The objectives of the present study were to prepare stealthy etoposide proliposomes and study the pharmacokinetics in rabbits. Blank stealthy liposomes were prepared by film dispersion method. Stealthy etoposide lipos...The objectives of the present study were to prepare stealthy etoposide proliposomes and study the pharmacokinetics in rabbits. Blank stealthy liposomes were prepared by film dispersion method. Stealthy etoposide liposomes were prepared by using the ammonium sulfate gradient loading procedure. Vacuum freeze-drying technique was used to dry stealthy etoposide liposomes. Encapsulation efficiency of stealthy etoposide proliposomes was determined by Sephadex chromatography. The morphology was observed by transmission electronic microscope. The particle size and zeta potential were measured by using electrophoretic light scattering technology. The pharmacokinetics in rabbits was evaluated by comparison with etoposide injection and conventional liposomes, respectively. Mean encapsulation efficiency of stealthy etoposide proliposomes was 83.92% ± 3.65% （n = 3）. The liposomes were round or oval. Mean particle size was （124.5 ±26.9） nm, and zeta potential was （-39.50 ±1.04） mV. Following intravenous injection administration at a dose of 1.5 mg/kg etoposide, the three kinds of etoposide preparations were fitted with the two-compartment model. T1/2 β and A UC values of stealthy etoposide proliposomes were （19.26 ± 3.16） h and （26.04 ±3.53） μg/h/mL, respectively. T1/2 β and AUC values of etoposide injection were （0.94 ± 0.21） h and （0.98 ± 0.26） μg/h/mL, respectively. T1/2β and AUC values of conventional liposomes were （7.99 ± 1.36） h and （11.65 ± 1.70） μg/h/mL, respectively. Results indicated that the stealthy etoposide proliposomes could significantly extend the duration of etoposide in blood circulation.展开更多
[Objectives]To effectively solve the problem of poor oral bioavailability of total flavonoids in Kang Zhu Gan Lu(ZYZH),a new hypoglycemic Tibetan solid preparation,ZYZH oral proliposome was prepared by modern preparat...[Objectives]To effectively solve the problem of poor oral bioavailability of total flavonoids in Kang Zhu Gan Lu(ZYZH),a new hypoglycemic Tibetan solid preparation,ZYZH oral proliposome was prepared by modern preparation method,and its hypoglycemic effect was evaluated.[Methods]ZYZH proliposome was prepared by carrier deposition method,and its particle morphology and Zeta potential were detected.Taking encapsulation efficacy as indictor,the optimal prescription and preparation process of ZYZH oral proliposome were screened by orthogonal experiment.In addition,the hypoglycemic activity of ZYZH oral liposome in alloxan-induced hyperglycemic mice was studied.[Results]The repose angle,average particle size,encapsulation efficiency,and Zeta potential of ZYZH proliposome are 34.2°,(442.5±3.5)nm,67.7%and(-47.2±3.4)mV,respectively.Compared with the model group,the fasting blood glucose level of the hyperglycemic mice significantly declined(P<0.01),and their body weight changed insignificantly after four weeks of oral administration of ZYZH proliposome(P>0.05).[Conclusions]The preparation process of ZYZH oral proliposome is characterized by simple operation,high encapsulation efficiency and good stability.The new hypoglycemic Tibetan drug ZYZH oral liposome has obvious hypoglycemic effect on alloxan-induced hyperglycemic mice.展开更多
The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures i...The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve ef fi cacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies.This review covers the recent advances in the fi eld of insoluble drug delivery and business prospects.展开更多
基金Research Projects of Heilongjiang Science and Technology Department (Grant No.GC05C31601).
文摘The objectives of the present study were to prepare stealthy etoposide proliposomes and study the pharmacokinetics in rabbits. Blank stealthy liposomes were prepared by film dispersion method. Stealthy etoposide liposomes were prepared by using the ammonium sulfate gradient loading procedure. Vacuum freeze-drying technique was used to dry stealthy etoposide liposomes. Encapsulation efficiency of stealthy etoposide proliposomes was determined by Sephadex chromatography. The morphology was observed by transmission electronic microscope. The particle size and zeta potential were measured by using electrophoretic light scattering technology. The pharmacokinetics in rabbits was evaluated by comparison with etoposide injection and conventional liposomes, respectively. Mean encapsulation efficiency of stealthy etoposide proliposomes was 83.92% ± 3.65% （n = 3）. The liposomes were round or oval. Mean particle size was （124.5 ±26.9） nm, and zeta potential was （-39.50 ±1.04） mV. Following intravenous injection administration at a dose of 1.5 mg/kg etoposide, the three kinds of etoposide preparations were fitted with the two-compartment model. T1/2 β and A UC values of stealthy etoposide proliposomes were （19.26 ± 3.16） h and （26.04 ±3.53） μg/h/mL, respectively. T1/2 β and AUC values of etoposide injection were （0.94 ± 0.21） h and （0.98 ± 0.26） μg/h/mL, respectively. T1/2β and AUC values of conventional liposomes were （7.99 ± 1.36） h and （11.65 ± 1.70） μg/h/mL, respectively. Results indicated that the stealthy etoposide proliposomes could significantly extend the duration of etoposide in blood circulation.
基金Supported by Integration and industrialization demonstration of comprehensive utilization and development of the unique ecological Malus torangoades(Rehd.)Hughes in the Qinghai-Tibet Plateau(Guo Ke Fa Nong[2012]745)
文摘[Objectives]To effectively solve the problem of poor oral bioavailability of total flavonoids in Kang Zhu Gan Lu(ZYZH),a new hypoglycemic Tibetan solid preparation,ZYZH oral proliposome was prepared by modern preparation method,and its hypoglycemic effect was evaluated.[Methods]ZYZH proliposome was prepared by carrier deposition method,and its particle morphology and Zeta potential were detected.Taking encapsulation efficacy as indictor,the optimal prescription and preparation process of ZYZH oral proliposome were screened by orthogonal experiment.In addition,the hypoglycemic activity of ZYZH oral liposome in alloxan-induced hyperglycemic mice was studied.[Results]The repose angle,average particle size,encapsulation efficiency,and Zeta potential of ZYZH proliposome are 34.2°,(442.5±3.5)nm,67.7%and(-47.2±3.4)mV,respectively.Compared with the model group,the fasting blood glucose level of the hyperglycemic mice significantly declined(P<0.01),and their body weight changed insignificantly after four weeks of oral administration of ZYZH proliposome(P>0.05).[Conclusions]The preparation process of ZYZH oral proliposome is characterized by simple operation,high encapsulation efficiency and good stability.The new hypoglycemic Tibetan drug ZYZH oral liposome has obvious hypoglycemic effect on alloxan-induced hyperglycemic mice.
文摘The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve ef fi cacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies.This review covers the recent advances in the fi eld of insoluble drug delivery and business prospects.
