Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago,its anti-cancer properties for various malignancies have been under intense investigation.However,the c...Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago,its anti-cancer properties for various malignancies have been under intense investigation.However,the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers.This is due to arsenic's rapid clearance by the body's immune system before reaching the tumor site.Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success.This review summarizes the past and current utilization of arsenic trioxide in the medical field with primary focus on the implementation of nanotechnology for arsenic trioxide delivery to solid cancer cells.Different approaches that have been employed to increase arsenic's efficacy,specificity and bioavailability to solid cancer cells were evaluated and compared.The potential of combining different approaches or tailoring delivery vehicles to target specific types of solid cancers according to individual cancer characteristics and arsenic chemistry is proposed and discussed.展开更多
Alpha-mangostin(AMG),a natural xanthone extracted from Garcinia mangostana Linn,has a variety of pharmacological therapeutic effects such as antioxidant activity,antibacterial activity,anticancer,and anti-inflammatory...Alpha-mangostin(AMG),a natural xanthone extracted from Garcinia mangostana Linn,has a variety of pharmacological therapeutic effects such as antioxidant activity,antibacterial activity,anticancer,and anti-inflammatory[1].However,it has poor aqueous-solubility and dissolution,which results in low bioavailability.Solid self-emulsifying drug delivery system(solid-SEDDS),an effective pharmaceutical strategy,offers the potential for enhancing the oral bioavailability of poorly water-soluble drugs[2].Therefore,solid-SEDDS is of interest as a potential method for enhancing the solubility and dissolution of AMG.展开更多
The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. ...The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated selfmicroemulsifying drug delivery system(S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS.Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper selfmicroemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS.Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.展开更多
This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazola...This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate.The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium.In vitro release was detected by a dialysis method in reverse.The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes.The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique.The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting.Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500.The MDZ was completely released in 10 h.A significant decrease in the formation of 1’-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed.A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250.This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.展开更多
To investigate the influence of mesopores towards the solidification of self-microemulsifying drug delivery system(SMEDDS), mesoporous silica nanospheres(MSNs) and Santa Barbara Amorphous-15(SBA-15) were compared. The...To investigate the influence of mesopores towards the solidification of self-microemulsifying drug delivery system(SMEDDS), mesoporous silica nanospheres(MSNs) and Santa Barbara Amorphous-15(SBA-15) were compared. The MSNs had hydrodynamic size of 195.35 ± 5.82 nm, and pore diameter of 2.70 nm. The SBA-15 had hydrodynamic size of 2312.19 ± 106.93 nm, and pore diameter of 10.91 nm. The MSNs and SBA-15 showed similar loading efficiency of SMEDDS containing sirolimus(SRL). However,MSNs had higher drug dissolution and in vivo absorption, with relative bioavailability of 174.62%. Thus,the length of mesopores played a more important role in solidification of SMEDDS as compared with the pore diameter. This study suggests that the SMEDDS-MSNs can be a potential candidate for oral administration of hydrophobic drugs.展开更多
This paper reviewed the study of triptolide-loaded nano delivery systems (NDOS) in our group during the past. It was investigated for the preparation, characterization, pharmacology and toxicology of solid lipid nanop...This paper reviewed the study of triptolide-loaded nano delivery systems (NDOS) in our group during the past. It was investigated for the preparation, characterization, pharmacology and toxicology of solid lipid nanoparticles (SLN), microemulsion and polymeric nanoparticles. The results indicated that the NDS presented more powerful activity and a lower toxicity in comparison with other drug carrier.展开更多
The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally s...The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally self-assembled somes or particles),including cubosomes and hexosomes,and solid lipid nanoparticles(SLNs)have unique structural features,making them attractive as nanocarriers for drug delivery.In this contribution,we focus exclusively on recent advances in formation and characterization of ISAsomes,mainly cubosomes and hexosomes,and their use as versatile nanocarriers for different drug delivery applications.Additionally,the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo.Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies,further investigations on improved understanding of the interactions of these nanoparticles with biological fuids and tissues of the target sites is necessary for effcient designing of drug nanocarriers and exploring potential clinical applications.展开更多
文摘Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago,its anti-cancer properties for various malignancies have been under intense investigation.However,the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers.This is due to arsenic's rapid clearance by the body's immune system before reaching the tumor site.Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success.This review summarizes the past and current utilization of arsenic trioxide in the medical field with primary focus on the implementation of nanotechnology for arsenic trioxide delivery to solid cancer cells.Different approaches that have been employed to increase arsenic's efficacy,specificity and bioavailability to solid cancer cells were evaluated and compared.The potential of combining different approaches or tailoring delivery vehicles to target specific types of solid cancers according to individual cancer characteristics and arsenic chemistry is proposed and discussed.
文摘Alpha-mangostin(AMG),a natural xanthone extracted from Garcinia mangostana Linn,has a variety of pharmacological therapeutic effects such as antioxidant activity,antibacterial activity,anticancer,and anti-inflammatory[1].However,it has poor aqueous-solubility and dissolution,which results in low bioavailability.Solid self-emulsifying drug delivery system(solid-SEDDS),an effective pharmaceutical strategy,offers the potential for enhancing the oral bioavailability of poorly water-soluble drugs[2].Therefore,solid-SEDDS is of interest as a potential method for enhancing the solubility and dissolution of AMG.
基金the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIP)(no.2015R1A5A1008958)supported by the Industry Technology Development Program(10077593)funded by the Ministry of Trade,Industry&Energy(MOTIE,Korea)。
文摘The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated selfmicroemulsifying drug delivery system(S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS.Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper selfmicroemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS.Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.
基金supported by a grant from National Natural Sciences Foundation of China (No.30873171)
文摘This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate.The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium.In vitro release was detected by a dialysis method in reverse.The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes.The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique.The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting.Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500.The MDZ was completely released in 10 h.A significant decrease in the formation of 1’-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed.A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250.This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.
基金supported by the Natural Science Foundation of Fujian Province(Nos.2017J01822 and 2018J01347)Fujian Medical University(No.2017XQ1202)Fuzhou General Hospital(No.2017Q06)
文摘To investigate the influence of mesopores towards the solidification of self-microemulsifying drug delivery system(SMEDDS), mesoporous silica nanospheres(MSNs) and Santa Barbara Amorphous-15(SBA-15) were compared. The MSNs had hydrodynamic size of 195.35 ± 5.82 nm, and pore diameter of 2.70 nm. The SBA-15 had hydrodynamic size of 2312.19 ± 106.93 nm, and pore diameter of 10.91 nm. The MSNs and SBA-15 showed similar loading efficiency of SMEDDS containing sirolimus(SRL). However,MSNs had higher drug dissolution and in vivo absorption, with relative bioavailability of 174.62%. Thus,the length of mesopores played a more important role in solidification of SMEDDS as compared with the pore diameter. This study suggests that the SMEDDS-MSNs can be a potential candidate for oral administration of hydrophobic drugs.
文摘This paper reviewed the study of triptolide-loaded nano delivery systems (NDOS) in our group during the past. It was investigated for the preparation, characterization, pharmacology and toxicology of solid lipid nanoparticles (SLN), microemulsion and polymeric nanoparticles. The results indicated that the NDS presented more powerful activity and a lower toxicity in comparison with other drug carrier.
基金Financial support to Anan Yaghmur for studies on development of drug nanocarriers based on cubosomes and hexosomes by the Danish Council for Independent Research|Technology and Production Sciences(references 1335-00150b and DFF-7017-00065,Denmark)。
文摘The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally self-assembled somes or particles),including cubosomes and hexosomes,and solid lipid nanoparticles(SLNs)have unique structural features,making them attractive as nanocarriers for drug delivery.In this contribution,we focus exclusively on recent advances in formation and characterization of ISAsomes,mainly cubosomes and hexosomes,and their use as versatile nanocarriers for different drug delivery applications.Additionally,the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo.Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies,further investigations on improved understanding of the interactions of these nanoparticles with biological fuids and tissues of the target sites is necessary for effcient designing of drug nanocarriers and exploring potential clinical applications.