Electrochemotherapy (ECT) is a novel cancer treatment in which electric pulses (EPs) inducing cell membrane pored (electroporation) are used as a means of delivering antitumor drugs to the cytoplasm of cancer cells. The minimal thresholds of electric field strength of in vitro tumor cell line and tumor tissue are 450-650 V/cm and 400-600 V/cm, respectively. The typical electrical requirement is 600-1300 V/cm, pulse width of 100 micros, 8 pulses, 1 Hz. More than 10 kinds of antitumor drugs have been applied to ECT, in which the most efficacious drug is Bleomycin, and then Cisplatin. Some exciting inhibitory effects on cells in vitro and on solid tumors in clinical trials have been noticed. The factors influencing ECT effects include the electric parameters, diameter of electrode, distribution of electric field lines, size of tumor, model of drugs injection and kinds of drugs. Some questions of ECT are still open, such as the dosages and kinds of drugs for clinical trials, model of drug injection, influence on normal tissues, therapeutic mechanism.
Antibiotics, Antineoplastic ; administration & dosage ; Antineoplastic Agents ; administration & dosage ; Bleomycin ; administration & dosage ; Cisplatin ; administration & dosage ; Electric Stimulation Therapy ; methods ; Electrochemistry ; Electroporation ; methods ; Humans ; Neoplasms ; therapy

Pectin, a polysaccharide extracted from the cell wall of plants, was used as the drug carrier to synthesize the pectin-adriamycin conjugates (P(A)n). The structure of the conjugates was confirmed by UV and IR. The degree of esterification (DE) of the pectin was assessed, and it was found that DE significantly influenced the carboxy group contents, inherent viscosity and galacturonic acid contents of the pectin. The results of drug release test in vitro showed that the conjugate was stable in normal saline, but was gradually enzymolyzed to release the adriamycin in blood plasma and in lymph nodes. The results of lymphatic targeting study of P(A), demonstrated that the modification of DE or drug coupling capacity of pectin significantly influenced the lymphatic targeting characteristics of P (A)n. The adriamycin concentration of lymph nodes was 208 times higher than that of plasma after local injection of the P(A)n, of which the adriamycin content was 27.9% and the pectin was deesterificated 120 minutes by the use of hypothermy alkaline deesterification method.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Doxorubicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; chemistry ; Esterification ; Lymph Nodes ; metabolism ; Pectins ; administration & dosage ; pharmacokinetics ; Rabbits

The paper aimed to find the optimal combination and evaluation of the interactions of antitumor effect of the curcumin (Cur) and adriamycin (ADM) in vitro. According to the factorial design and data characteristics, the parameter method combined with the response surface approach were used to analyze the pharmacodynamic interactions of in vitro antitumor effects of the combination of Cur and ADM at different dosages. The results showed that the dose-effect relationship of the combination with the ratio of ADM-Cur 1:3 showed significant differences in comparison with either used alone. The dose-effect curve was shift left in combination. The combination of adriamycin (ADM, 0.693-2.132 micromol L(-1)) and curcumin (Cur, 2.047-6.304 micromol L(-1)) with a fixed ratio (1:3) showed a synergism. With increasing doses of the combination, there is an additive effect. Computer simulation showed a trend of decreasing difference between the observed and expected effects with the dose increasing in Cur from 6.304 to 16.0 micromol L(-1) and ADM from 2.132 to 5.3 micromol L(-1). The response surface analysis showed the optimal combination to be Cur 18.50 micromol L(-1) and ADM 3.89 micromol L(-1) with a ratio of 5:1. This study suggests that the parameter method combined with the response surface analysis provides richer and more reasonable information, and is helpful for quantitative design of drug combination therapy and to describe the nature and degree of drug interaction.
Algorithms ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Proliferation ; drug effects ; Computer Simulation ; Curcumin ; administration & dosage ; isolation & purification ; pharmacology ; Dose-Response Relationship, Drug ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Synergism ; Humans ; K562 Cells

As a novel targeting drug delivery system, acid-sensitive micelles have many advantages, such as increasing solubility of lipophilic drugs, acid-sensitive release, high drug loading, etc. They can load drugs though non-covalent encapsulation and covalent conjugation methods. In tumor tissues, drugs are released quickly from the depolymerized micelles with lipophilic copolymer protonation or lypohydrophilic copolymer hydrolysis and covalent conjugated drugs are released when the acid-sensitive covalent linkage breaks. This review mainly advances acid-sensitive micelles for the tumor targeting drug delivery systems from drug-loaded methods and release mechanisms.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Humans ; Hydrogen-Ion Concentration ; Lactates ; chemistry ; Micelles ; Paclitaxel ; administration & dosage ; pharmacology ; Polyethylene Glycols ; chemistry ; Polymers

AIMTo study the pharmaceutical characterization and pharmacokinetics of long-circulating liposomes containing daunorubicin.

METHODSThe morphology of daunorubicin long-circulating liposome was surveyed under the transmission electron microscope. The size of daunorubicin long-circulating liposomes was determined by laser scatter method. The entrapment efficiency and accelerative experiment stability of the daunorubicin long-circulating liposomes were examined. Visible spectrophotometry and the HPLC method were established for determination of the daunorubicin in the long-circulating liposomes. The percent release of daunorubicin from long-circulating liposomes in HBS (pH 7.5) and rat serum at 37 degrees C were examined. The pharmacokinetics in rats were studied.

RESULTSThe high entrapment efficiency (> 85%) and stabilized long-circulating liposomes could be achieved. The drug was slowly released from the daunorubicin long-circulating liposomes. The drug released from liposomes was less than 10% in 24 h. The T1/2 alpha and AUC of long-circulating liposome were higher than those in injections.

CONCLUSIONThe long-circulating liposomes prepared by us have high encapsulation efficiency and the pharmaceutical characterization showed good stability, they can be used for clinical purpose.

Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Daunorubicin ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Drug Carriers ; Liposomes ; Male ; Phosphatidylethanolamines ; Polyethylene Glycols ; chemistry ; Random Allocation ; Rats ; Rats, Wistar

The aims of the study were to prepare polyelectrolyte nanocapsules effected by acid phosphatease (ACP) and to study prolonged-releasing performance of the nanocapsules in vitro. Using the layer by layer (LbL) self-assembly technique, polyelectrolyte-beta-glycerophosphoric acid nanocapsules were prepared. The morphologies of the nanocapsules were characterized by transmission electron microscopy (TEM) and biocompatibility was well examined by cell-culture method. The drug adriamycin would be loaded in nanocapsules for concentration gradient, the encapsulation efficiency could be calculated. Nanocapsules were reacted with acid phosphatease standard and HepG2 cells that express the ACP, respectively. The prolonged-releasing of adriamycin was verified and tumor cells apoptosis were measured. TEM images showed that the nanocapsule sizes were between 200-300 nm. The material biocompatibility was good until the concentration of nanacapsule was up to 250 microg/mL. The drug encapsulation efficiency reached 68.12%. The release rate of polyelectrolyte (PAH/PSS-beta-glycerophosphoric acid)s nanocapsules was higher than in the control nanocapsules at 48 h (38% Vs 15%) after its reaction to the ACP standard (P < 0.05). Compared with the control, nanocapsules could significantly inhibit the growth of HepG2 cells that expressed the ACP, and the efficiency of cell apoptosis was 7.59% higher at 24 h (13.73 Vs 6.14, P < 0.05). Polyelectrolytes (PAH/PSS-beta-glycerophosphoric acid) nanocapsules in vitro have response to acid phosphatease by which prolonged-releasing can be affected. This property can be used for treatment of some malignant and benign diseases with elevated acid phosphatease level.
Acid Phosphatase ; pharmacology ; Antibiotics, Antineoplastic ; administration & dosage ; Delayed-Action Preparations ; chemical synthesis ; Doxorubicin ; administration & dosage ; Electrolytes ; chemistry ; Hep G2 Cells ; Humans ; Nanocapsules

Antibiotics, Antineoplastic ; administration & dosage ; Carcinoma, Hepatocellular ; therapy ; Chemoembolization, Therapeutic ; methods ; Doxorubicin ; administration & dosage ; Drug Carriers ; Follow-Up Studies ; Humans ; Liver Neoplasms ; therapy ; Male ; Microspheres ; Treatment Outcome

In this paper, we address the preparation of the EPC and HEPC sterically stabilized doxorubicin liposomes and report the data collected from further studies on pharmacokinetics in blood for choosing a better carrier in delivering the drugs. The pharmacokinetics of EPC and HEPC sterically stabilized liposomes (EPC-SSL, and HEPC-SSL) in Wistar rats were investigated by HPLC. The results showed that the mean residence time of HEPC-SSL in blood is 23.3 h, while that of EPC-SSL is 12.0 h. In conclusion, HEPC-SSL is a better carrier in delivering the drugs to the extravascular sites when compared with EPC-SSL.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; chemical synthesis ; pharmacokinetics ; Doxorubicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; chemistry ; Hydrogenation ; Liposomes ; Phosphatidylcholines ; chemistry ; pharmacology ; Rats

Restenosis following vascular revascularization remains an important clinical problem. Local drug delivery which can provide enough drug concentration in the lesion location without causing adverse systemic effect is an excellent solution for this question. We conducted a systematic literatory search on PubMed and CKNI through May 2014. After reviewing all related papers, we provided a comprehensive overview of the available drugs and techniques for local drug delivery that have been developed to prevent restenosis after peripheral vascular interventions, including innovations that have been tested only in animals as well as those already approved for clinical use. In brief, anti-proliferative drugs such as paclitaxel and sirolimus are the most used and suitable drugs for local delivery system. Additionally, some promising drugs including anti-inflammatory drugs, antioxidant drugs and drugs inhibiting cell proliferation and migration are already being tested in pre-clinical trials or animal models. At the same time, intraluminal and extraluminal delivery devices have also got a rapid development during the past decades. The efficacy of drug-eluting stent, drug-eluting balloon, porous and microporous balloon and the most recent drug-eluting bioresobable scaffold for preventing of restenosis in peripheral vessels have been demonstrated in humans or in animals, some of them even have received the CE mark in Europe. Endovascular microinfusion catheter and drug-loaded perivascular wraps have only been tested in animal models, more researches are needed. With the development of pharmacology and bioengineering, great strides will be made in the prevention of restenosis in the near future.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; Antibiotics, Antineoplastic ; administration & dosage ; Arteries ; Coronary Restenosis ; prevention & control ; Drug Delivery Systems ; Drug-Eluting Stents ; Humans ; Myocardial Revascularization ; Paclitaxel ; Sirolimus

PURPOSE: To evaluate the visual outcomes of retinoblastoma in the posterior pole (RBPP) treated with chemotherapy plus local treatments and to address the prognostic factors that influence such outcomes. METHODS: The medical records of patients with RBPP diagnosed at the Department of Pediatric Ophthalmology, Seoul National University Children's Hospital between August 1987 and September 2007 were reviewed retrospectively. Only those patients treated via primary chemotherapy plus local treatments were included. The presence of foveal involvement and tumors in the posterior pole before and after treatment, the type of regression pattern and the best corrected visual acuity (BCVA) of each patient were evaluated. RESULTS: A total of 13 eyes in 12 patients were included. The mean final BCVA for treated RBPP was 20/210 (range, hand motion to 20/16). However, eight eyes (61.5%) had an acuity of 20/200 or better and seven eyes (53.8%) had an acuity of 20/50 or better. The mean final BCVA was significantly better in cases with negative foveal involvement; however, four eyes (37.5%) with positive foveal involvement had an acuity of 20/200 or better. Tumors area in the posterior pole and the type of regression pattern were not significantly related to final BCVA. CONCLUSIONS: Over one half of the studied RBPP patients had working vision. Although the eyes had RBPP with positive foveal involvement, about one-third of the patients had working vision. Vision preservation should be considered when deciding on RBPP treatment.
Antibiotics, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration & dosage ; Cyclophosphamide/administration & dosage ; Doxorubicin/administration & dosage ; Etoposide/administration & dosage ; Eyeglasses ; Female ; Follow-Up Studies ; Fovea Centralis/pathology ; Humans ; Infant ; Male ; Prognosis ; Retinal Neoplasms/*drug therapy/pathology/*physiopathology ; Retinoblastoma/*drug therapy/pathology/*physiopathology ; Retrospective Studies ; Treatment Outcome ; Visual Acuity