Multi-compartment linear circulation mathematical model for targeted drug delivery systems was established on the bases of compartment theory and mass conservation theory. The function formulas of drug concentration-time in blood and target organ were established. According to this model, the drug concentration-time curve for the target organ can be plotted with reference to the data on blood. Based on the target organ drug concentration-time curve,the pharmacokinetics parameters of the target organ can also be calculated by the statistical moment. We further detected the practicability of the models by using the experimental data of drug concentration-time curve in blood and target organ of microspheres. The drug concentration-time curve in blood and in target organ predicted by mathematical model was agreed with that observed.
Albumins ; administration & dosage ; Drug Delivery Systems ; Humans ; Microspheres ; Models, Theoretical ; Pharmacokinetics

This review presents the most outstanding contribution in the field of polymeric nanoparticles used as targeting drugs delivery systems. Nanoparticles barrier is a novel kind of controlled release system for drugs which can effectively deliver the drug to a target site and increase the bioavailability and therapeutic benefit, while minizing the side effects. In this paper the applications of nanoparticles in the active, passive and physical targeting drugs carriers are reviewed.
Albumins ; administration & dosage ; Antibodies, Monoclonal ; administration & dosage ; Biological Availability ; Cyanoacrylates ; administration & dosage ; Drug Carriers ; Drug Delivery Systems ; Humans ; Nanotechnology ; Particle Size ; Polymers ; administration & dosage

INTRODUCTIONLymphoedema results from impaired lymphatic transport leading to the pathologic accumulation of protein-rich lymphatic fluid in the interstitial space, most commonly in the extremities. Primary lymphoedema, a developmental abnormality of the lymphatic system, may become evident later in life when a triggering event exceeds the capacity of normal lymphatic flow.

CLINICAL PICTUREWe present a 3-year-old nephrotic syndrome patient with an unusual localisation for primary lymphoedema.

TREATMENT AND OUTCOMEThe patient was treated with conservative approach and she was cured.

CONCLUSIONIn this particular case, lymphoedema developed at an unusual localisation, which has not been recorded before.

Albumins ; administration & dosage ; Child, Preschool ; Diuretics ; administration & dosage ; Female ; Furosemide ; administration & dosage ; Humans ; Infusions, Intravenous ; Lymphedema ; drug therapy ; etiology ; Nephrotic Syndrome ; complications ; Oliguria ; etiology

OBJECTIVETo evaluate the effect of a phospholipid-coated microbubble contrast agent for myocardium opacification in comparison with a albumin-coated microbubble contrast agent (Quanfuxian).

METHODSIn 10 dogs with single coronary artery stenosis involving the anterior descending branch or circumflex branch randomly received infusion of the two contrast agents through the femoral vein. The myocardial blood flow, heart rate and blood pressure were analyzed qualitatively and quantitatively. The concentration and the particle diameter of the two contrast agents were determined.

RESULTSThe concentration of the phospholipid-coated microbubbles was (1.06-/+0.22) x10(9)/ml, with a diameter of 3.04-/+0.34 microm, similar to the concentration and diameter of Quanfuxian ((1.31-/+0.33)x10(9)/ml and 2.88-/+0.58 microm, respectively, P>0.05). Both of the agents achieved grade three myocardium opacification, and produced no obvious effect on the heart rate and blood pressure. Quantitative analysis of myocardial opacification in terms of myocardial blood volume (A), blood velocity (beta), and blood flow (A x beta) revealed no significant difference between the two agents (P>0.05), and the parameters derived from the two agents showed good correlations (P<0.05, rA=0.809, r beta=0.932, rA.beta=0.925).

CONCLUSIONThe phospholipid-coated microbubble contrast agent shows good effect for myocardial opacification without significant difference from Quanfuxian. Both of the agents are good ultrasound contrast agents for quantitative analysis of myocardium blood flow.

Albumins ; chemistry ; Animals ; Contrast Media ; administration & dosage ; chemistry ; Coronary Stenosis ; diagnostic imaging ; Dogs ; Echocardiography ; methods ; Female ; Male ; Microbubbles ; Phospholipids ; chemistry

AIMTo develop a method for direct determination of perfluoropropane in canine whole blood and to study its pharmacokinetics after a suspension of perfluoropropane-containing albumin microcapsules was administered intravenously.

METHODSPerfluoropropane-containing albumin microcapsule suspension was administered intravenously to anesthetized canines at the dosage of 0.6 mL x kg(-1). Whole blood samples were collected and added directly into the purging glass tube in Tekmar 3000 Purge and Trap Concentrator coupled with a GC-MS for the determination of perfluoropropane. The pharmacokinetic parameters of perfluoropropane were calculated by non-compartment model statistics.

RESULTSThe linear range was 0.0168-4.03 mg x L(-1). The main pharmacokinetic parameters of perfluoropropane was obtained as follows: mean residence time (MRT) was (63 +/- 5) s, T1/2 was (44 +/- 4) s, Tmax was 30 s, Cmax was (2.20 +/- 0.20) mg x L(-1), AUC0-infinity was (96 +/- 11) mg x s x L(-1).

CONCLUSIONThe method is sensitive, specific and simple. It can be used to determine fluorocarbon contained in microcapsule ultrasound contrast agents for studying its pharmacokinetics.

Albumins ; Animals ; Area Under Curve ; Capsules ; Dogs ; Fluorocarbons ; administration & dosage ; blood ; pharmacokinetics ; Gas Chromatography-Mass Spectrometry ; methods ; Injections, Intravenous

OBJECTIVETo develop a method for quantitative collection of exhaled gas in anesthetized dogs at given time following intravenous administration of octafluoropropane (OFP)-containing human albumin micropheres for assessing the gas kinetics of OFP.

METHODSOFP-containing albumin micropheres were administered intravenously at 0.4, 0.8 and 1.2 ml/kg, respectively, in anesthetized and ventilated dogs. The exhaled air samples were analyzed by gas chromatography-tandem mass spectrometry (GC-MS-MS).

RESULTSThe correlation curve between the area under curve (AUC) and administered dose was roughly linear (Y=1162.5X-417.38, r square=0.949 9). The total recovery rate was (119.49-/+27.62)% which was not significantly different from the rate of 100% (P>0.05). GC-MS-MS was accurate, sensitive, precise and applicable for OFP determination.

CONCLUSIONThe sampling method is useful for characterizing OFP pharmacokinetics in dogs, and also applicable for studying the pharmacokinetics of other gas-containing drugs.

Albumins ; administration & dosage ; analysis ; pharmacokinetics ; Animals ; Dogs ; Exhalation ; Female ; Fluorocarbons ; administration & dosage ; analysis ; pharmacokinetics ; Gas Chromatography-Mass Spectrometry ; methods ; Humans ; Injections, Intravenous ; Male ; Microspheres ; Reproducibility of Results

OBJECTIVETo prepare carbon nanoparticle-paclitaxel suspension(CNPS) and to study the pharmacokinetics of intraperitoneal chemotherapy with CNPS.

METHODSSaturated absorption capacity of carbon nanoparticle suspension (CNS) and paclitaxel were detected by high performance liquid chromatography in order to prepare the above suspension. Wistar rats were randomly divided into the experimental group (A) and the control group (B), to which intraperitoneal injections of CNPS and paclitaxel were given respectively. At different time points, measure the blood samples, mesenteric lymph nodes, and intraperitoneal lavage fluid were collected to measure the concentration of paclitaxel.

RESULTSOne ml CNS could absorb 7 mg paclitaxel by maximum. The ratio of area under the curve (AUC) in the plasma of group A to group B was 0.63. The ratio of AUC in lymph nodes of group A to group B was 0.75 and that in intraperitoneal lavage fluid was 1.25. The metabolic half-life (t1/2) of paclitaxel in the plasma of group A was 1.61 times as long as that of group B. The t1/2 of paclitaxel in intraperitoneal lavage fluid of group A was 0.88 as long as that of Group B. The t1/2 of paclitaxel in lymph nodes of group A was 1.10 as long as that of Group B.

CONCLUSIONSCNS has a high absorption capacity with paclitaxel. Intraperitoneal chemotherapy by CNPS is characterized by low drug concentration in the blood, high drug concentration in the peritoneal cavity and high safety. However, the targeting and lymphatic retention effect are not significant. The mechanism warrants further investigation.

Albumin-Bound Paclitaxel ; Albumins ; chemistry ; pharmacokinetics ; Animals ; Area Under Curve ; Carbon ; chemistry ; Injections, Intraperitoneal ; Lymph Nodes ; Nanoparticles ; administration & dosage ; Paclitaxel ; chemistry ; pharmacokinetics ; Rats ; Rats, Wistar

OBJECTIVETo observe the effect of parenteral nutrition (PN) with branched-chain amino acid supplementation on protein metabolism after partial hepatectomy in rats with liver cirrhosis.

METHODSEighteen rats with liver cirrhosis were randomly divided into pre-operation group (n=6), post-operation 8.5% Novamin PN group (n=6) and post-operation 10% Hepa PN group (n=6), with 6 normal rats severing as the normal control group. Five days after the operation, serum albumin (ALB), insulin-like growth factor I (IGF-1) and plasma amino acid spectrum were measured, and ALB mRNA level in the liver was assayed using RT-PCR.

RESULTSPostoperative serum ALB was similar between 10% Hepa PN and 8.5% Novamine PN groups, but the rats in the latter group showed significantly increased serum IGF-1 level, Fischer ratio and hepatic ALB mRNA expression (P<0.05).

CONCLUSIONAdministration of PN with branched-chain amino acid supplementation can ameliorate plasma amino acid spectrum and increase protein synthesis in rats with liver cirrhosis after partial hepatectomy.

Albumins ; metabolism ; Amino Acids, Branched-Chain ; administration & dosage ; therapeutic use ; Animals ; Hepatectomy ; Insulin-Like Growth Factor I ; metabolism ; Liver Cirrhosis ; therapy ; Parenteral Nutrition ; Rats ; Rats, Sprague-Dawley

Albumin has been widely used in patients with cirrhosis in an attempt to improve circulatory and renal functions. The benefits of albumin infusions in preventing the deterioration in renal function associated with large-volume paracentesis, spontaneous bacterial peritonitis, and established hepatorenal syndrome in conjunction with a vasoconstrictor are well established. While some of these indications are supported by the results of randomized studies, others are based only on clinical experience and have not been proved in prospective studies. The paucity of well-designed trials, the high cost of albumin, the lack of a clear-cut survival benefit, and fear of transmitting unknown infections make the use of albumin controversial. The recent development of the molecular adsorbent recirculating system, an albumin dialysis, is an example of the capacity of albumin to act by mechanisms other than its oncotic effect. Efforts should be made to define the indications for albumin use, the dose required, and predictors of response, so that patients gain the maximum benefit from its administration.
Albumins/*administration & dosage/adverse effects ; Ascites/therapy ; End Stage Liver Disease/physiopathology/*therapy ; Evidence-Based Medicine ; Hepatorenal Syndrome/therapy ; Humans ; Liver Cirrhosis/therapy ; Plasma Substitutes/*administration & dosage/adverse effects ; Sorption Detoxification/adverse effects/*methods ; Treatment Outcome

OBJECTIVEThe purpose of this study was to investigate the cisplatin release in peripheral blood and tumor tissue after cisplatin-loaded albumin microspheres (CDDP-AMS) were infused through lingual artery for treating carcinoma of tongue.

METHODSAnticancer agent cisplatin was encapsulated with biodegradable and non-antigenic albumin. The cisplatin-loaded albumin microspheres, which were 56.3 microns in diameter, were used for treating 7 patients with squamous carcinoma of tongue by infusing through lingual artery. The cisplatin in peripheral venous blood and carcinoma tissue were measured for analyzing the drug release in vivo.

RESULTSConcentration of the drug in peripheral venous blood increased to the highest level in 90 minutes after CDDP-AMS was infused through lingual arterial and still could be detected until 10th day. The cisplatin concentration in tumor tissue kept considerably stable and could be detected until 17 days.

CONCLUSIONCDDP-AMS had the effect of controlled release in vive. Effective and steady local drug concentration played the role of killing tumor cells, the low concentration in peripheral blood reduced the side effects of cisplatin to minimum as well. It is concluded that CDDP-AMS is a useful and recommendable method for treating the carcinoma of tongue.

Adult ; Aged ; Albumins ; Antineoplastic Agents ; administration & dosage ; blood ; Arteries ; Carcinoma, Squamous Cell ; drug therapy ; Cisplatin ; administration & dosage ; blood ; Delayed-Action Preparations ; Drug Carriers ; Female ; Humans ; Infusions, Intra-Arterial ; Male ; Microspheres ; Middle Aged ; Tongue ; blood supply ; Tongue Neoplasms ; drug therapy