Biomedical subjects

P Caliceti

Publications and source records attributed to P Caliceti.

At least 19 recordsLinked to original sources

PubMed2004

Synthesis, physico-chemical and biological characterization of a paclitaxel macromolecular prodrug.

Paclitaxel was attached to poly(hydroxyethylaspartamide) via a succinic spacer arm by a two-step protocol: (1) synthesis of 2'-O-succinyl-paclitaxel; (2) synthesis of PHEA-2'-O-succinyl-paclitaxel. The 2'-O-succinyl-paclitaxel derivative and the macromolecular conjugate were characterized by UV, IR, NMR and mass spectrometry analysis. The reaction yields were over 95% and the purity of products over 98%. Paclitaxel release and degradation from 2'-O-succinyl-paclitaxel occurred at a faster rate at pH 5.5 than 7.4. After 30 h of incubation at pH 5.5 and 7.4 the released free paclitaxel was about 40 and 20%, respectively. In plasma both drug release and degradation were found to occur at a higher rate than in buffer at pH 7.4 suggesting that an enzymatic mechanism could be involved. The paclitaxel release and degradation from PHEA-2'-O-succinyl-paclitaxel were negligible at pH 5.5 and 7.4 and very slow in plasma. Investigation carried out using murine myeloid cell line showed that the polymeric prodrug maintains partial pharmacological activity of paclitaxel. The DL50 of the conjugate (over 40 ng/ml) as compared to free paclitaxel (about 1 ng/ml) was correlated to the slow drug release. Finally a pharmacokinetic study carried out by intravenous inoculation of the macromolecular prodrug to mice demonstrated that the polymer conjugation modify dramatically the in vivo fate of the drug. The conjugate disappeared from the bloodstream much more quickly as compared to both free drug and naked polymer. Massive accumulation of bioconjugate in the liver (80% of the dose) was found to persist throughout 1 week.

Animals↗

PubMed2003

PEGylation of growth hormone-releasing hormone (GRF) analogues.

Synthetically produced GRF1-29 (Sermorelin) has an amino acid composition identical to the N-terminal 29 amino acids sequence of the natural hypothalamic GHRH1-44 (Figure 1). It maintains bioactivity in vitro and is almost equally effective in eliciting secretion of endogenous growth hormone in vivo. The main drawbacks associated with the pharmaceutical use of hGRF1-29 relate to its short half-life in plasma, about 10-20 min in humans, which is caused mostly by renal ultrafiltration and enzymatic degradation at the N terminus. PEGylation has been considered as one valid approach to obtain more stable forms of the peptide, with a longer in vivo half-life and ultimately with increased pharmacodynamic response along the somatotropic axis (endogenous GH, IGF-1 levels). Different PEGylated GRF conjugates were obtained and their bioactivity was tested in vitro and in vivo by monitoring endogenous growth hormone (GH) serum levels after intravenous (i.v.) injection in rats, and intravenous and subcutaneous (s.c.) injection in pigs. It was found that GRF-PEG conjugates are able to bind and activate the human GRF receptor, although with different potency. The effect of PEG molecular weight, number of PEG chains bound and position of PEGylation site on GRF activity were investigated. Mono-PEGylated isomers with a PEG5000 polymer chain linked to Lys 12 or Lys 21 residues, showed high biological activity in vitro, which is similar to that of hGRF1-29, and a higher pharmacodynamic response as compared to unmodified GRF molecule.

Animals↗

PubMed2002

Pretargeted adjuvant radioimmunotherapy with yttrium-90-biotin in malignant glioma patients: a pilot study.

In a previous study we applied a three-step avidin-biotin pretargeting approach to target 90Y-biotin to the tumour in patients with recurrent high grade glioma. The encouraging results obtained in this phase I-II study prompted us to apply the same approach in an adjuvant setting, to evaluate (i) time to relapse and (ii) overall survival. We enrolled 37 high grade glioma patients, 17 with grade III glioma and 20 with glioblastoma, in a controlled open non-randomized study. All patients received surgery and radiotherapy and were disease-free by neuroradiological examinations. Nineteen patients (treated) received adjuvant treatment with radioimmunotherapy. In the treated glioblastoma patients, median disease-free interval was 28 months (range=9-59); median survival was 33.5 months and one patient is still without evidence of disease. All 12 control glioblastoma patients died after a median survival from diagnosis of 8 months. In the treated grade III glioma patients median disease-free interval was 56 months (range=15-60) and survival cannot be calculated as only two, within this group, died. Three-step radioimmunotherapy promises to have an important role as adjuvant treatment in high grade gliomas, particularly in glioblastoma where it impedes progression, prolonging time to relapse and overall survival. A further randomized trial is justified.

Adult↗

PubMed2001

Synthesis and biopharmaceutical characterisation of new poly(hydroxyethylaspartamide) copolymers as drug carriers.

Four new poly(hydroxyethylaspartamide)-based copolymers bearing (a) poly(ethylene glycol) 2000, (b) poly(ethylene glycol) 5000, (c) poly(ethylene glycol) 2000 and hexadecylalkyl, (d) poly(ethylene glycol) 5000 and hexadecylalkyle, as pendant groups were synthesised. The copolymers were obtained by partial aminolysis of polysuccinimide with poly(ethylene glycol) and hexadecylalkyl amino derivatives followed by reaction with ethanolamine. Naked polyhydroxyaspartamide was obtained by polysuccinimide reaction with ethanolamine. The nuclear magnetic resonance, infrared, light scattering and elemental analysis allowed for the extensive physico-chemical characterisation of the carriers. The molecular mass of all the polymers was in the range of 27000-34000 Da, and the polydispersivity was in the range of 1.5-1.7. By intravenous injection to mice bearing a solid tumour, all the polymeric carriers displayed a bi-compartmental pharmacokinetic behaviour. Both the poly(ethylene glycol) and the hexadecylalkyle conjugation prolonged and enhanced the distribution phase of poly(hydroxyethylaspartamide). The poly(ethylene glycol) conjugation was found to promote the carrier elimination by kidney ultrafiltration and to prevent partially the accumulation in the spleen and in the liver. The poly(ethylene glycol)/hexadecylalkyle conjugates localised preferentially in the liver were over 30% of the dose/g of tissue was determined after 144 h from administration. In the tumour all the polymers displayed a relevant accumulation that significantly increased throughout the time to reach high concentrations after 24 h. In particular, the poly(ethylene glycol)/hexadecylalkyle conjugates achieved a concentration of 15-25% of the dose/g of tissue after 24 h from administration that was maintained up to 144 h.

Animals↗

PubMed2001

Controlled release of biomolecules from temperature-sensitive hydrogels prepared by radiation polymerization.

Poly(acryloyl-L-proline methyl ester)-based hydrogels containing 1 and 5% of a crosslinking agent were studied as drug delivery systems. The drug loading properties were investigated by matrix incubation into solutions containing biomolecules with molecular weight ranging between 300 and 65,000 Da. The loading yield was found to depend on both the crosslinking degree and the molecular weight of the drug. In vitro release studies were carried out with both swollen and dry matrices loaded with gentamicin, isoniazid and insulin. Gentamicin and isoniazid were released by a bimodal Fickian diffusion with a remarkable burst that was found to depend on both matrix crosslinking degree and physical state. In vivo, the subcutaneous implantation into mice of the isoniazid loaded matrices allowed for an efficient drug release for 800 h. In vitro insulin was released from the swollen matrices for 1500 h by diffusional Fickian mechanism while the dry ones displayed a lag time followed by Fickian diffusion release. The subcutaneous implantation of the insulin-loaded matrices into diabetic mice induced a remarkable decrease in the glucose concentrations in blood. In particular, the dry 1% matrices were found to maintain a low glucose level for 700 h.

Animals↗

PubMed2001

Production of insulin-loaded poly(ethylene glycol)/poly(l-lactide) (PEG/PLA) nanoparticles by gas antisolvent techniques.

Insulin and insulin/poly(ethylene glycol) (PEG)-loaded poly(l-lactide) (PLA) nanoparticles were produced by gas antisolvent (GAS) CO(2) precipitation starting from homogeneous polymer/protein organic solvent solutions. Different amounts of PEG 6000 (0, 10, 30, 50, 100, and 200% PEG/PLA w/w) or concentration of 30% PEG/PLA with PEGs with different molecular weight (MW; 350, 750, 1900, 6000, 10,000, and 20,000) were used in the preparations. The process resulted in high product yield, extensive organic solvent elimination, and maintenance of > 80% of the insulin hypoglycemic activity. Nanospheres with smooth surface and compact internal structure were observed by scanning electron microscopy. The nanospheres presented a mean particle diameter in the range 400-600 nm and narrow distribution profiles. More than 90% of drug and PEG were trapped in the PLA nanoparticles when low MW PEGs were used in the formulation, whereas the addition of high MW PEGs significantly reduced the loading yield. In all cases, in vitro release studies showed that only a little amount of drug was released from the preparations. However, formulations containing low MW PEGs allowed for a slow but constant drug release throughout 1500 h, whereas a burst was obtained by increasing the PEG MW. In conclusion, the GAS process offers a mean to produce protein-loaded nanoparticles possessing the prerequisites for pharmaceutical applications. The PEG added to the formulation was found to play a key role in the simultaneous solute precipitation phenomena and in determining the release behavior and the chemical-physical properties of the formulation.

Animals↗

PubMed2001

Calcitonin release system in the treatment of experimental osteoporosis. Histomorphometric evaluation.

Bioabsorbable polyphosphazene matrices charged with 250 microg calcitonin were evaluated as calcitonin delivery systems for the controlled release of this drug in an in vivo experimental model. Matrices were implanted under general anesthesia in osteopenic female rats, while a group of osteopenic animals (control group) received unloaded matrices. After 30 days a second series of matrices, loaded and unloaded was, respectively, implanted in both groups. In a third group of osteopenic female rats (positive control), 10 IU calcitonin were injected daily for two months. A baseline group and a sham operated group of animals were also included in the study. The explanted matrices were histologically evaluated together with the surrounding tissues, and bone histomorphometry was performed on undecalcified sections from femurs. The results showed the good biocompatibility of the matrices. Bone histomorphometry revealed that bone architecture in the treatment group was improved and results were not different from those observed after calcitonin injection. These data confirm a good in vivo behavior of the system, as well as a therapeutic effect of the released calcitonin in the osteopenic condition.

Animals↗

PubMed2001

Pre-targeted locoregional radioimmunotherapy with 90Y-biotin in glioma patients: phase I study and preliminary therapeutic results.

The aim of this study was to determine the maximum-tolerated dose, of a pre-targeting three-step (3-S) method employing 90Y-biotin in the locoregional radioimmunotherapy (RIT) of recurrent high grade glioma, and to investigate the antitumor efficacy of this new treatment. Twenty-four patients with recurrent glioma underwent second surgical debulking and implantation of a catheter into the surgical resection cavity (SRC), in order to introduce the radioimmunotherapeutic agents [biotinylated monoclonal antibody (MoAb), avidin and 90Y-biotin]. Eight patients with anaplastic astrocytoma (AA) and 16 patients with glioblastoma (GBM) were injected with biotinylated anti-tenascin MoAb (2 mg), then with avidin (10 mg; 24 h later) and finally 90Y-biotin (18 h later). Each patient received two of these treatments 8-10 weeks apart. The injected activity ranged from 0.555 to 1.110 GBq (15-30 mCi). Dosage was escalated by 0.185 GBq (5 mCi) in four consecutive groups. The treatment was well tolerated without acute side effects up to 0.740 GBq (20 mCi). The maximum tolerated activity was 1.110 GBq (30 mCi) limited by neurological toxicity. None of the patients developed hematologic toxicity. In three patients infection occurred around the catheter. The average absorbed dose to the normal brain was minimal compared with that received at the SRC interface. At first control (after 2 months), partial (PR) and minor (MR) responses were observed in three GBM (1 PR; 2 MR) and three AA patients (1 PR; 2 MR) with an overall objective response rate of 25%. Stable disease (SD) was achieved in seven GBM and five AA patients (50%). There was disease progression in six GBM patients (25%), but in none of the AA patients. At the dosage of 0.7-0.9 GBq per cycle, locoregional 3-S-RIT was safe and produced an objective response in 25% of patients. Based on these encouraging results, phase II studies employing 3-S-RIT soon after first debulking are justified.

Adult↗

PubMed2000

Polyphosphazene microspheres for insulin delivery.

Polyphosphazene based microspheres for insulin delivery were prepared following three different procedures: (A) suspension-solvent evaporation; (B) double emulsion-solvent evaporation; (C) suspension/double emulsion-solvent evaporation. Methods A and C allowed for higher protein loading than procedure B. Scanning electron microscopy showed that all preparation procedures achieve microparticles with spherical shape, porous surface and internal honeycomb structure. In all cases insulin was released 'in vitro' by a bi-modal behaviour: fast release during the first 2 hours followed by a slow release. However, both the physical properties and the 'in vitro' release profiles were found to depend upon the preparation conditions. Subcutaneous administration to diabetic mice of microspheres obtained with methods A and C rapidly reduced the glucose levels of about 80% but most of activity was lost in 100 hours. Both preparations B induced a remarkable decrease in glucose levels and the activity was maintained throughout 1000 h. Finally all preparations stimulated anti-insulin antibody production that constantly increased over a period of 8 weeks.

Animals↗

PubMed2000

Therapeutic proteins: a comparison of chemical and biological properties of uricase conjugated to linear or branched poly(ethylene glycol) and poly(N-acryloylmorpholine).

Uricase from Bacillus fastidiosus (UC) was covalently linked to linear PEG (PEG-1) (Mw 5 kDa), branched PEG (PEG-2) (Mw 10 kDa) and to poly(N-acryloylmorpholine) (PAcM) (Mw 6 kDa). The conjugation of UC with linear PEG and PAcM was accompanied by complete loss of enzymatic activity but, if uric acid as site protecting agent was included in the reaction mixture, the conjugate protein retained enzymatic activity. On the other hand, the modification with PEG-2 gave a conjugate that also maintained enzymatic activity in the absence of any active site protection. This behaviour must be related to hindrance of the branched polymer in reaching the enzyme active site. The UC conjugates exhibited increased resistance to proteolytic digestion while minor variations in the inhibitory constant, optimal pH, heat stability, affinity for substrate, were observed. Pharmacokinetic investigations in mice demonstrated increased residence time in blood for all the conjugates as compared with native uricase. Uricase conjugated with linear PEG was longer lasting in blood UC derivative, followed by branched PEG and the PAcM conjugates. Unconjugated uricase was rapidly removed from circulation. All these data are in favour of the use of the less known amphiphilic polymer PAcM as an alternative to PEGs in modification of enzymes devised for therapeutic applications.

Acrylic Resins↗

PubMed2000

Design and in vivo evaluation of an oral delivery system for insulin.

PURPOSE: To develop an oral controlled release system for insulin. METHODS: The polymer-inhibitor conjugates carboxymethylcellulose (CMC)-Bowman-Birk inhibitor and CMC-elastatinal were homogenized with polycarbophil-cysteine conjugate, insulin, and mannitol, compressed to 2 mg microtablets and enteric coated with a polymethacrylate. The protective effect of this delivery system for insulin towards enzymatic degradation, as well as the release profile, was evaluated in vitro. In addition, the effect of the dosage form on glucose levels of diabetic mice was determined. RESULTS: Tablets containing the CMC-inhibitor conjugates showed a strong protective effect for insulin. Whereas 91.6 +/- 7.4% (mean +/- SD, n = 3) of insulin in the dosage form without the inhibitor conjugates has been degraded within 3 h of incubation in an artificial intestinal fluid containing physiological concentrations of trypsin, chymotrypsin, and elastase, 49.7 +/- 5.5% (mean +/- SD, n = 3) of insulin remained stable in the delivery system containing the polymer-inhibitor conjugates. Additionally, polycarbophil-cysteine (PCP-Cys) provides high cohesiveness of the dosage form, due to the formation of interas well as intramolecular disulfide bonds within the polymer matrix. According to this, a controlled release of insulin could be achieved over a time period of 10 h. Furthermore, in vivo studies in diabetic mice showed a decrease in basal glucose levels of 20% to 40% during a time period of 80 h. CONCLUSIONS: Mucoadhesive polymer-inhibitor conjugates might represent a promising excipient in delivery systems for oral (poly)peptide delivery.

Acrylic Resins↗

PubMed2000

Plain and drug loaded polyphosphazene membranes and microspheres in the treatment of rabbit bone defects.

The healing of periodontal surgical defects was studied in rabbits, using polyphosphazenes (POP) membranes and microspheres, both plain or drug-enriched. POP polymers having amino acid ester as backbone substituents, are used since they resorb and undergo hydrolytic degradation to ammonia, phosphate and amino acids. Fourteen animal were operated in tibia, and other fourteen at angle of the mandible, that was reached by extraoral access. Bone defects were performed in tibiae, and covered either with POP or with poly-tetrafluoroethylene (PTFE) membranes, while other rabbits served as controls. The animals were sacrificed after one and two months, and the tibiae taken and processed for optical microscopy. Similar surgical defects were made in mandible, and POP membranes were placed over the breaches, some of which were filled with POP microspheres, both alone or mixed with granular hydroxyapatite. For comparison, two rabbits were treated with PTFE membranes, while other two served as controls. The animals operated at the mandible were all sacrificed after one month, and the operated bones taken and processed for histology. It was found that POP membranes were very effective in promoting the healing in tibiae, while less satisfactory results were found in the animals treated with PTFE membranes and in controls. In mandible, the healing occurred without a clear relationship with the grafted microgranular material or the membrane, since repairing bone was found also in controls. In any case, both POP membranes and microspheres showed excellent biocompatibility, as no inflammatory cells or macrophages were found in the surrounding tissue. This property was completely independent from the presence of drug, since the matrix-entrapped drugs, released in the tissue, did not hamper the bone healing. It was also found that POP, by itself, has a positive effect in stimulating the bone repair.

Journal Article↗

PubMed1999

Immunogenic and tolerogenic properties of monomethoxypoly(ethylene glycol) conjugated proteins.

An immunogenic and tolerogenic characterisation of monomethoxypoly(ethylene glycol) conjugated proteins was carried out using, as immunogen models, an anti-malaria chimera monoclonal antibody (PfChMab) and a macrophage colony stimulating factor (M-CSF). Two conjugates of PfChMab were prepared by polymer derivatisation of 19 and 33% protein amino groups and one conjugate of M-CSF was obtained by modification of 24% amino groups. In mice M-CSF was found to elicit rapidly high IgG and IgM levels whereas the monomethoxypoly(ethylene glycol) derivatised M-CSF stimulated a significantly lower immunoresponse. Native PfChMab was found to induce a delayed immunoresponse with high IgM levels but low production of IgG. Furthermore, similar immunogenic profiles were obtained with the native and modified protein forms. The pre-administration of polymer conjugated M-CSF to mice subsequently treated with the native protein was found to suppress up to 75% of anti-native M-CSF IgG, while IgM production was not affected. On the other hand the pre-administration of monomethoxypoly(ethylene glycol) derivatised PfChMab was found to reduce significantly the generation of anti-native PfChMab IgM. Such suppression depended on the degree of modification: the conjugate with the higher number of polymer chains was more effective in suppressing the immunoresponse.

Animals↗

PubMed1999

Polyphosphazene membranes and microspheres in periodontal diseases and implant surgery.

Membranes or microcapsules made from polyphosphazenes bearing amino acid side groups are proposed for the treatment of periodontal diseases. Polyphosphazene membranes, prepared with alanine ethyl ester and imidazole in the molar ratio of 80:20 as phosphorus substituents, gave a degradation rate that corresponded to the healing of the bone defect. These membranes were much more successful in promoting healing of rabbit tibia defects than polytetrafluoroethylene membranes. Antibacterial or anti-inflammatory drugs, useful in periodontal tissue regeneration, could be entrapped in the polyphosphazene membranes and released both in vitro and in vivo at a rate that ensured therapeutic concentrations in the surrounding tissue. Polyphosphazene microspheres, prepared with phenylalanine ethyl ester as a phosphorus substituent and loaded with succinylsulphathiazole or naproxen, were also obtained. The kinetics of release from these matrices were very convenient in yielding local concentrations of the two drugs that are useful per se or when mixed with hydroxyapatite for better bone formation.

Animals↗

PubMed1998

Polyorganophosphazene microspheres for drug release: polymer synthesis, microsphere preparation, in vitro and in vivo naproxen release.

Microsphere preparation for naproxen slow release was investigated using two newly prepared biodegradable polyorganophosphazenes, derivatized at the phosphorus atoms with phenylalanine ethyl ester and imidazole at molar ratios of 71/29 and 80/20. The polymers were prepared by substitution of the chloride atoms of polydichlorophosphazene with a phenylalanine ethyl ester-imidazole mixture followed, after 7 or 48 h reaction, by the addition of excess imidazole. Three methods of microsphere preparation have been considered: spray-drying, emulsion/solvent evaporation and emulsion/solvent evaporation-extraction. Microparticles obtained by spray-drying were found to possess a narrow distribution size with a mean diameter of 2-5 microm. Their internal structure consisted of a porous or empty core depending upon the solvent used for the preparation. Furthermore the microspheres prepared with this technique rapidly released the entrapped naproxen independently of the used polymer, the drug loading or the preparation process. On the other hand microspheres prepared by solvent evaporation or solvent evaporation-extraction showed a distribution size ranging between 10 and 100 microm. By the appropriate choice of pH and solvent composition of the external phase, naproxen could be entrapped, in these microspheres, with a yield higher of 80%. The polymer composition dictates the in vitro release rate of naproxen from the particles, which was faster when the microspheres were prepared with the polymer at higher imidazole content. In vivo experiments, carried out by subcutaneous implantation in rats of microspheres prepared by solvent evaporation, demonstrated that a constant level of naproxen in plasma could be maintained up to 400 h at a suitable concentration for antinflammatory activity.

Animals↗

PubMed1998

Biochemical modifications of avidin improve pharmacokinetics and biodistribution, and reduce immunogenicity.

Pretargeting techniques using the avidin-biotin system have shown encouraging results in both diagnostic and therapeutic clinical trials. It has been shown that in cancer therapy the ideal agent to be used for pretargeting should have a plasma half-life longer than avidin and lower immunogenicity than streptavidin in order for these procedures to be applied safely and repeatedly in patients. We prepared a recombinant form of avidin with no carbohydrates and avidins, biochemically modified either by decreasing the positive charges with succinic anhydride or by linking polyethylene glycol (PEG) at three different molar ratios and evaluated their in vivo behaviour after i.p. administration in mice. The succinylation and PEGylation of avidin increased the plasma half-life proportionally to the degree of protein modification. The procedures, however, affected the biotin binding to some extent. The biodistribution studies showed that, for all six time points (ranging from 20 min to 18 h post-injection), the liver and kidney to blood ratios were lower for PEGylated avidins than native, recombinant and succinyl avidin. Recombinant and low PEGylated avidin evoked an immune response in all mice after at least three injections. Native, recombinant and succinyl avidins showed higher serum titres than PEGylated avidins. In conclusion, the conjugation of avidin to PEG chains (n = 7) originates a compound with a suitable blood clearance, low immunogenicity and concurrent low cross-reactivity with avidin.

Animals↗

PubMed1997

Bioabsorbable polyphosphazene matrices as systems for calcitonin controlled release.

To provide a suitable delivery system for the calcitonin controlled release 80 mg bioabsorbable polyphosphazene matrices were obtained with entrapped 50 or 250 micrograms calcitonin. The in vitro behaviour demonstrated a release burst for about 24 hours, followed by a period of slow release of the peptide lasting for weeks. Matrices containing 250 micrograms calcitonin were implanted under general anaesthesia in osteoporotic female rats, while a group of animals (control group) received unloaded matrices. After thirty days a second batch of matrices was implanted in both groups to prolong the period of treatment until two months. The explanted matrices were histologically evaluated together with the surrounding tissues, and the dosage of the residual calcitonin was also performed. Results demonstrated the good biocompatibility of the system and the complete release of the calcitonin from the matrices 30 days after implantation. The therapeutic effect, after sixty days of treatment was confirmed by the better densitometric values observed in the femoral bone of treated animals than in controls.

Animals↗

PubMed1996

Protective effect of superoxide dismutase and polyethylene glycol-linked superoxide dismutase against renal warm ischemia/reperfusion injury.

The protective effect of oxygen free radical scavenger superoxide dismutase (SOD) against the warm ischemic damage that occurs in kidneys harvested from non-heart-beating donors is controversial because of its short half-life. In this model, we compared the protective effect of SOD and two longer lasting polyethylene glycol (PEG)-linked forms of SOD in a model of renal ischemia induced by 60 min of arterial clamping in rats. Rats treated with PEG1-SOD and PEG2-SOD had a better renal function than controls, with significantly lower serum creatinine levels throughout the follow-up period and a significantly higher creatinine clearance on postoperative days 1, 2, and 4. In native SOD treated-rats, serum creatinine was lower than in controls, though not significantly so, and creatinine clearance was significantly higher on postoperative day 4. Our results indicate that the protective effect of SOD against renal warm ischemia can be enhanced by prolonging its half-life by binding the enzyme to PEG.

Animals↗