Biomedical subjects

Ping Peng

Publications and source records attributed to Ping Peng.

At least 19 recordsLinked to original sources

PubMed2006

Thin calcium phosphate coatings on titanium by electrochemical deposition in modified simulated body fluid.

Adherent and optically semitransparent thin calcium phosphate (CaP) films were electrochemically deposited on titanium substrates in a modified simulated body fluid at 37 degrees C. Coatings deposited by using periodic pulsed potentials showed better adhesion and better mechanical properties than coatings deposited with use of a constant potential. Scanning electron microscopy was used to study the morphology of the coatings. The coatings displayed a polydispersed porous structure with pores in the range of a few nanometers to 1 mum. Furthermore, X-ray diffractometry and the O(1s) satellite peaks in X-ray photoelectron spectroscopy indicated that the coatings possessed a similar surface chemistry to that of natural bone minerals. These results were confirmed by inductively coupled plasma optical emission spectrometry, which yielded a Ca:P ratio of 1.65, close to that of hydroxyapatite. Contact mode atomic force microscopy (AFM) showed the average thickness of the coatings was in the order of 200 nm. Root-mean-square (RMS) roughness values, also derived by AFM, were shown to be much higher on the titanium-CaP surfaces in comparison with untreated titanium substrates, with RMS values of about 300 and 110 nm, respectively. Cell culture experiments showed that the CaP surfaces are nontoxic to MG63 osteoblastic cells in vitro and were able to support cell growth for up to 4 days, outperforming the untreated titanium surface in a direct comparison. These easily prepared coatings show promise for hard-tissue biomaterials.

Adhesiveness↗

PubMed2006

[Primary study on fusions of ovarian carcinoma cells to dendritic cell transfected with interleukin-12 gene in vitro].

OBJECTIVE: To investigate the immune response of the fusions of ovarian carcinoma cells to dendritic cell (DC) transfected with interleukin (IL)-12 gene in vitro. METHODS: Recombinant human granulocyte macrophage colony stimulating factor and recombinant human tumor necrosis factor alpha were used to generate DC from cord blood in vitro. IL-12 fusion gene was cloned into a eukaryotic vector-pcDNA3.1 (+). DC were transfected with IL-12-pcDNA3.1 (+) using lipofectamine transfection method and electric transfection method respectively. Then polyethylene glycol mediated the fusion of transfected DC and ovarian carcinoma cells, and 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) test was carried out to observe the immune response. RESULTS: DC were generated in vitro from cord blood and expressed high levels of costimulatory (50%) and MHC II molecules (99%). RT-PCR showed that IL-12-pcDNA3.1 (+) had been successfully transfected into DC. RT-PCR and immunofluorescence analysis showed that DC were fused with ovarian carcinoma cells successfully. Then the fusion cells of ovarian carcinoma cells to transfected DC, and the fusions of ovarian carcinoma cells to DC were cocultured with peripheral blood mononuclear cell respectively. MTT test showed that both fusions could induce cytolytic T cell activity and lysis of ovarian carcinoma cells, and the former effect was stronger. CONCLUSION: The cytolytic T cell activity induced by the fusions of ovarian carcinoma cells to transfected DC is enhanced.

Cell Fusion↗

PubMed2005

Antitumor activity of poly(ethylene glycol)-camptothecin conjugate: the inhibition of tumor growth in vivo.

Antitumor effect of poly(ethylene glycol)-camptothecin conjugate (PEG-CPT) was studied in the nude mouse model of human colon cancer xenografts. The animals were treated intravenously with 15 mg/kg of camptothecin (CPT) or PEG-CPT conjugate at equivalent CPT dose. Antitumor activity, apoptosis induction and caspase-dependent signaling pathways were studied 12, 24, 48 and 96 h after single injection. In addition, pharmacokinetics, tumor distribution and accumulation of PEG polymer labeled with green fluorescence protein (GFP) were studied. The data obtained showed that the conjugation of low molecular weight anticancer drug CPT with low solubility to high molecular weight water-soluble PEG polymer provides several advantages over the native drug. First, the conjugation improves drug pharmacokinetics in the blood and tumor. Second, such conjugation provides passive tumor targeting by the Enhanced Permeability and Retention (EPR) effect, increasing drug concentration in the tumor. Third, the coupling increases the bioavailability of CPT, induces apoptosis in tumor and, therefore, enhances anticancer activity of PEG-CPT. Thus, the use of macromolecular conjugate provided passive tumor targeting of the drug, improved pharmacokinetics and increased the stability of the drug during circulation. It offered better uptake by the targeted tumor cells and substantially enhanced apoptosis and antitumor activity of the conjugated drug in the tumor and decreased apoptosis in liver and kidney as compared with the native drug. All these characteristics make PEG-CPT conjugate an attractive anticancer drug for the effective chemotherapy of solid tumors.

Animals↗

PubMed2005

An unexpected amide bond cleavage: poly (ethylene glycol) transport forms of vancomycin. 2.

PEG-amide vancomycin derivatives (V(3) position) have been synthesized and found to behave as prodrugs in vivo, demonstrating anti-microbial activity in mice when challenged with Staphylococcus aureus. The corresponding PEG-carbamate derivatives do not manifest this in vivo activity, although both classes of compounds have similar in vitro rat plasma stability. Thus, it appears that extra vascular cleavage of the amide bond can occur if the condition of extended circulation of the conjugate is met, resulting in the release of vancomycin.

Amides↗

PubMed2005

[Cloning and expression of the alpha-amylase gene from a Bacillus sp. WS06, and characterization of the enzyme].

A Bacillus sp. WS06, which produces an extracellular alpha-amylase, was isolated from the cecum in a piglet. An amyF gene from this Bacillus strain was cloned and its nucleotide sequence was determined. An open reading frame composed of 1581 bases, which encodes 526 amino acid residues was found. The amyF gene shows high sequence homologies with other microbial amylase genes, such as Bacillus megaterium and Bacillus polymyxa (93% and 53% identity). The deduced amino acid sequence revealed that four highly conserved regions of the alpha-amylase family. The amyF gene was overepressed using the pET21a vector and Escherichia coli BL21 (DE3). The recombinant enzyme was purified 22.2 fold to electrophoretic homogeneity and had a molecular mass of 57kD (by SDS-PAGE). The enzyme was optimally active at pH 7 and 55 approximately 60 degrees C and showed stability at the temperature below 55 degrees C. This enzyme efficiently hydrolyzed various types of starch to yield a series of malto-oligosaccharides by endo-cleavage mode.

Animals↗

PubMed2004

[Cytotoxicity of MICA-reactive V delta 1 gamma delta T cells towards epithelial tumor cells].

OBJECTIVE: To confirm whether human MHC class I chain-related A (MICA) induces the amplification of V delta 1 gamma delta tumor-infiltrating lymphocytes (TILs) in vitro and to identify the cytotoxicity of MICA-reactive V delta 1 gamma delta TILs towards epithelial tumor cells. METHODS: MICA protein was prokaryoticly expressed and purified by molecular cloning technology. The purified recombined MICA (rMICA) was used to induce V delta 1 gamma delta T cells from tumor tissues in vitro and the cytotoxicity of these V delta 1 gamma delta TILs were tested by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). RESULTS: The rMICA was expressed in prokaryocyte with pET30 as a vector. The immobilized rMICA protein could markedly induce the amplification of V delta 1 gamma delta T cells from tumor tissue in vitro. These V delta 1 gamma delta T cells showed strong cytolytic activities towards tumor cell lines expressing MICA. CONCLUSION: The MICA-reactive V delta 1 gamma delta T cell may be a candidate for adoptive cellular therapy of tumors.

Adult↗

PubMed2004

[Hemorheological changes in hot and humid environment].

OBJECTIVE: To observe the changes in hemorheology of human under hot and humid environment. METHODS: Ninety soldiers serving in the Nansha Islands were divided into veteran group, recruit group and urapidil-treated recruit group, all of whom were required to complete 3 000-meter running exercise in 20 min in hot and humid environment. Their hemorheology were examined before and after the exercise. RESULTS: There were significant difference in the hemorheology between the 3 groups (P<0.05) both before and after the exercise, and the changes were most obvious in the veteran group followed by the new recruit group and urapidil-treated recruit group. No significant differences in the plasma indexes were detected between the 3 groups. CONCLUSIONS: Hot and humid environment causes obvious changes in the hemorheology, for which veterans and recruits have different tolerances and adaptabilities. Uradipil may help lower the magnitude of the the hemorheological changes after exercise by reducing body metabolism.

Adult↗

PubMed2004

[Establishment of canine models of penetrating craniocerebral gunshot wound].

OBJECTIVE: To establish a canine model of penetrating craniocerebral gunshot wound. METHOD: Gunshot wound was induced in 54 cross-bred dogs using 7.62-mm pistol bullets fired using a pistol from a distance of 30 cm in coronal direction with a tilt of 10 degrees toward the orbit, causing penetrating craniocerebral injury 1 cm posterior and 1.5 cm superior to the lateral canthus. The breathing and pathological changes in the brain tissue were observed after the injury. RESULTS: Autonomous breathing was recovered in 9 out of 21 dogs with respiratory arrest after the injury, and the total survival rate was 77.8% in the 54 dogs after the injury. Intracranial hematoma, intracranial pneumatosis, contusion and laceration of brain, and cranial bone fragments were found by cranial CT, with the entrance and exit of the bullet seen on the right and left frontal bone respectively. Pathological examination showed contusion and laceration of the brain tissues. CONCLUSION: The model of craniocerebral perforating wound has been successfully established in dogs.

Animals↗

PubMed2003

Tailoring structure-function and pharmacokinetic properties of single-chain Fv proteins by site-specific PEGylation.

The utility of single-chain Fv proteins as therapeutic agents would be realized if the circulating lives of these minimal antigen-binding polypeptides could be both prolonged and adjustable. We have developed a general strategy for creating tailored monoPEGylated single-chain antibodies. Free cysteine residues were engineered in an anti-TNF-alpha scFv at the C-terminus or within the linker segments of both scFv orientations, V(L)-linker-V(H) and V(H)-linker-V(L). High-level expression of 10 designed variant scFv proteins in Pichia pastoris allowed rapid purification. Optimization of site-specific conjugate preparation with 5, 20 and 40 kDa maleimide-PEG polymers was achieved and a comparison of the structural and functional properties of the scFv proteins and their PEGylated counterparts was performed. Peptide mapping and MALDI-TOF mass spectrometric analysis confirmed the unique attachment site for each PEG polymer. Independent biochemical and bioactivity analyses, including binding affinities and kinetics, antigenicity, flow cytometric profiling and cell cytotoxicity rescue, demonstrated that the functional activities of the 10 designed scFv conjugates are maintained, while scFv activity variations between these alternative assays can be correlated with conjugate and analytical designs. Pharmacokinetic studies of the PEGylated scFv in mice demonstrated up to 100-fold prolongation of circulating lives, in a range comparable to clinical antibodies.

Animals↗

PubMed2003

Temporal lobe epilepsy surgery and preoperative factors predictive of postoperative outcome: retrospective analysis of 143 cases.

OBJECTIVE: To evaluate the long-term outcome of temporal lobe epilepsy (TLE) surgery with dipole localization and to analyze the preoperative factors predicting a satisfactory postoperative outcome of the patients. METHODS: A total of 143 patients, who underwent TLE surgery with dipole localization combined with magnetic resonance imaging between 1999 and 2001 and were followed up for at least 1 year, were enrolled in this retrospective analysis of clinical, electrophysiological, neuroimaging and surgical factors to determine the independent predictors for the clinical outcome of the patients. RESULTS: During the follow-up with a mean duration of 27.5 months, 70.6% (101) of the patients were found to be completely seizure- free or with only aura (Class I), and 14.0% (20) had only rare seizures (Class II, fewer than three seizures per year), which resulted in satisfactory seizure control in 84.6% of the cases. In addition, obvious improvement was achieved in 10.5% (15) of the cases (Class III, at least an 75% seizure reduction), while 4.9% (n=7) failed to respond to the surgical treatment (Class III, less than 75% seizure reduction), showing a rate of unsatisfactory seizure control of 15.4%. The preoperative factors contributing to the prediction of good seizure control (P <0.05) included early onset of epilepsy (before the age of five years), presence of complex partial seizure as a predominant seizure type, low seizure frequency, unilateral structural abnormality detectable on magnetic resonance images, absence of cortical dysplasia, restrained epileptic activity as detected by dipole localization, and agreement of pathological findings of the lesion with epileptogenic focus. CONCLUSION: The surgical treatment with the help of dipole localization results in satisfactory clinical outcome of the patients, and some preoperative factors in relation to the clinical findings and diagnosis may predict excellent postoperative outcome.

Electroencephalography↗

PubMed2003

Dipole localization in surgical treatment of epileptic foci secondary to intracranial mass lesions: retrospective analysis of 47 cases.

OBJECTIVE: To assess the value of dipole localization in the surgical treatment of epileptic foci arising from intracranial mass lesions and observe the long-term effect of this technique. METHOD: With the assistance if dipole localization system for epileptic foci and magnetic resonance imaging (MRI), we performed precise localization of the epileptic foci secondary to the intracranial mass lesions both preoperatively and during the surgeries in 47 cases. The clinical features of this type of epilepsy and the precautions essential for the operations were reviewed, with the long-term outcome of the patients analyzed on the basis of a follow-up study for at least 1 year of all these cases. RESULTS: The mean follow-up duration was 27.9 months. After the operations, 35 patients (74.5%) were completely seizure-free or with only postoperative auras, and 7 (14.9%) had only rare fits of seizures (fewer than 3 in a year), accounting for a rate for satisfactory seizure control of 89.4% and a rate for obvious improvement of 6.4% (n=3, with at least an 75% seizure reduction). Only 2 patients (4.3%) failed to respond favorably to the surgery by showing less than 75% seizure reduction. No severe long-term complications were found in these cases. CONCLUSION: Dipole localization is capable of accurate localization of the secondary epileptic foci to provide precise guidance for their surgical treatment, with which improvement of the therapeutic effect and reduction of the complications can be achieved.

Adolescent↗

PubMed2002

Serum leptin levels of menopausal women before and after hormone replacement therapy.

OBJECTIVE: To measure serum leptin levels of menopausal women before and after hormone replacement therapy, and to evaluate the action of hormone replacement therapy in regulating serum leptin levels. METHODS: Serum leptin levels of 27 menopausal women were measured before and after hormone replacement therapy by double-antibody enzyme-linked immunosorbent assay (ELISA) and compared with those measured in 35 women with regular menstrual cycle. RESULTS: Compared with normal control (17.11+/-1.24 ng/ml), menopausal women showed significant higher mean serum leptin levels (20.75+/-2.80 ng/ml, P<0.01). After hormone replacement therapy for 6 months, serum leptin levels in these women declined to (17.46+/-1.71 ng/ml), similar to the leptin levels of normal control (P>0.05). CONCLUSION: Serum leptin levels are significantly higher in menopausal women than in women with regular menstrual cycle, and can be down-regulated by hormone replacement therapy. It is suggested that serum leptin levels might be used as an indicator to evaluate the effect of hormone replacement therapy in menopausal women.

Estrogen Replacement Therapy↗

PubMed2002

[Examining consecutively serum leptin levels in normal pregnant and pregnancy-induced hypertension women].

OBJECTIVE: To detect successsively serum leptin levels in normal, pregnancy-induced hypertension (PIH) pregnant women. METHODS: Levels of serum leptin were measured in the 16-20, 24-28, 32-36 weeks of gestation, at the delivery time in 50 healthy, 14 PIH pregnant women and their newborns and in 40 healthy non-pregnant women by Immuno-radioassay method. Serum leptin levels were correlated with body weight, body mass index (BMI), blood pressure and placental weight. RESULTS: (1) The serum leptin levels were increased gradually during the normal (14.1 +/- 2.2)-(25.4 +/- 2.7) micro g/L and the PIH pregnancy [(13.4 +/- 3.0)-(21.4 +/- 3.7)] micro g/L, especially in the PIH women. It was found that leptin concentrations rose markedly from 28 to 36 weeks of gestation, but increased slightly before the 28 weeks of gestation and after the 36 weeks of gestation in normals, and in contrast to the normal pregnancy, consistently higher until to the delivery time in the PIH. (2) The positive correlations were significant between the levels of serum leptin with their body weight and BMI in the normal pregnant and non-pregnant women (r = 0.478-0.639, P < 0.05 or P < 0.01), but not significant in the PIH pregnant (r = 0.035-0.379, P > 0.05). (3) The positive correlations were significant between the serum leptin concentrations and the systolic blood pressure, diastolic blood pressure and mean artery pressure in the PIH women after 20 weeks of gestation (r = 0.639-0.852, P < 0.05), but not significant in the normal pregnant, the PIH before 20 weeks of gestation and the non-pregnant women (r = 0.113-0.498, P > 0.05). (4) Before the delivery time, the positive correlation between the serum leptin concentrations of the pregnant women and that of the newborns was not significant, and also not significant between the puerperas' serum leptin levels and the placental weight in the normal pregnant (r = 0.132, 0.097, P > 0.05). But it was interesting that significant positive correlation was found between the puerperas' serum leptin concentrations and the cord serum leptin levels (r = 0.792, P < 0.01) and significant negative correlation was detected between the puerperas' serum leptin levels and the placental weight in the PIH women (r = -0.819, P < 0.01). (5) The leptin levels of cord blood were positively correlated with the body weight and BMI of newborns in both of the normal and PIH pregnancy (r = 0.520-0.655, P < 0.05 or P < 0.01). CONCLUSION: The characteristic change of serum leptin levels and correlations between the serum leptin concentrations and the related pregnant signs was different in normal and PIH pregnancy.

Blood Pressure↗

PubMed2002

Clinical analysis of 4 cases of juvenile granulosa cell tumor of the ovary.

OBJECTIVE: To review the diagnosis, treatment and prognosis of juvenile granulosa cell tumor of the ovary (JGCT). METHODS: To review four patients with JGCT treated in Peking Union Medical College Hospital from 1983 to 2002. RESULTS: JGCT is rare and most of the patients are adolescent or children. Solid pelvic mass with ascites and pleural effusion were mainly clinical feature. The levels of estrogen of the four patients were normal. Diagnoses were made by pathology. All 4 patients were at stage I and treated with surgery and combined chemotherapy. Two patients with high mitotic index progressed and died after 10 and 14 months, and the others without high mitotic index obtained a complete remission for 25 and 32 months. CONCLUSIONS: The diagnosis of JGCT is made by pathology definitely. The prognosis is poor when patient has high mitotic index. Cytoreductive surgery is the treatment of choice and combination chemotherapy may be helpful to improve the prognosis of JGCT.

Adolescent↗

PubMed2002

[Evaluation of myometrial invasion in endometrial carcinoma].

OBJECTIVE: To determine the value of preoperative ultrasound, intraoperative gross visual inspection and postoperative bulk specimen measurement in evaluating the diagnosis of myometrial invasion in endometrial carcinoma. METHODS: A total of 133 cases of women with endometrial carcinoma were analyzed focusing on evaluating the diagnosis of myometrial invasion by preoperative ultrasound, intraoperative gross visual inspection and postoperative bulk specimen measurement. The relationship between CA(125) and endometrial carcinoma of 91 cases of endometrial carcinoma was also analyzed. RESULTS: In the diagnosis of myometrial invasion and deep myometrial invasion, ultrasound showed a sensitivity of 62.6% and 47.8% and a specificity of 67.7% and 90.0%, respectively, and intraoperative gross visual inspection showed a sensitivity of 59.6% and 73.9% and a specificity of 76.5% and 94.6%, respectively. The sensitivity of postoperative bulk specimen measurement was 70.0% and 94.4% and the specificity was 92.0% and 97.7%, respectively. The levels of CA(125) had no correlation with depth of myometrial invasion in endometrial carcinoma, but they had correlation with International Federation of Gynecology and Obstetrics (FIGO) stage. CONCLUSIONS: Preoperative ultrasound, intraoperative gross visual inspection and postoperative bulk specimen measurement were helpful to the diagnosis of depth of myometrial invasion in endometrial carcinoma, and postoperative bulk specimen measurement seems to be better. CA(125) could not evaluate depth of myometrial invasion in endometrial carcinoma.

Endometrial Neoplasms↗

PubMed2002

[Clinical analyses of 42 cases of urinary tract injury in gynecologic surgery].

OBJECTIVE: To determine the clinical characteristics and management of urinary tract injuries incidental to gynecologic surgery. METHODS: During the study period from Jan. 1, 1990 to Dec. 31, 2001, forty-two patients with urinary tract injuries in gynecologic surgery were analyzed retrospectively focusing on type and time of injury, diagnostic methods and managements of urinary fistula. RESULTS: Forty-two urological injuries were incurred during the performance of 12 849 gynecologic surgical procedures, an incidence of 0.33% including of 11 ureteral injuries and 31 bladder injuries, an incidence of 0.09% and 0.24% respectively. Of the 11 ureteral injuries 5 occurred in the lower ureter, 4 occurred at the level of vecical entrance and 2 were in the region of the infundibulopelvic ligaments. Of the bladder injuries, all 31 occurred at the bottom or back of the bladder. Urinary tract injury was made intraoperatively in 32 patients (76%) and made postoperatively in 10 patients (24%). Urinary fistulae occurred in 14 patients (33%). Ten patients with urinary fistulae were diagnosed by comparing the concentration of electrolyte, urea nitrogen and creatine in drainage fluid with those in urine and blood. Infusion of methylene blue and/or cystoscopy were checked in 9 patients and 4 bladder fistulae were found positive results. All 8 ureteral fistulae were diagnosed by intravenous pyelography. An appropriate repair during operation, putting the double J-catheter and/or catheterization was useful. Forty-one patients were healed. CONCLUSION: Most of urinary tract injuries in gynecologic surgery had optimal results when they were diagnosed early and managed correctly.

Female↗

PubMedDate not supplied

A new platform for oligonucleotide delivery utilizing the PEG prodrug approach.

The oligonucleotide (oligo, ODN), Genasense (GS), an ODN currently waiting for FDA approval, was chosen as a model and modified with a 5' or 3' aminohexyl functionality (1 and 4, respectively) using solid-state synthesis. These amino derivatives were reacted with different releasable PEGs (rPEGs). The in vitro results of the PEG-modified oligos (Table 1) clearly show a substantial increase in rat plasma half-life and enhanced stability against a variety of nucleases, especially the predominant nuclease (PEII) in mammals, which is the main source of oligo degradation in cells. The advantage of using a PEG prodrug approach was further demonstrated by the pharmacokinetic (PK) results, which exhibited much greater C(max), plasma half-life, and area under the curve (AUC) for 3 compared to unmodified GS. A key step in the synthesis of ODN prodrug conjugates with a dye label was also accomplished successfully by employing dihydropyran derivatives of alcohols and acids as orthogonal protecting groups during the synthesis.

Animals↗

PubMedDate not supplied

Structure-function engineering of interferon-beta-1b for improving stability, solubility, potency, immunogenicity, and pharmacokinetic properties by site-selective mono-PEGylation.

Recombinant interferon-beta-1b (IFN-beta-1b) is used clinically in the treatment of multiple sclerosis. In common with many biological ligands, IFN-beta-1b exhibits a relatively short serum half-life, and bioavailability may be further diminished by neutralizing antibodies. While PEGylation is an approach commonly employed to increase the blood residency time of protein therapeutics, there is a further requisite for molecular engineering approaches to also address the stability, solubility, aggregation, immunogenicity and in vivo exposure of therapeutic proteins. We investigated these five parameters of recombinant human IFN-beta-1b in over 20 site-selective mono-PEGylated or multi-PEGylated IFN-beta-1b bioconjugates. Primary amines were modified by single or multiple attachments of poly(ethylene glycol), either site-specifically at the N-terminus, or randomly on the 11 lysines. In two alternate approaches, site-directed mutagenesis was independently employed in the construction of designed IFN-beta-1b variants containing either a single free cysteine or lysine for site-specific PEGylation. Optimization of conjugate preparation with 12 kDa, 20 kDa, 30 kDa, and 40 kDa amine-selective PEG polymers was achieved, and a comparison of the structural and functional properties of the IFN-beta-1b proteins and their PEGylated counterparts was conducted. Peptide mapping and MALDI-TOF mass spectrometric analysis confirmed the attachment sites of the PEG polymer. Independent biochemical and bioactivity analyses, including antiviral and antiproliferation bioassays, circular dichroism, capillary electrophoresis, flow cytometric profiling, reversed phase and size exclusion HPLC, and immunoassays demonstrated that the functional activities of the designed IFN-beta-1b conjugates were maintained, while the formation of soluble or insoluble aggregates of IFN-beta-1b was ameliorated. Immunogenicity and pharmacokinetic studies of selected PEGylated IFN-beta-1b compounds in mice and rats demonstrated both diminished IgG responses, and over 100-fold expanded AUC exposure relative to the unmodified protein. The results demonstrate the capacity of this macromolecular engineering strategy to address both pharmacological and formulation challenges for a highly hydrophobic, aggregation-prone protein. The properties of a lead mono-PEGylated candidate, 40 kDa PEG2-IFN-beta-1b, were further investigated in formulation optimization and biological studies.

Amides↗