ABSTRACT
A novel liposome with temperature-sensitivity for vinorelbine bitartrate (VB) was designed to enhance VB targeted delivery and antitumor effect. Liposomes without drugs were prepared by thin film hydration, and then VB was entrapped into liposomes by pH gradient loading method. The mean particle size of the liposomes was about 100 nm, and the drug entrapment efficiency was more than 90%. Stability data indicated that the liposome was physically and chemically stable for at least 6 months at 4 °C. In vitro drug release study showed that drugs hardly released at 37 °C; while at 42 °C, drugs released quickly. For in vivo experiments, the lung tumor model was established by subcutaneous inoculation of cell suspension on mice, liposomes and free VB were injected i.v. in mice, followed by exposure the tumors to hyperthermia (HT) for 30 min after administration. The ratio of inhibition tumor of temperature-sensitive liposomes group was significantly higher than the normal injection group. Combining temperature-sensitive liposomes with HT enhanced the delivery of VB and, consequently, its antitumor effects. This liposome could potentially produce viable clinical strategies for improved targeting and delivery of VB for treatment of cancer.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Drug Delivery Systems/methods , Liposomes/chemistry , Vinblastine/analogs & derivatives , Animals , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Control Groups , Disease Models, Animal , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Doxorubicin/pharmacology , Drug Carriers/chemistry , Drug Compounding , Drug Stability , Hot Temperature , Injections , Liposomes/administration & dosage , Liposomes/pharmacology , Lung Neoplasms/drug therapy , Mice , Random Allocation , Suspensions , Vinblastine/administration & dosage , Vinblastine/chemistry , Vinblastine/pharmacology , VinorelbineABSTRACT
We intend to form photosensitive block copolymer micelles for controllable release of encapsulated substances. Here, we designed and synthesized a new photocleavable cross-linker (2-nitrophenyl ethylene glycol dimethacrylate) for methyl methacrylate (MMA) atom transfer radical polymerization. Four different ratios (0:1, 1:26, 1:16, 1:8.8) of the photocleavable cross-linker to MMA monomer were used and four block copolymers (P0, P1, P2, P3) were synthesized with PEO-Br as the macroinitiator. Gel permeation chromatography and (1) H NMR studies showed that linear polymer molecules could be cross-linked by the photocleavable linker. The fluorescence studies of the encapsulated Nile Red (NR) showed that there were lower critical micelle concentrations for the polymer P1, P2 and P3 than polymer P0. And dynamic light scattering and SEM confirmed the formation of polymer micelles. Photolysis experiments demonstrated that NR encapsulated in the polymer micelles could be released upon UV irradiation (365 nm, 11 mW cm(-2)) due to the breakage of the photocleavable linker and the generation of more hydrophilic acid moieties, which destabilized polymer micelles. Our study shows a new strategy for the possibility of photocontrollable drug release for hydrophobic drugs.
Subject(s)
Delayed-Action Preparations/metabolism , Drug Carriers/metabolism , Methacrylates/metabolism , Oxazines/metabolism , Photolysis/radiation effects , Polymers/metabolism , Chromatography, Gel , Delayed-Action Preparations/chemical synthesis , Drug Carriers/chemical synthesis , Fluorescence , Hydrogen-Ion Concentration , Methacrylates/chemical synthesis , Micelles , Microscopy, Electron, Scanning , Nitrophenols/chemistry , Nuclear Magnetic Resonance, Biomolecular , Polyethylene Glycols/chemistry , Polymerization , Polymers/chemical synthesis , Ultraviolet RaysABSTRACT
OBJECTIVE: To study the effect of quercetin on acyclovir intestinal absorption. METHODS: The everted gut sac and in vitro intestinal absorption tests were performed. The acyclovir transport quantity was determined by HPLC method. RESULTS: The everted gut sac study showed that quercetin significantly inhibited the function of intestinal P-glycoprotein P-gp . The acyclovir transport quantities from mucosa to serosa space, which incubated with 5, 10, 80 mg/L quercetin solution or 10 mg/L verapamil solution, were increased 0.3, 0.6, 1.0 and 1.0-fold higher than acyclovir alone, respectively. The transport quantity caused by inhibition of intestinal P-gp function fitted with Boltzmann equation. The in vitro intestinal absorption test indicated that the transported acyclovir from serosa to mucosa, incubated with 2, 5, 10 mg/L quercetin solution, was significantly decreased compared with acyclovir alone. CONCLUSION: Quercetin can enhance acyclovir intestinal absorption by inhibiting the function of P-gp.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Acyclovir/pharmacokinetics , Intestinal Absorption/drug effects , Quercetin/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/physiology , Animals , Biological Transport , Chromatography, High Pressure Liquid , Male , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To study the hypoglycemic effects of bis(maltolato) oxovanadium (IV) (BMOV) after administration on diabetic rats by different routines, and its possible mechanisms. METHODS: Diabetic rats were created by intraperitoneal administration of Alloxan. BMOV was administered by single intraperitoneal injection, oral gavage, subcutaneous injection, bolus intravenous injection, or slow bolus intravenous injection(7-8 min). Plasma glucose levels were determined with blood glucose assay kits using the glucose oxidase method, while the plasma insulin concentrations were monitored by the insulin assay kits using Radioimmunoasssay (RIA) method. RESULTS: Plasma glucose levels were significantly decreased after administration of BMOV by all routes except intravenous injection. Food and fluid intake by the diabetic rats were also reduced. There was no significant increase in plasma insulin concentration. CONCLUSION: BMOV administered by oral gavage, subcutaneous injection and intraperitoneal injection has obvious effect of decreasing plasma glucose levels on diabetic rats, and the hypoglycemic effect of BMOV was not achieved by increasing the plasma insulin concentration.
