. The mucoadhesivity of the TSP/HA (3/2) mixture, evaluated in vitro by NMR or viscometry, and in vivo by its mean and maximum residence time in rabbit precorneal area, is stronger than that of the component polysaccharides or the TSP/HA mixtures of different composition. TSP/HA (3/2) is little viscous and well tolerated by rabbit eyes. It stabilizes the tear film, thereby prolonging the residence of ketotifen fumarate and diclofenac sodium in tear fluid, but is unable to permeabilize the cornea. In conclusion, mucoadhesivity is responsible for the TSP/HA (3/2) synergistic enhancement of either extra- or intra-ocular drug bioavailability.
已确定罗望子多糖（TSP）和透明质酸（HA）在水溶液中的相互作用。已经研究了各种 TSP/HA 混合物，作为潜在滴眼剂赋形剂的基础，其协同作用优于单独聚合物。通过溶液中的 NMR 光谱获得了有关聚合物间相互作用的性质及其对 TSP/HA 比例依赖性的信息。通过 NMR 质子选择性弛豫率测量评估了 TSP/HA 混合物相对于单一组分多糖的更高粘蛋白亲和力。通过 NMR 或粘度计体外评估以及通过其在兔角膜前区的平均和最大停留时间的体内评估，TSP/HA（3/2）混合物的粘膜粘附性强于组成多糖或不同组成的 TSP/HA 混合物。TSP/HA（3/2）的粘性较小，兔子眼睛耐受良好。它稳定泪膜，从而延长富马酸酮替芬和双氯芬酸钠在泪液中的停留时间，但不能使角膜渗透。总之，粘膜粘附性是 TSP/HA（3/2）协同增强眼外或眼内药物生物利用度的原因。
