Liposome-Templated Hydrogel Nanoparticles as Vehicles for Enzyme-Based Therapies
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- 作者：Sara Bobone ; Ermanno Miele ; Barbara Cerroni ; Daniela Roversi ; Alessio Bocedi ; Eleonora Nicolai ; Almerinda Di Venere ; Ernesto Placidi ; Giorgio Ricci ; Nicola Rosato ; Lorenzo Stella
- 刊名：Langmuir
- 出版年：2015
- 出版时间：July 14, 2015
- 年：2015
- 卷：31
- 期：27
- 页码：7572-7580
- 全文大小：459K
- ISSN：1520-5827
文摘
Several diseases are related to the lack or to the defective activity of a particular enzyme; therefore, these proteins potentially represent a very interesting class of therapeutics. However, their application is hampered by their rapid degradation and immunogenic side effects. Most attempts to increase the bioavailability of therapeutic enzymes are based on formulations in which the protein is entrapped within a scaffold structure but needs to be released to exert its activity. In this work, an alternative method will be described, designed to keep the enzyme in its active form inside a nanoparticle (NP) without the need to release it, thus maintaining the protective action of the nanoscaffold during the entire period of administration. In this approach, liposomes were used as nanotemplates for the synthesis of polyacrylamide hydrogel NPs under nondenaturing conditions, optimizing the polymer properties to obtain a mesh size small enough to limit the enzyme release while allowing the free diffusion of its substrates and products. The enzyme Cu, Zn-superoxide dismutase was chosen as a test case for this study, but our results indicate that the approach is generalizable to other enzymes. Biocompatible, size-tunable nanoparticles have been obtained, with a good encapsulation efficiency (37%), in which the enzyme maintains its activity. This system represents a promising tool for enzyme-based therapy, which would protect the protein from antibodies and degradation while allowing it to exert its catalytic activity.