| Autor: |
Javan Nikkhah S; Department of Physics, Bernal Institute, University of Limerick, V94 T9PX Limerick, Republic of Ireland.; Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick V94 T9PX, Republic of Ireland., Thompson D; Department of Physics, Bernal Institute, University of Limerick, V94 T9PX Limerick, Republic of Ireland. |
| Jazyk: |
angličtina |
| Zdroj: |
Biomacromolecules [Biomacromolecules] 2022 Sep 12; Vol. 23 (9), pp. 3875-3886. Date of Electronic Publication: 2022 Aug 02. |
| DOI: |
10.1021/acs.biomac.2c00699 |
| Abstrakt: |
Antibody therapy generally requires parenteral injection to attain the required bioavailability and pharmacokinetics, but improved formulations may slow enzymatic degradation of the antibody in the gastrointestinal tract, permitting the use of noninvasive oral delivery. Rationally designed carrier materials can potentially improve therapeutic activity both by shielding fragile biopharmaceuticals from proteolytic degradation and targeting specific receptors in vivo. One potentially useful class of protein carriers is block copolyelectrolytes, one polyelectrolyte plus one neutral hydrophilic polymer block, that self-assemble into stable micelles, providing a simple and biocompatible nanocapsule separating the protein from the outer medium. Here, we develop and implement an integrated mesoscale model to design molecular structures for block copolyelectrolyte nanocapsules predicted to protect Trastuzumab, an antibody used to treat breast cancer, in the low pH gastrointestinal tract and to selectively release this antibody in the more neutral intestinal environment. The simulations show a tightly packed self-assembled core-shell structure at pH = 3 that is ruptured and dynamically reassembled into a weaker structure at pH = 7. Our model identifies that the designed block copolyelectrolyte characteristics, such as block length ratio, can control the level of drug protection and release in vivo, providing simple design rules for engineering polyelectrolyte-based formulations that may allow oral administration of targeted antibody chemotherapies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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