A biodegradable poly(lactic-co-glycolic acid) loading atorvastatin calcium(AC) nanoparticles(AC-PLGA-NPs) were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of A...A biodegradable poly(lactic-co-glycolic acid) loading atorvastatin calcium(AC) nanoparticles(AC-PLGA-NPs) were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGANPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.展开更多
Preformed albumin corona of albumin-nonselective nanoparticles(NPs)is widely exploited to inhibit the unavoidable protein adsorption upon intravenous administration.However,very few studies have concerned the preforme...Preformed albumin corona of albumin-nonselective nanoparticles(NPs)is widely exploited to inhibit the unavoidable protein adsorption upon intravenous administration.However,very few studies have concerned the preformed albumin corona of albumin-selective NPs.Herein,we report a novel type of albumin-selective NPs by decorating 6-maleimidocaproyl polyethylene glycol stearate(SA)onto PLGA NPs(SP NPs)surface,taking albuminnonselective PLGA NPs as control.PLGA NPs and SP NPs were prepared by emulsion-solvent evaporation method and the resultant NPs were in spherical shape with an average diameter around 180 nm.The corresponding albumin-coating PLGA NPs(PLGA@BSA NPs)and albumin-coating SP NPs(SP@BSA NPs)were formulated by incubating SP NPs or PLGA NPs with bovine serum albumin solution,respectively.The impact of albumin corona on particle characteristics,stability,photothermal effect,cytotoxicity,cell uptake,spheroid penetration and pharmacokinetics was investigated.In line with previous findings of preformed albumin coating,PLGA@BSA NPs exhibited higher stability,cytotoxicity,cell internalization and spheroid penetration performances in vitro,and longer blood circulation time in vivo than those of albumin-nonselective PLGA NPs,but albumin-selective SP NPs is capable of achieving a comparable in vitro and in vivo performances with both SP@BSA NPs and PLGA@BSA NPs.Our results demonstrate that SA decorated albumin-selective NPs pave a versatile avenue for optimizing nanoparticulate delivery without preformed albumin corona.展开更多
Recent work regarding the Layer by Layer （LbL） engineering of poly（lactide-co-glycolide） nanoparticles （PLGA NPs） is reviewed here. The LbL engineering of PLGA NPs is applied as a means of generating advanced dr...Recent work regarding the Layer by Layer （LbL） engineering of poly（lactide-co-glycolide） nanoparticles （PLGA NPs） is reviewed here. The LbL engineering of PLGA NPs is applied as a means of generating advanced drug delivery devices with tailored recognition, protection, cargo and release properties. LbL in combination with covalent chemistry is used to attach PEG and folic acid to control cell uptake and direct it towards cancer cells. LbL coatings composed of chitosan and alginate show low protein interactions and can be used as an alternative to Pegylation. The assembly on top of LbL coatings of lipid layers composed of variable percentages of 1,2-dioleoyl-sn-glycero-3-choline （DOPC） and 1,2-dioleoyl-sn-glycero-3-phospho- L-serine （DOPS） increases NP uptake and directs the NPs towards the endoplasmic reticulum. The antibody anti-TNF-ct is encapsulated forming a complex with alginate that is assembled LbL on top of PLGA NPs. The antibody is released in cell culture following first order kinetics. The release kinetics of encapsulated molecules inside PLGA NPs are studied when the PLGA NPs are coated via LbL with different polyelectrolytes. The intracellular release of encapsulated Doxorubicin is studied in the HepG2 cell line by means of Fluorescence Lifetime Imaging.展开更多
基金financially supported by the Science and Technology Research Project of Liaoning Provincial Education Department L2013390
文摘A biodegradable poly(lactic-co-glycolic acid) loading atorvastatin calcium(AC) nanoparticles(AC-PLGA-NPs) were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGANPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.
基金financially supported by the National Basic Research Program of China(973 Program,No.2015CB932100)National Natural Science Foundation of China(No.81703451,81573371,81473164)。
文摘Preformed albumin corona of albumin-nonselective nanoparticles(NPs)is widely exploited to inhibit the unavoidable protein adsorption upon intravenous administration.However,very few studies have concerned the preformed albumin corona of albumin-selective NPs.Herein,we report a novel type of albumin-selective NPs by decorating 6-maleimidocaproyl polyethylene glycol stearate(SA)onto PLGA NPs(SP NPs)surface,taking albuminnonselective PLGA NPs as control.PLGA NPs and SP NPs were prepared by emulsion-solvent evaporation method and the resultant NPs were in spherical shape with an average diameter around 180 nm.The corresponding albumin-coating PLGA NPs(PLGA@BSA NPs)and albumin-coating SP NPs(SP@BSA NPs)were formulated by incubating SP NPs or PLGA NPs with bovine serum albumin solution,respectively.The impact of albumin corona on particle characteristics,stability,photothermal effect,cytotoxicity,cell uptake,spheroid penetration and pharmacokinetics was investigated.In line with previous findings of preformed albumin coating,PLGA@BSA NPs exhibited higher stability,cytotoxicity,cell internalization and spheroid penetration performances in vitro,and longer blood circulation time in vivo than those of albumin-nonselective PLGA NPs,but albumin-selective SP NPs is capable of achieving a comparable in vitro and in vivo performances with both SP@BSA NPs and PLGA@BSA NPs.Our results demonstrate that SA decorated albumin-selective NPs pave a versatile avenue for optimizing nanoparticulate delivery without preformed albumin corona.
基金funded by the Spanish Ministry of Science and Innovation(MAT2010-18995)the Marie Curie project "Transport Studies on Polymer Based Nanodevices and Assemblies for Delivery and Sensing"(TRASNADE) (- FP7 People International Research Staff Exchange Scheme Grant reference:247656)the Marie Curie Project "Design of Novel Polyelectrolyte Multilayer Based Delivery Systems for Therapeutic Antibodies and siRNA" (DeSIRNA) (FP7-People IAPP Grant reference 251646)
文摘Recent work regarding the Layer by Layer （LbL） engineering of poly（lactide-co-glycolide） nanoparticles （PLGA NPs） is reviewed here. The LbL engineering of PLGA NPs is applied as a means of generating advanced drug delivery devices with tailored recognition, protection, cargo and release properties. LbL in combination with covalent chemistry is used to attach PEG and folic acid to control cell uptake and direct it towards cancer cells. LbL coatings composed of chitosan and alginate show low protein interactions and can be used as an alternative to Pegylation. The assembly on top of LbL coatings of lipid layers composed of variable percentages of 1,2-dioleoyl-sn-glycero-3-choline （DOPC） and 1,2-dioleoyl-sn-glycero-3-phospho- L-serine （DOPS） increases NP uptake and directs the NPs towards the endoplasmic reticulum. The antibody anti-TNF-ct is encapsulated forming a complex with alginate that is assembled LbL on top of PLGA NPs. The antibody is released in cell culture following first order kinetics. The release kinetics of encapsulated molecules inside PLGA NPs are studied when the PLGA NPs are coated via LbL with different polyelectrolytes. The intracellular release of encapsulated Doxorubicin is studied in the HepG2 cell line by means of Fluorescence Lifetime Imaging.
