Importance of Encapsulation Stability of Nanocarriers with High Drug Loading Capacity for Increasing in Vivo Therapeutic Efficacy
| Autor: | Soo Ah Park, Kibeom Kim, Chaekyu Kim, Jun Yong Oh, L. Palanikumar, Eun Seong Choi, Huyeon Choi, Ja-Hyoung Ryu |
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| Rok vydání: | 2018 |
| Předmět: |
Drug
Polymers and Plastics media_common.quotation_subject Mice Nude Antineoplastic Agents Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences Micelle Nanocapsules Biomaterials Mice In vivo Materials Chemistry Animals Humans Colloids Micelles media_common Chemistry Mesoporous silica Silicon Dioxide 021001 nanoscience & nanotechnology 0104 chemical sciences Cross-Linking Reagents Membrane Doxorubicin Drug delivery Biophysics Female Nanocarriers 0210 nano-technology HeLa Cells |
| Zdroj: | Biomacromolecules. 19:3030-3039 |
| ISSN: | 1526-4602 1525-7797 |
| Popis: | Current drug delivery systems are hampered by poor delivery to tumors, in part reflecting poor encapsulation stability of nanocarriers. Although nanocarriers such as polymeric micelles have high colloidal stability and do not aggregate or precipitate in bulk solution, nanocarriers with low encapsulation stability can lose their cargo during circulation in blood due to interactions with blood cells, cellular membranes, serum proteins, and other biomacromolecules. The resulting premature drug release from carriers limits the therapeutic efficacy at target sites. Herein, we report a simple and robust technique to improve encapsulation stability of drug delivery systems. Specifically, we show that installation of disulfide cross-linked noncovalent polymer gatekeepers onto mesoporous silica nanoparticles with a high loading capacity for hydrophobic drugs enhances in vivo therapeutic efficacy by preventing premature release of cargo. Subsequent release of drug cargos was triggered by cleavage of disulfide cross-linking by glutathione, leading to improved antitumor activity of doxoroubicin in mice. These findings provide novel insights into the development of nanocarriers with high encapsulation stability and improved in vivo therapeutic efficacy. |
| Databáze: | OpenAIRE |
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