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PubMed2001

A prospective study of the workload of a newly formed PEG advice team.

BACKGROUND: A multidisciplinary advice team may be the optimal way of providing the long-term nutritional and percutaneous endoscopic gastrostomy (PEG)-related care for patients dependent on PEG feeding but the workload involved is unknown. AIM: To study prospectively the workload of a proactive, multidisciplinary PEG advice team over a 2-year period. METHODS: Separate documentation from main case notes of each episode of the team's contact with PEG or potential PEG patients, including assessment, advice and therapy given, from the time of its establishment, for four consecutive 6-monthly periods. RESULTS: During the audit, 89 patients were referred to the team for consideration of PEG insertion and PEGs were placed in 74. Eighty-nine additional patients were referred for follow up having had a PEG placed elsewhere. During the four audit periods the rate of new PEG insertions increased by 53%, the rate of PEG replacements by 315%, and the number of patients under the team increased from 16 to 70, an increase of 337%. Numbers of inpatient and outpatient consultations, and visits to other institutions by members of the team increased commensurately. CONCLUSIONS: The rapidly increasing workload of the team suggests it is playing a valued role but there are significant resource implications.

Enteral Nutrition↗
PubMed2001

Optimizing pretransfusion antibody detection and identification: a parallel, blinded comparison of tube PEG, solid-phase, and automated methods.

BACKGROUND: The ideal pretransfusion testing strategy identifies maximal significant antibodies at minimal cost. Objectives of this study were to compare the characteristics of three testing methods and determine their optimal incorporation into the following generic testing sequence: 1) screen, for antibodies 2) if results are positive, use primary identification method, 3) if results are inconclusive, use secondary identification method. STUDY DESIGN AND METHODS: A total of 2000 consecutive, unselected, coded specimens were tested with three screening methods-PEG IAT, manual and automated solid phase red cell adherence assay (SPRCA). Of 202 positive results, 187 were of sufficient volume and were tested with both PEG and manual SPRCA identification panels, yielding 82 with significant antibodies, plus one that was negative by both methods found on retrospective review of nonstudy results. Calculations were made on the 1985 volume-sufficient specimens, simulating the possible testing permutations. RESULTS: Manual SPRCA was the most sensitive antibody screen (67/83 = 81%) and the least specific (1840/1902 = 97%); automated SPRCA was the least sensitive (54/83 = 65%) and most specific (1883/1902 = 99%); and PEG was intermediate in both sensitivity (64/83 = 77%) and specificity (1860/1902 = 98%). Of the identification panels, manual SPRCA identified more antibodies than PEG (67 versus 66) but had more inconclusive results (41 versus 20). Of overall strategies, manual SPRCA screening with either sequence of identification methods identified the most antibodies (66). The combination of PEG screen, PEG identification, and manual SPRCA identification identified slightly fewer antibodies (63) but had the lowest reagent cost, total (reagent plus labor) cost, and cost per antibody identified. The sequence of automated SPRCA screening with manual SPRCA identification, and PEG identification had the lowest hands-on time. CONCLUSIONS: The most cost-effective pretransfusion strategy is PEG screen with PEG identification, plus manual SPRCA identification when PEG identification is inconclusive.

Antibodies↗
PubMed2006

Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: no additional benefit of combination with lamivudine.

BACKGROUND: The effect of pegylated interferon or its combination with lamivudine on liver histology of patients with chronic hepatitis B (CHB) is unknown. In a double-blinded, randomized, multi-center study we assessed histological changes in 110 hepatitis B e-antigen (HBeAg)-positive CHB patients treated for 52 weeks with Pegylated interferon alpha-2b (PEG-IFN) in combination with either lamivudine or placebo. Liver biopsies were taken before and at the end of treatment. All biopsies were blinded and scored according to the Ishak system. RESULTS: Necroinflammatory score improved (defined as a decrease of at least two points) in 25 patients (48%) of the PEG-IFN/lamivudine combination therapy group and in 31 patients (53%) of the PEG-IFN monotherapy group. The fibrosis score improved (decrease of at least 1 point) in 17 patients (33%) of the combination therapy group vs. 13 patients (22%) of the PEG-IFN monotherapy group (P=0.23). Responders (n=42), defined as serum HBeAg negative at the end of therapy, showed a larger decline in necroinflammatory score than non-responders (mean decline 2.3 and 1.2 points, respectively, P=0.02). Among patients receiving PEG-IFN monotherapy necroinflammation improved more frequently in responders (78% of responders vs. 43% of non-responders, P=0.01) and in patients who showed normalization of ALT (76% of patients with normal ALT vs. 40% of patients with abnormal ALT, P=0.01). Fibrosis score in the PEG-IFN monotherapy group improved more often in responders (39%) than in non-responders (15%, P=0.04). In the PEG-IFN/lamivudine combination therapy group, we found no significant association between virological and biochemical endpoints and histological improvement. CONCLUSIONS: Treatment with PEG-IFN therapy improves liver necroinflammation in HBeAg-positive CHB patients, particularly in responders to therapy. PEG-IFN also improves fibrosis in responders. Addition of lamivudine to PEG-IFN did not further improve the histological outcome.

Adult↗
PubMed2004

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial.

BACKGROUND: Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. AIMS: To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. PATIENTS: One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. METHODS: After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis < or =1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. RESULTS: A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. CONCLUSIONS: PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.

Adolescent↗
PubMed2026

HBsAg decline and clearance with peg-IFN therapy added to nucleos(t)ide analogues: an individual participant data meta-analysis of prospective trials (PROSPER).

BACKGROUND: Peg-interferon (peg-IFN) plays an increasingly important role in HBV cure strategies, either in combination with novel antivirals, as a lead-in or as consolidation treatment. OBJECTIVE: We aimed to provide estimates of hepatitis B surface antigen (HBsAg) decline and clearance that can be achieved with peg-IFN addition to nucleos(t)ide analogue (NA) therapy. DESIGN: This is a post hoc meta-analysis of individual participant data from eight clinical trials involving chronic hepatitis B patients on NA therapy who received peg-IFN add-on. The primary endpoint was HBsAg loss at end of follow-up (EOF, 6-12 months after end of peg-IFN). Secondary analyses focused on HBsAg decline. RESULTS: 581 patients were included. At the start of peg-IFN therapy (SOT), 44% were hepatitis B envelope antigen (HBeAg) positive, mean HBsAg level was 3.03 log10 IU/mL (HBsAg<100: 12%; 100-1000: 28%; &#x2265;1000: 60%), and planned duration of peg-IFN was 48 weeks in 496 patients (85%).At EOF, 50 (8.6%) patients achieved HBsAg loss (HBsAg<100/100-1000/&#x2265;1000: 37.7/9.8/2.3%, p<0.001) Findings were consistent across ethnicities (Caucasian: 30.0/8.7/3.6%; Asian: 39.3/9.2/2.2%). In patients with SOT HBsAg&#x2265;1000 IU/mL, levels <1000 and <100 were achieved in 29.7% and 8.9% at 24 weeks and in 47.5% and 16.3% at 48 weeks of peg-IFN therapy, respectively. CONCLUSION: Peg-IFN add-on results in HBsAg loss in 18% of patients with SOT HBsAg<1000 IU/mL, and in 38% if SOT HBsAg<100 IU/mL. Among patients with higher HBsAg levels, peg-IFN could be used to reduce HBsAg to below thresholds associated with response to novel compounds.

Humans↗
PubMed2003

Effects of PEG-hirudin in clotting parameters and platelet function and its interaction with aspirin in healthy volunteers.

The purpose of this study was to investigate the pharmacodynamics of PEG-Hirudin and its potential interactions with acetylsalicylic acid (ASA 325 mg once daily from days 1-3). In a randomized, 2-way cross-over trial, 6 healthy volunteers received PEG-Hirudin (i.v. bolus of 0.2 mg/kg + 0.02 mg/kg/h for 24 hours) and placebo (i.v. bolus + 24-hour infusion). In a further randomized, 3-way cross-over trial another 9 healthy volunteers received ASA (325 mg) or oral placebo from days 1 to 3 and PEG-Hirudin (0.2 mg/kg + 0.02 mg/kg/h for 24 h) or i.v. placebo on day 3. Assessments included bleeding time (BT), collagen (1 microgram ml(-1))-induced platelet aggregation (CIPA), platelet adhesion, ecarin clotting time (ECT), activated clotting time (ACT), plasma anti-factor IIa activity (aIIa), and activated partial thromboplastin time (aPTT). Ten minutes after the PEG-Hirudin injection/starting the infusion, mean plasma concentration was 3.1 microgram/mL and aPTT, ECT, and ACT were prolonged up to 80, 309, and 233 seconds, respectively. During the last 8 hours of the 24-hour infusion mean PEG-Hirudin plasma concentration was 1.3 microgram/mL. In the interaction study, ASA significantly inhibited CIPA. At 6 hours after administration, on day 3 mean BT was 6.5 minutes after PEG-Hirudin alone, 18.2 minutes after ASA alone, and 32.9 minutes after combined administration of ASA and PEG-Hirudin. PEG-Hirudin (0.2 mg/kg + 0.02 mg/kg/h for 24 hours) administered alone or together with 325 mg ASA proved to be safe in healthy volunteers. Combined use of PEG-Hirudin and ASA significantly increased the mean bleeding time compared to ASA or PEG-Hirudin monodrug administration. None of the clotting parameters or platelet function tests correlated with the prolongation of the bleeding time.

Aspirin↗
PubMed2000

Improved imaging of infections by avidin-induced clearance of 99mTc-biotin-PEG liposomes.

UNLABELLED: This article describes the preparation and optimization of biotin-polyethyleneglycol (PEG) liposomes and their application in experimental infection models to improve the scintigraphic imaging of infection and inflammation. METHODS: Biotin was coupled to PEG-distearoylphosphatidylethanolamine (DSPE) and subsequently incorporated in the PEG liposomes. Biotinylated liposomes were radiolabeled with 99mTc-hydrazinonicotinamide. In vitro binding studies were performed to find the optimal biotin concentration in the liposomes. In rats the biodistribution of the 99mTc-biotin-PEG liposomes was compared with the biodistribution of normal (nonbiotinylated) 99mTc-PEG liposomes. Furthermore, in vivo studies in rats were performed to study both the effect of the biotin content and the optimal avidin dose for efficient clearance of the liposomes. Liposomes containing 0.5 or 1.0 mol% biotin-PEG-DSPE were compared in rats with a Staphylococcus aureus infection in the left calf muscle. Avidin was injected 4 h after injection of the liposomes. RESULTS: Biotinylation of the liposomes did not affect their in vivo behavior. All biotin-PEG liposome formulations tested showed good in vitro avidin binding with 50% inhibitory concentrations ranging from 36 to 8 micromol/L. With avidin doses higher than 100 microg, both preparations rapidly cleared from the circulation. As a result, abscess-to-blood ratios increased 5-fold. To illustrate the potential of the avidin-induced clearance of radiolabeled PEG liposomes, we also studied the 99mTc-biotin-PEG liposomes in rabbits with a subcutaneous S. aureus abscess. The infection was visualized only after injection of 100 microg avidin. CONCLUSION: This study shows that biotin-coated 99mTc-PEG liposomes in combination with the injection of avidin can lead to improved imaging of infection or inflammation localized especially in regions with high blood-pool activity.

Abscess↗
PubMed2000

[Percutaneous endoscopic gastrostomy (PEG)--analysis in one hospital].

Percutaneous endoscopic gastrostomy (PEG) has been investigated over the past 5 years at the author's hospital, together with the establishment of home PEG on a trial basis. PEG was performed in 176 cases from 1995 to 1999 with the goal of nutritional management, and in 26 cases with the goal of decompression drainage of the digestive tract. Patients who could be transferred to home management due to the establishment of the PEG included 92 (52%) with the goal of nutrition and 4 (15%) for decompression drainage. There is no remarkable difference in the effective treatment period between home and hospital management, and patients who could be transferred to their own homes were thus able to spend most of their remaining time at home; therefore, PEG contributes to home care. Complications associated with the establishment of PEG occurred in 17 (8.4%) patients, the majority of which were absesses at the site of insertion. Three patients who underwent PEG at home experienced no complications and could be transferred to parenteral nutrition via PEG. PEG is a useful method for nutritional management and digestive tract drainage, and contributes to home treatment and the improvement of patient quality of life. We would like to attempt further use of these methods including home PEG.

Aged↗
PubMed2001

Aggregation of human RBC in binary dextran-PEG polymer mixtures.

The present study was prompted by prior reports suggesting that small polymers can affect RBC aggregation induced by large macromolecules. Human RBC were washed and re-suspended in isotonic buffer solutions containing 72.5 kDa dextran (DEX 70, 2 g/dl) or 35.0 kDa poly(ethylene glycol) (PEG 35, 0.35 g/dl), then tested for aggregation in these solutions with and without various concentrations of smaller dextrans (10.5 and 18.1 kDa) or PEGs (3.35, 7.5 and 10.0 kDa). RBC aggregation was measured at stasis and at low shear using a photometric cone-plate system (Myrenne Aggregometer) and RBC electrophoretic mobility (EPM) in the various polymer solutions via an automated system (E4, HaSoTec GmbH). Our results indicate: (1) a heterogeneous effect with greater reduction of aggregation for small PEGs added to DEX 70 or for small dextrans added to PEG 35 than for small polymers of the same species; (2) for cells in DEX 70, aggregation decreased with increasing molecular mass and concentration of the small dextrans or PEGs; (3) for cells in PEG 35, small dextrans decreased aggregation with increasing molecular mass and concentration, whereas small PEGs had minimal effects with a minor influence of concentration and an inverse association between molecular mass and inhibition of aggregation. RBC EPM results indicated the expected polymer depletion for cells in DEX 70 or PEG 35, and that small PEGs yielded greater EPM values than small dextrans for cells in PEG 35 whereas the opposite was true for cells in DEX 70. Interpretation of our results in terms of the depletion model for RBC aggregations appears appropriate, and our findings are consistent with the assumption that inhibition of aggregation occurs because of an increase of small molecules in the depletion region. Our results thus suggest the merit of further studies of red blood cell aggregation in binary polymer systems.

Adult↗
PubMed2001

PEG adsorption of autoantibodies causes loss of concomitant alloantibody.

Use of polyethylene glycol (PEG) to promote adsorption of autoantibodies is reported to give good recovery of concomitant alloantibodies. In initial experiments, PEG and ZZAP (Ficin and DTT) adsorption procedures were compared for removal of autoantibody and recovery of alloantibody. Postadsorption studies (n = 11) were performed and hemagglutination scores compared. In subsequent studies, equal volumes of alloantibody containing sera, PEG, and antigen-negative red blood cells (RBCs) were used in twofold adsorption experiments. Saline was substituted for PEG for control purposes. Postadsorption titers and immunoglobulin levels were determined. Autoantibodies were completely removed by both methods (n = 5); better by PEG (n = 3); better by ZZAP (n = 1); and not adsorbed (n = 1), and partially adsorbed by both (n = 1). Alloantibody recovery was comparable in three cases (E, K, Jka) but weaker by at least one reaction grade in four (K,E, Jka, and antibody to low-frequency antigen). The latter anti-Jka reacted 1+ with Jk(a+b+) RBCs after ZZAP adsorption but was nonreactive with the same RBCs following PEG adsorption. Titers of six alloantibodies adsorbed with antigen-negative RBCs in PEG were markedly weaker (range 2 to 8) compared to saline controls (range 4 to 32). IgG levels for PEG adsorbed (range 128 to 243 mg/dL) were 50% lower than controls (range 265 to 505 mg/dL). Although PEG adsorption is effective in removing autoantibody, the precipitation of immunoglobulin by PEG may result in failure to detect underlying alloantibody.

Journal Article↗
PubMed2000

Preparation of a PEG-grafted phospholipid Langmuir-Blodgett monolayer for blood-compatible material.

In order to develop a versatile model for blood-compatible materials, we studied morphology and platelet adhesion of a dipalmitoyl-phosphatidylcholine (DPPC)/dipalmitoyl-phosphatidylethanolamine-polyethylene glycol (PEG lipid) mixed monolayer. This monolayer, which mimics the cell membrane structure, consists of two heterogeneous layers, that is, a PEG layer lying on top of a phospholipid monolayer. The DPPC/PEG lipid mixed monolayer was prepared using the Langmuir-Blodgett (LB) Technique. The monolayer was transferred onto a silanized glass substrate by the down-stroke mode, at a surface pressure of 25 mN/m. The transfer efficiency achieved unity at all times. The morphologies of PEG chains on the phospholipid monolayer in water, in a dried state, and in a hydrated state were evaluated using Pi-A isotherm, ellipsometry, and atomic force microscopy (AFM), respectively. When the concentration of PEG lipid was below 1 mol %, the PEG chains could cover the DPPC surface completely in water, but not in the dried state. On the other hand, the PEG chains could cover the phospholipid surface completely in a dried state, as well as in water, when the PEG lipid concentration was above 3 mol %. These PEG chains, showing a brush-type conformation in water, were highly packed and had a bulky structure at the surface in the dried state as well as in the hydrated state. A bulky and extended PEG layer, above 3 mol % concentration, was greatly effective in the prevention of platelet adhesion.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Reduction of fibrinogen adsorption on PEG-coated polystyrene surfaces.

Reduction of protein adsorption by coating surfaces with polyethylene glycol (PEG) is well documented. The present work has four goals related to these previous studies: first, to develop chemistry providing densely packed, covalently bound PEG on polystyrene (PS); second, to determine the ability of these modified surfaces to reject fibrinogen; third, to compare the protein-rejecting ability of branched and linear PEGs; and fourth, to examine the utility of an ELISA-type procedure for measuring protein adsorption. It was found that PEG-epoxide could be readily coupled to amine groups of poly(ethylene imine) (PEI), which had been preadsorbed onto an oxidized PS surface. The PEG groups on branched PEGs appear to act as an excluded volume to repel proteins, similar to arguments previously raised for linear PEGs. The results of protein adsorption studies showed that fibrinogen adsorption is significantly reduced by coating polystyrene with either linear or branched PEGs of 1500 to 20,000 in molecular weight. The ELISA technique was found to be equivalent in sensitivity to radiolabeled fibrinogen for estimating adsorption levels. It is expected that PEG-coated PS will have much utility in a variety of biomedical applications.

Adsorption↗
PubMed2005

Modification of polyurethaneurea with PEG and YIGSR peptide to enhance endothelialization without platelet adhesion.

Improved endothelialization without platelet adhesion is essential to enhance the long-term patency of synthetic vascular grafts and other blood-contacting devices. We have developed a dually modified polyurethaneurea by incorporating endothelial cell adhesive YIGSR peptide sequences as chain extenders and nonthrombogenic PEG as a soft segment (PUUYIGSR-PEG) in the polymer backbone. PUUYIGSR-PEG was successfully synthesized and characterized by proton NMR, FTIR, GPC, DSC, ESCA, and contact angle measurement. Despite having similar molecular weight, the peptide/PEG-modified polyurethaneurea (PUUYIGSR-PEG) showed superior mechanical properties compared to the control PEG-modified polyurethaneurea (PUUPPD-PEG). Virtually no platelet adhesion was observed on PUUYIGSR-PEG, while endothelial cell adhesion, spreading, and migration were significantly greater on PUUYIGSR-PEG compared to PUUPPD-PEG. Thus, this bioactive polymer may be an appropriate biomaterial for small diameter vascular grafts.

Amino Acid Sequence↗
PubMed2005

Tissue anti-adhesion potential of ibuprofen-loaded PLLA-PEG diblock copolymer films.

This study was designed to evaluate the effect of polyethylene glycol (PEG) and nonsteroidal anti-inflammatory drug (ibuprofen) on the prevention of postsurgical tissue adhesion. For this, poly(L-lactic acid) (PLLA)-PEG diblock copolymers were synthesized by ring opening polymerization of L-lactide and methoxy polyethylene glycol (Mw 5000) of different compositions. The synthesized copolymers were characterized by gel permeation chromatography and 1H-nuclear magnetic resonance spectroscopy. PLLA-PEG copolymer films were prepared by solvent casting. The prepared copolymer films were more flexible and hydrophilic than the control PLLA film, as investigated by the measurements of glass transition temperature, water absorption content, and water contact angle. The drug release behavior from the ibuprofen (10 wt%)-loaded copolymer films was examined by high performance liquid chromatography. It was observed that the drug was released gradually up to about 40% of total loading amount after 20 days, depending on PEG composition; more drug release from the films with higher PEG compositions. In vitro cell adhesions on the copolymer films with/without drug were compared by the culture of NIH/3T3 mouse embryo fibroblasts on the surfaces. For in vivo evaluation of tissue anti-adhesion potential, the copolymer films with/without drug were implanted between the cecum and peritoneal wall defects of rats and their tissue adhesion extents were compared. It was observed that the ibuprofen-containing PLLA-PEG films with high PEG composition (particularly PLLA113-PEG113 film with PEG composition, 50 mol%) were very effective in preventing cell or tissue adhesion on the film surfaces, probably owing to the synergistic effects of highly mobile, hydrophilic PEG and anti-inflammatory drug, ibuprofen.

Abdominal Wall↗
PubMed2006

ABA and BAB type triblock copolymers of PEG and PLA: a comparative study of drug release properties and "stealth" particle characteristics.

We synthesized two types of triblock copolymers containing PEG and PLA as controlled release carriers of hydrophobic drugs: these are the ABA type (PLA-PEG-PLA) and the BAB type (PEG-PLA-PEG). These polymers are amphiphilic and can form nanomicelles (40-200nm) in aqueous medium. On the surface of PLA-PEG-PLA (ABA) type nanomicelles, the PEG content was enhanced somewhat over the bulk amount; whereas in the PEG-PLA-PEG (BAB type), surface segregation was much higher. The copolymers tested can entrap 35% of paclitaxel by weight on the average. In general, the diffusion-controlled release of paclitaxel is slower for the BAB polymers; furthermore, the actual release rates are influenced by the PLLA lengths in the BAB copolymers. Surface PEG contents influence the "stealth" characteristics of the nanomicelles. Compared with PLA particles, all nanomicellar particles tested, of both BAB and ABA types, showed a four-fold reduction in monocyte cell uptake, with the BAB type copolymer exhibiting a lesser uptake.

Delayed-Action Preparations↗
PubMed2004

Effect of hyaluronidase and PEG chain conjugation on the biologic and antitumor activity of RNase A.

Subcutaneous application of bovine RNase A conjugated to HYase (bovine hyaluronidase), polyethylene glycol (PEG) and HYase+PEG resulted in a marked reduction of the width of the spermatogenic layers of the mouse testes. The number of sperms in caput epididymidis was significantly decreased in mice injected with conjugated RNase A. There was not any significant embryotoxic effect of free RNase A even conjugated with HYse, PEG and HYse+PEG. The immunogenicity, expressed in production of antibodies against free RNase A or conjugates with PEG, was very low. However, the immunogenic action of this enzyme conjugated only to HYase was much higher and produced the same immunogenicity as HYase itself. The immunogenic effect of RNase A+HYase conjugate decreased when PEG was joined to this conjugate. The inhibitory effect of RNase A conjugated to HYase, PEG and HYase+PEG on human ML-2 cells studied in vitro, was practically ineffective. On the other side, when RNase A conjugated to HYase or PEG was administered intraperitoneally into the mice bearing human melanoma, the antitumor effect was pronounced.

Animals↗
PubMed2004

Intracellular targeting of sodium mercaptoundecahydrododecaborate (BSH) to solid tumors by transferrin-PEG liposomes, for boron neutron-capture therapy (BNCT).

The successful treatment of cancer by boron neutron-capture therapy (BNCT) requires the selective delivery of relatively high concentration of 10B compounds to malignant tumor tissue. This study focuses on a new tumor-targeting drug delivery system for BNCT that uses small (less than 200 nm in diameter), unilamellar mercaptoundecahydrododecaborate (BSH)-encapsulating, transferrin (TF)-conjugated polyethyleneglycol liposomes (TF-PEG liposomes). When TF-PEG liposomes were injected at a dose of 35 mg 10B/kg, we observed a prolonged residence time in the circulation and low uptake by the reticuloendothelial system (RES) in Colon 26 tumor-bearing mice, resulting in enhanced accumulation of 10B into the solid tumor tissue (e.g., 35.5 microg/g). TF-PEG liposomes maintained a high 10B level in the tumor, with concentrations over 30 microg/g for at least 72 h after injection. This high retention of 10B in tumor tissue indicates that binding and concomitant cellular uptake of the extravasated TF-PEG liposomes occurs by TF receptor and receptor-mediated endocytosis, respectively. On the other hand, the plasma level of 10B decreased, resulting in a tumor/plasma ratio of 6.0 at 72 h after injection. Therefore, 72 h after injection of TF-PEG liposomes was selected as the time point of BNCT treatment. Administration of BSH encapsulated in TF-PEG liposomes at a dose of 5 or 20 mg 10B/kg and irradiation with 2 x 10(12) neutrons/cm2 for 37 min produced tumor growth suppression and improved long-term survival compared with PEG liposomes, bare liposomes and free BSH. Thus, intravenous injection of TF-PEG liposomes can increase the tumor retention of 10B atoms, which were introduced by receptor-mediated endocytosis of liposomes after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation. These results suggest that BSH-encapsulating TF-PEG liposomes may be useful as a new intracellular targeting carrier in BNCT therapy for cancer.

Animals↗
PubMed2000

Effect of grafted polyethylene glycol (PEG) on the size, encapsulation efficiency and permeability of vesicles.

Liposomes have been prepared by the vesicle extrusion method (VETs) from mixtures of dipalmitoylphosphatidylcholine (DPPC), phosphatidylinositol (PI) and dipalmitoylphosphatidylethanolamine with covalently linked poly(ethylene glycol) molecular mass 5000 and 2000 (DPPE-PEG 5000 and DPPE-PEG 2000) covering a range of 0-7.5 mole%. The encapsulation of D-glucose has been studied and found to be markedly dependent on the mole% DPPE-PEG. The permeability of the liposomes to D-glucose has been measured both as a function of temperature and liposome composition. The permeability coefficients for D-glucose increase with mole% DPPE-PEG 5000 and with temperature over the range 25-50 degrees C. The activation energies for glucose permeability range from 90 to 23 kJ mol(-1). The decrease in activation energy with increasing temperature is attributed to an increasing number of bilayer defects as the liposome content of PEG-grafted lipid is increased. The dependence of D-glucose encapsulation as a function of PEG-grafted lipid content is discussed in terms of the conformation of the PEG molecules on the inner surface of the bilayer. For liposomes containing DPPE-PEG 5000 the relative percentage encapsulation of glucose, assuming that the PEG surface layer excludes glucose, is comparable to that predicted from the mushroom and brush conformational models.

1,2-Dipalmitoylphosphatidylcholine↗