Sandri Giuseppina, Rossi Silvia, Bonferoni Maria Cristina, Ferrari Franca, Zambito Ylenia, Di Colo Giacomo, Caramella Carla
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Pavia, V.le Taramelli 12, 27100 Pavia, Italy.
Int J Pharm. 2005 Jun 13;297(1-2):146-55. doi: 10.1016/j.ijpharm.2005.03.017.
The aim was to evaluate the influence of the degree of quaternization of N-trimethyl chitosans (TMCs) on the mucoadhesive and penetration enhancement properties towards buccal mucosa. Fluorescein isothiocyanate dextran (MW 4400 Da) (FD4) was used as model molecule. TMCs, obtained from chitosans of different MW (1460 and 580 kDa, respectively), were hydrated in distilled water and in pH 6.4 phosphate buffer (simulating the buccal fluid). The polymer solutions were subjected to mucoadhesion measurements towards bovine submaxillary mucin dispersion and porcine buccal mucosa and to FD4 permeation tests through porcine cheek epithelium. The trimethylation of chitosan allows maintenance or improvement of the mucoadhesive properties of the starting chitosans dependently on quaternization degree. In particular, the mucoadhesive properties increase on increasing degree of quaternization. The trimethylation does not produce any change in chitosan penetration enhancement properties when the medium is distilled water while if pH 6.4 buffer is used, the trimethylation produces an improvement in chitosan penetration enhancing effect. TMC derived from the lower MW chitosan and characterized by the highest degree of quaternization shows the best mucoadhesive and penetration enhancement properties and is the most promising TMC to improve the bioavailability of hydrophilic and large MW molecules (like peptides and proteins) when administered via buccal route.
目的是评估N-三甲基壳聚糖（TMCs）的季铵化程度对颊黏膜的黏附性和渗透促进性能的影响。异硫氰酸荧光素葡聚糖（分子量4400 Da）（FD4）用作模型分子。分别由不同分子量（1460和580 kDa）的壳聚糖制得的TMCs在蒸馏水和pH 6.4的磷酸盐缓冲液（模拟颊液）中进行水合。聚合物溶液对牛颌下黏蛋白分散体和猪颊黏膜进行黏附性测量，并通过猪颊上皮进行FD4渗透试验。壳聚糖的三甲基化可根据季铵化程度维持或改善起始壳聚糖的黏附性能。特别是，黏附性能随季铵化程度的增加而增加。当介质为蒸馏水时，三甲基化不会对壳聚糖的渗透促进性能产生任何变化，而如果使用pH 6.4缓冲液，三甲基化会提高壳聚糖的渗透促进效果。由较低分子量壳聚糖衍生且具有最高季铵化程度的TMC表现出最佳的黏附性和渗透促进性能，是通过颊部途径给药时提高亲水性和大分子（如肽和蛋白质）生物利用度最有前景的TMC。
