喃氟啶从Poloxamer407凝胶基质中的体外释放

目的:观察Poloxamer 407凝胶的形成及液体/凝胶互相转化的条件和喃氟啶在该凝胶中的体外释放.方法:以磷酸盐缓冲液[pH(7.40±0.01)作为Poloxamer 407的稀释剂,以喃氟啶作为实验药物做体外溶出.结果:Poloxmer 407的浓度在15%～40%之内时,随着温度从0℃上升到37℃,其混合物从液体迅速转化成凝胶.相变温度随着Poloxamer407的浓度升高而降低.喃氟啶在该凝胶中的体外释放为零级释放,且随Poloxamer 407浓度的增加,释放速度变慢.8h时.含Poloxamer 407分别为20%,25%,30%,35%(m/m)的凝胶中时喃氟啶的累积释放率分别是(98.22±0.12)%,(86.20±0.20)%,(68.25±0.14)%,(50.02±0.08)%.结论:鉴于Poloxamr 407所具有的特殊的逆温相变性质,作为血管外注射型缓释植入剂的载体是有前途的.

尼古丁二元醇脂质体温敏凝胶的制备及体外评价

目的 制备尼古丁二元醇脂质体温敏凝胶,并对其进行处方筛选,优化药物的经皮转运。方法 选用温敏材料泊洛沙姆407(P407)及泊洛沙姆188(P188)为基质,尼古丁二元醇脂质体温敏凝胶用冷溶法制备,以胶凝温度为考察指标,采用单因素实验对尼古丁二元醇脂质体温敏凝胶进行处方优化;考察尼古丁乙醇溶液、二元醇脂质体及含P407/P188二元醇脂质体温敏凝胶的体外释放性质;Franz扩散池对比尼古丁二元醇脂质体和二元醇脂质体凝胶透皮量及皮内滞留量。结果 制备的温敏凝胶在室温以液体状态存在,在32℃形成凝胶。体外释放实验显示,24 h二元醇脂质体和二元醇脂质体凝胶的释放率分别是(78.60%±0.43%)、(56.36%±0.26%)。与二元醇脂质体相比,二元醇脂质体凝胶有明显的缓释作用。12 h透皮实验表明,二元醇脂质体凝胶可以增大皮内滞留量,而二元醇脂质体可以增加透皮深度。结论 与二元醇脂质体相比,二元醇脂质体温敏凝胶有明显的缓释作用,且显著增加药物的皮内滞留量。

瑞舒伐他汀对poloxamer407诱导的小鼠高血脂模型血脂水平的影响

目的观察瑞舒伐他汀对poloxamer 407(P-407)诱导的小鼠高血脂模型血脂水平的影响。方法小鼠于腹腔注射P-407前先以瑞舒伐他汀(2或10 mg/kg)连续灌胃,并于腹腔注射P-407(0.3 g/kg)后3 h再次灌胃瑞舒伐他汀。以注射P-407前及注射后第3、4、24及48 h血甘油三酯和胆固醇水平评价瑞舒伐他汀的疗效,同时观察造模后24 h高密度脂蛋白-胆固醇水平。结果瑞舒伐他汀组血清甘油三酯和胆固醇水平减低,具有显著的量效关系,且作用可持续至造模后的48 h。瑞舒伐他汀组小鼠造模后24 h血清高密度脂蛋白-胆固醇水平显著升高(P<0.05)。结论瑞舒伐他汀可有效降低P-407诱导的高血脂模型小鼠的血脂水平。

Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties:preparation, characterization and application in a vaginal drug delivery system

Lack of mucoadhesive properties is the major drawback to poloxamer 407(F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an aminofunctionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407(F127-NH2) 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-NH2-based in situ hydrogels(NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin wasrevealed 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. Ex vivo and in vivo fluorescence 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-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.

A novel rat model of fatty organ degeneration induced by poloxamer 407

Traditional methods of inducing hyperlipidemia in animal models are either costly(genetic manipulation)or it is difficult to control for the effects of other variables.For example,during high-fat feeding,the amount of high-fat diet intake per animal cannot be precisely controlled.The aim of this study was to develop an experimental model of fatty organ degeneration induced by poloxamer 407(P-407).The study was conducted in 2-month-old,male Sprague-Dawley rats that were administered intraperitoneally with either 10%(w/w)P-407(1 g/kg)or saline(10 mL/kg)for 4 months.Their lipid profile,organ degeneration due to fat deposition,and body mass were assessed.Intraperitoneal administration of P-407 resulted in significant increases in plasma triglycerides(P
0.001),total cholesterol(P<0.001),high-density lipoprotein-cholesterol(P
0.001),and low-density lipoprotein(P<0.001)cholesterol.In contrast to the control group,fatty tissue degeneration was observed in the liver,spleen,and kidneys of P-407-treated rats.Positive correlations between fatty tissue degeneration,and the atherogenic index of plasma(P<0.001)and the ratio of total cholesterol to high-density-lipoprotein(P<0.001)were identified.In addition,treatment with P-407 for 3 to 4 months caused a significant reduction in body mass relative to controls(P<0.001).Thus,this study describes the development of a cost-effective experimental rat model of organ degeneration,characterized by fat accumulation in the liver,spleen,and kidneys,which could be used for the study of steatosis and related diseases arising from sustained untreated dyslipidemia.Furthermore,both the atherogenic index of plasma and the ratio of total cholesterol to high-density lipoprotein-cholesterol can be used to predict the risk of fatty tissue degeneration in this model.The study was approval of the University of Jishou Biomedical Research Ethics Committee,China.

Enhanced bioavailability and biosafety of cannabidiol nanomicelles for effective anti-inflammatory therapy

Cannabidiol(CBD)shows great anti-inflammatory potential;however,the hydrophobicity and strong first-pass effect of CBD leads to its extremely low oral bioavailability.Poloxamer 407(P407)is a tri-block copolymer composed of(poly)ethylene oxide(PEO)and(poly)propylene oxide(PPO)sections.It has a PEO-PPO-PEO structure,which is widely used in the preparation of drug delivery systems that are highly biocompatible.When it reaches a certain concentration in water,P407 can self-assemble into a micelle structure containing a hydrophobic core and a hydrophilic shell.A potential approach to enhanc-ing the oral bioavailability of hydrophobic drugs incorporating them into the hydrophilic carrier.We prepared CBD nanomicelles with a drug loading of 14.29%by a cosolvent evaporation method using P407 with appropriate antioxidants.Cell experiments indicated that anti-inflammatory markers(IL-4 and IL-10)increased,while inflammatory markers(TNF-αand IL-6)decreased.Moreover,animal experiments showed that inflammatory cells were inhibited by CBD nanomicelles,and the anti-inflammatory effect of micelles was better than that of CBD,while no obvious evidence indicated toxicity to the liver and kidney.

Genistein-loaded poloxamer 403/407 mixed micelles: preparation and pharmacokinetic study in rats

In the present study, we aimed to prepare poloxamer 403/407 mixed micelles in order to improve the solubility and oral bioavailability of genistein. Genistein was incorporated in the mixed poloxamer micelles by thin-film hydration method, and its physicochemical properties, including particle size, zeta potential, entrapment efficiency and drug loading, were investigated. In vitro release of genistein from the mixed micelles was monitored by dialysis method, and pharmacokinetic study of genistein loaded mixed micelles was carried out in rats. We found that the particle size and zeta potential of mixed micelles were（20.31±0.43） nm and（–8.94±0.35） m V, with encapsulation efficiency 90.59%±0.67% and drug loading 7.74%±0.05%. Solubility of genistein in mixed micelles reached 3.80 mg/m L, which was about 130 times higher than that in water. Genistein-loaded mixed micelles showed sustained release characteristics in vitro with no burst release phenomenon, but it was faster than suspension. The AUC0–t and AUC0–∞ of mixed micelles were 196.74% and 204.62% greater than that of genisein suspension, respectively. Consequently, poloxamer 403/407 mixed micelles significantly improved the solubility and oral bioavailability of genistein, which could be used as an effective drug delivery system for oral administration of poorly soluble drugs.