| Autor: |
Liechty WB; McKetta Dept. of Chemical Engineering The University of Texas at Austin Austin TX 78712., Scheuerle RL; McKetta Dept. of Chemical Engineering The University of Texas at Austin Austin TX 78712., Vela Ramirez JE; McKetta Dept. of Chemical Engineering The University of Texas at Austin Austin TX 78712.; Dept. of Biomedical Engineering The University of Texas at Austin Austin TX 78712.; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine The University of Texas at Austin Austin TX 78712., Peppas NA; McKetta Dept. of Chemical Engineering The University of Texas at Austin Austin TX 78712.; Dept. of Biomedical Engineering The University of Texas at Austin Austin TX 78712.; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine The University of Texas at Austin Austin TX 78712.; Depts. of Surgery and Perioperative Care Dell Medical School, The University of Texas at Austin Austin TX 78712.; Division of Molecular Pharmaceutics and Drug Delivery College of Pharmacy, The University of Texas at Austin Austin TX 78712. |
| Jazyk: |
angličtina |
| Zdroj: |
Bioengineering & translational medicine [Bioeng Transl Med] 2018 Nov 22; Vol. 4 (1), pp. 17-29. Date of Electronic Publication: 2018 Nov 22 (Print Publication: 2019). |
| DOI: |
10.1002/btm2.10120 |
| Abstrakt: |
The design of intracellular drug delivery vehicles demands an in-depth understanding of their internalization and function upon entering the cell to tailor the physicochemical characteristics of these platforms and achieve efficacious treatments. Polymeric cationic systems have been broadly accepted to be membrane disruptive thus being beneficial for drug delivery inside the cell. However, if excessive destabilization takes place, it can lead to adverse effects. One of the strategies used to modulate the cationic charge is the incorporation of hydrophobic moieties, thus increasing the hydrophobic content. We have demonstrated the successful synthesis of nanogels based on diethylaminoethyl methacrylate and poly(ethylene glycol) methyl ether methacrylate. Addition of the hydrophobic monomers tert -butyl methacrylate or 2-( tert -butylamino)ethyl methacrylate shows improved polymer hydrophobicity and modulation of the critical swelling pH. Here, we evaluate the cytocompatibility, uptake, and function of these membrane-destabilizing cationic methacrylated nanogels using in vitro models. The obtained results suggest that the incorporation of hydrophobic monomers decreases the cytotoxicity of the nanogels to epithelial colorectal adenocarcinoma cells. Furthermore, analysis of the internalization pathways of these vehicles using inhibitors and imaging flow cytometry showed a significant decrease in uptake when macropinocytosis/phagocytosis inhibitors were present. The membrane-disruptive abilities of the cationic polymeric nanogels were confirmed using three different models. They demonstrated to cause hemolysis in sheep erythrocytes, lactate dehydrogenase leakage from a model cell line, and disrupt giant unilamellar vesicles. These findings provide new insights of the potential of polymeric nanoformulations for intracellular delivery. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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