Poly(L-glutamic acid)-co-poly(ethylene glycol) block copolymers for protein conjugation
| Autor: | Marino Bellini, Katia Maso, Ilaria Marigo, Antonella Grigoletto, Hiroki Yoshioka, Vincenzo Ingangi, Kamiya Masaki, Midori Hirai, Lucia Raccagni, Akira Suzuki, Gianfranco Pasut |
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| Rok vydání: | 2020 |
| Předmět: |
Polymers
Glutamic Acid Pharmaceutical Science 02 engineering and technology G-CSF Polymer conjugation Polyethylene Glycols Rats Sprague-Dawley Mice 03 medical and health sciences chemistry.chemical_compound PEG ratio Copolymer Animals Moiety 030304 developmental biology chemistry.chemical_classification 0303 health sciences Human growth hormone Chemistry Protein delivery PEGylation Glutamic acid Polymer 021001 nanoscience & nanotechnology Combinatorial chemistry Rats Mice Inbred C57BL 0210 nano-technology Ethylene glycol Conjugate |
| Zdroj: | Journal of Controlled Release. 324:228-237 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2020.05.015 |
| Popis: | Poly(L-glutamic acid)-co-poly(ethylene glycol) block copolymers (PLE-PEG) are here investigated as polymers for conjugation to therapeutic proteins such as granulocyte colony stimulating factor (G-CSF) and human growth hormone (hGH). PLE-PEG block copolymers are able to stabilize and protect proteins from degradation and to prolong their residence time in the blood stream, features that are made possible thanks to PEG's intrinsic properties and the simultaneous presence of the biodegradable anionic PLE moiety. When PLE-PEG copolymers are selectively tethered to the N-terminus of G-CSF and hGH, they yield homogeneous monoconjugates that preserve the protein's secondary structure. During the current study the pharmacokinetics of PLE10-PEG20k-G-CSF and PLE20-PEG20k-G-CSF derivatives and their ability to induce granulopoiesis were, respectively, assessed in Sprague-Dawley rats and in C57BL6 mice. Our results show that the bioavailability and bioactivity of the derivatives are comparable to or better than those of PEG20k-Nter-G-CSF (commercially known as Pegfilgrastim). The therapeutic effects of PLE10-PEG20k-hGH and PLE20-PEG20k-hGH derivatives tested in hypophysectomized rats demonstrate that the presence of a negatively charged PLE block enhances the biological properties of the conjugates additionally with respect to PEG20k-Nter-hGH. |
| Databáze: | OpenAIRE |
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