ABSTRACT
Conventional liver targeted system focuses on delivering drugs to liver, bringing toxicity on hepatic normal tissues. The purpose of this study is to construct a new system capable of specially targeting to hepatic carcinoma instead of the whole liver. Based on the fact that nanoparticles (NPs) bound with either biotin or avidin tend to accumulate in tumors and avidin-attached reagents were quickly eliminated from blood circulation and assembled in liver, trans-resveratrol loaded chitosan nanoparticles (CS-NPs), CS-NPs with the surface modified either by biotin (B-CS-NPs) or by both biotin and avidin (A-B-CS-NPs) were prepared and their physiochemical properties were investigated. The in vitro release profiles of the three NPs all conformed to bioexponential equation. Pharmacokinetic experiment indicated that A-B-CS-NPs rapidly assembled in liver after injection, with the highest liver targeting index of 2.70, while the modification of biotin attenuated the liver targeting ability of NPs. Inhibitory study on HepG2 cells declared that compared to trans-resveratrol solution and CS-NPs, both B-CS-NPs and A-B-CS-NPs significantly improved the anticancer activity. When incubated with HepG2 cells at high concentration for longer time, A-B-CS-NPs exhibited superior cytotoxicity than B-CS-NPs. This study exclaims that A-B-CS-NPs may be a potent drug delivery vector specially targeting to hepatic carcinoma.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Chitosan/chemistry , Drug Delivery Systems , Nanoparticles/chemistry , Stilbenes/chemistry , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/blood , Antineoplastic Agents, Phytogenic/pharmacokinetics , Avidin/chemistry , Biotin/chemistry , Cell Survival/drug effects , Female , Hep G2 Cells , Humans , Liver/metabolism , Liver Neoplasms/drug therapy , Male , Mice , Nanoparticles/administration & dosage , Resveratrol , Stilbenes/administration & dosage , Stilbenes/blood , Stilbenes/pharmacokineticsABSTRACT
A simple and sensitive high performance liquid chromatography method with UV detection was described for the determination of colchicine (COL) in mouse plasma. After single-step deproteinization by acetonitrile using berberine hydrochloride as an internal standard (I.S.), solutes were separated on a Diamonsil C(18) column (250 mm x 4.6 mm I.D., 5 microm particle size) (Dikma), using acetonitrile-0.15% phosphoric acid solution (27:73, v/v) as mobile phase (flow-rate 1.0 ml/min); wavelength of the UV detector was set at 350 nm. No interference from any endogenous substances was observed during the elution of COL and internal standard (I.S., berberine hydrochloride). The retention times for COL and I.S. were 11.23 min and 8.82 min, respectively. The limit of quantification was evaluated to be 1.5 ng/ ml and the limit of detection was 0.5 ng/ml. The method was used in the study of pharmacokinetics of COL after intravenous injection (i.v.) and intraperitoneal injection (i.p.). The result indicated that COL disappears from the plasma according to a three compartment open model.
Subject(s)
Chromatography, High Pressure Liquid/methods , Colchicine/blood , Spectrophotometry, Ultraviolet/methods , Animals , Berberine , Colchicine/administration & dosage , Colchicine/pharmacokinetics , Injections, Intraperitoneal , Injections, Intravenous , Mice , Models, Biological , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To optimize formulation of tanshinone II(A)-loaded PLGA nanoparticles and compare the difference of two methods in preparation and quality of nanoparticles. METHOD: The two methods were nanoprecipitation method and emulsion-evaporation method. Single factor experiments and central composite design and response surface method were used to optimize the formulation of nanoparticles. The nanoparticles were characterized at size, morphology, entrapment efficiency, drug loading, drug recovery rate, crystallinity and drug release in vitro. RESULT: The mean diameters were 225 nm and 183 nm, the entrapment efficiency were 95.49% and 87.99%, the drug loading were 2.03% and 0.16%, and the drug recovery rates were 38.42% and 17.59% respectively for nanoprecipitation method and emulsion-evaporation method. CONCLUSION: Nanoprecipitation method was better than emulsion-evaporation method for preparation of tanshinone II(A)-loaded PLGA nanoparticles.
Subject(s)
Lactic Acid/chemistry , Nanoparticles/chemistry , Phenanthrenes/isolation & purification , Polyglycolic Acid/chemistry , Polymers/chemistry , Salvia miltiorrhiza/chemistry , Technology, Pharmaceutical/methods , Abietanes , Chemical Precipitation , Crystallization , Emulsions , Particle Size , Phenanthrenes/chemistry , Plant Roots/chemistry , Plants, Medicinal/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Quality Control , VolatilizationABSTRACT
The development of molecular pharmacology and neuropharmacology accelerated the studies on molecular mechanism of Hypericum perforatum for depression. The clinical trials indicated that this galenical was superior to the traditional synthetic drugs for antidepression. This preparation had good tolerability and safety. Clinical pharmacokinetics and pharmacodynamics provided further evidence for clinical application of Hypericum. The clinical efficacy of Hypericum for depression was notable and credible.
