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 thermosensi...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.展开更多
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...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(P0.001),total cholesterol(P<0.001),high-density lipoprotein-cholesterol(P0.001),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.展开更多
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 compos...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.展开更多
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-f...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.展开更多
基金Financial support from the China Natural Science Foundation(NSFC: 81573361 and 81102385)
文摘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.
基金partly supported by grants from Jishou University(No.jsdxrcyjkyxm201304 to MY and No.Jdy1828 to JL).
文摘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(P0.001),total cholesterol(P<0.001),high-density lipoprotein-cholesterol(P0.001),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.
基金supports from the National Key Research and Development Program of China(grant No.2021YFE0103500)National Natural Science Foundation of China(grant No.52003021).
文摘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.
基金The Zhejiang Public Welfare Technology Application Research Project(Grant No.2015C31100)the Ningbo Science and Technology Innovation Team Project(Grant No.2015C110027)
文摘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.
