ABSTRACT
Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127)-basedhydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitivehydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG) as model drug, AG-loaded F127-NH-basedhydrogels (NFGs) were evaluated with respect to rheology, drug release,vaginal mucosal adhesion,intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NHis capable of forming a thermosensitivehydrogel with sustained drug release properties. An interaction between positively charged F127-NHand negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin.andfluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-basedhydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.
ABSTRACT
Objective To investigate the effect of exercise preconditioning on the expression of nerve growth factor(NGF) and its receptor TrkA as well as learning-and-memory abilities in rats suffered from focal cerebral ischemia.Methods Thirty-six male SD rats were randomly divided into sham operation group (Sham-MCAO,n=12),focal cerebral ischemia-reperfusion group (MCAO,n=12) and exercise preconditioning + cerebral ischemia-reperfusion group (EX+MCAO,n=12).Rats in EX+MCAO group were placed in the treadmill device and accepted 4 weeks exercise training.Then method of middle cerebral artery occlusion was applied to prepare transient focal cerebral ischemia reperfusion model.Garcia's method was used to assess the neural function in rats.Western blotting was applied to test the expression of NGF and TrkA protein in the successfully established experimental MCAO rats.Morris water maze experiment was uti lized to test the learning-and-memory abilities of the rats.Results (1) Compared with Sham-MCAO group,the expression of NGF in rats' brain tissue was lower in MCAO group (cerebral ischemia 1h reperfusion 24h) (P＜0.05).The expression of NGF of EX+MCAO group was higher than that of MCAO group,but still lower than that of Sham-MCAO group (P＜0.05).(2)The expression of TrkA in rats' brain tissue was higher in MCAO group compared with Sham-MCAO group (P＜0.05).Compared with MCAO group,the expression of TrkA was even higher in EX+MCAO group (P＜0.05).(3)On the fifth day in the Morris water maze test,the latency of MCAO group was significantly longer than that of Sham-MCAO group((9.36± 1.18)s vs (4.86± 1.52) s,P＜0.05).However,compared with MCAO group,the latency in EX+MCAO group ((6.02± 1.04) s) was shorter,but still longer than Sham-MCAO group (P＜0.05).There was no significant difference among the three groups in the average swimming speed (P＞0.05).Conclusion Exercise preconditioning can up-regulate the expressions of NGF and TrkA protein,which can also improve the learning-and-memory abilities in rats suffered from focal cerebral ischemia reperfusion injury.