1,721,071 research outputs found
Pathophysiological and histomorphological evaluation of polyacryloylmorpholine vs polyethylene glycol modified superoxide dismutase in a rat model of ischaemia/reperfusion injury
No full textInt J Artif Organs. 1996 Dec;19(12):730-4.
Pathophysiological and histomorphological evaluation of polyacryloylmorpholine vs polyethylene glycol modified superoxide dismutase in a rat model of ischaemia/reperfusion injury.
Rocca M, Giavaresi G, Caliceti P, Veronese FM, Giardino R.
SourceDepartment of Experimental Surgery, Istituto di Ricerca Codivilla-Putti I.O.R. and Surgical Pathophysiology, Medical School, University of Bologna, Italy.
Abstract
Twenty Wistar rats were divided into two groups. Both underwent acute ischaemia followed by reperfusion of the left hind limb. The first group was a control group while the second was treated with PAcM-SOD. The survival percentage of the limb after 10 days was 30% for the first group and 70% for the second. Neither linear regression nor correlation were found between groups as far as the survival percentage of the limb after 10 days and reperfusion pmO2 data were concerned. After ten days the histomorphological analysis was significant regarding the fibre diameter and the percentage of central located nuclei in the specimens of PAcM-SOD treated limbs compared to normal limbs, but not when compared to the muscular fibres of the control group. Comparing these results with others obtained with native SOD and monomethoxypoly(ethylene glycol) modified SOD (mPEG-SOD) used in the same experimental model, we can conclude that the clinical and morphological results were better using mPEG-SOD, and that PAcM-SOD does have a protective effect on ischaemic muscle damage, although it is not as effective as mPEG-SOD in preventing ischaemia/reperfusion injury
Improvement of Drug Therapy by Covalent PEG Conjugation: An Overview From a Research Laboratory
No full textIn the last two decades, efforts focused in the field
of drug delivery have made it possible to reach important
goals, especially with proteins and peptides. The story of
the evolution of this matter is vast and it is difficult to summarize
its various aspects in a single review. On the other
hand, it could be really interesting to look at the inside story
of a typical academic research lab that has dedicated almost
all its resources to drug delivery. In our case, an initial interest
in the issue of protein conformation stability soon paved
the way for a new area of study: the modification of proteins
with synthetic polymers. We have seen this technique transformed
from a crude and inhomogeneous procedure into a
well-recognized and successful approach. This great advance
has been possible thanks to the development of dedicated
chemical coupling methods and to the better understanding
of the behavior of polymers in vivo. In particular,
among the several polymers investigated, PEG has became
the best polymer for protein modification. Exploiting the
unique properties of this polymer, we have conducted several
investigations in the field of protein PEGylation and then
transferred the acquired know-how to the development of
conjugates with low molecular weight drug. This last aspect
still presents several unmet needs that are awaiting proper
solutions
PEGylation: Posttranslational bioengineering of protein biotherapeutics
No full textPolymer conjugation, especially by poly(ethylene glycol),
has become a leading technology for the delivery
of proteins. Nowadays, biotech drugs represent an
increasing share of the new approved drugs, but their
use is often prevented by drawbacks and safety concern.
In particular, short in vivo half-life and immunogenicity
are significant problems faced by the
researchers dealing with the development of protein
and peptide drugs. The chemical linking of a polymer to
the protein surface has proved effective in prolonging
protein blood circulation and reducing the immunogenicity
by decreasing renal clearance and shielding
immunogenic epitopes, respectively. So far, PEGylation
has already led to nine marketed conjugates with
great therapeutic success
Custom-tailored pharmacokinetics and pharmacodynamics via chemical modifications of biotech drugs
No full textPolymer-drug conjugation, recent achievementsand general strategies
No full textThe field of drug delivery is fast expanding and its potentials have already been proved by the many products on the market. Among all approaches, polymer conjugation is a well known and widely exploited technique useful to improve therapeutic properties of peptides, proteins, small molecules or oligonucleotides. Polymer conjugated drugs generally exhibit prolonged half-life, higher stability, water solubility, lower immunogenicity and antigenicity and often also specific targeting to tissues or cells. This technology, exploited for the first time in the fifties and sixties, received a great development both for the introduction and study of new and different polymers and for the progresses in the chemical strategies of coupling. Polymer-drug conjugates are already on the market for the treatment of different diseases, demonstrating the potentials of the technology. Furthermore, new polymers, in addition to the most known N-(2-hydroxypropyl)methacrylamide copolymer (HPMA), polyglutamic acid (PGA) and poly(ethylene glycol) (PEG), are continuously investigated and proposed. The review will discuss the most recent achievements in polymer conjugation with special emphasis on PEG application strategies and approved products
Extensive crosslinking between subunits of oligomeric proteins induced by furocoumarins plus UV-A irradiation.
No full textPegylation for improving the effectiveness of therapeutic biomolecules
No full textProteins have gained an important role in clinical practice, and they are the treatment of choice or even the only therapy for several pathologies. Unfortunately, their great potential is often hampered by relevant shortcomings such as immunogenicity and fast body clearance. Polymer conjugation, especially with polyethylene glycol (PEG), has emerged as a suitable drug delivery solution to address these drawbacks. Furthermore, this technology has been found to be a powerful approach to increase the general therapeutic efficacy of biomolecules. After the first PEG-protein derivatives were released, it was clear that a wider exploitation of PEGylation could be reached only through thorough development of the methods of conjugation. At the moment, different PEG coupling strategies and PEG polymers are available. The research in this field is very active and a large effort has been focused on developing releasable PEGs, which are polymers able to release the conjugated protein. This feature enables the recovery of the protein activity that is commonly reduced after polymer coupling
Second-Generation Pharmaceutical Proteins - EUFEPS Workshop on Optimizing Biotech Medicines
No full textThe European Federation for Pharmaceutical Sciences (EUFEPS) Workshop on Optimizing Biotech Medicines focused on recent research for pharmaceutical proteins, and was attended by approximately 100 participants, mostly from biotech companies. Present and future advancements in the field of therapeutic proteins were discussed, and the meeting included an emphasis on the use of antibodies as drugs. In opening remarks, Dean Crommelin (Top Institute Pharma, the Netherlands) and Ulrike Holzgrabe (University of Würzburg, Germany) focused on the increasing importance and value of biotech drugs, which increased in number by 18% in 2006 to account for approximately 10% of the total drug market. However, such an increase requires an important reconsideration and development of basic factors such as the preparation and use of therapeutic proteins, the capability of protein production by biotech pharma, immunogenicity side effects, new analytical processes, and specially devised formulations
PEGylation, successful approach to drug delivery.
No full textPEGylation defines the modification of a protein, peptide or non-peptide molecule by the linking of one or more poly(ethylene glycol) (PEG) chains. This polymer appeared the best choice being non-toxic, non-immunogenic, non-antigenic, highly soluble in water and FDA approved. The PEG-drug conjugates take advantages from: i) a prolonged residence in body, ii) a decreased degradation by metabolic enzymes, iii) a reduction or elimination of protein immunogenicity.
Thanks to these favorable properties, PEGylation is now playing an important role in drug delivery enhancing thepotentials of peptides and proteins as therapeutic agents
- …
