Liposome-Templated Hydrogel Nanoparticles as Vehicles for Enzyme-Based Therapies

Abstract

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.

Synthesis and formulation of functional bionanomaterials with superoxide dismutase activity

“…42,43 Moreover, hydrogel vehicles were synthesized and SOD was encapsulated inside the nanoparticles to get protected from antibodies and degradation. 44 The immobilization process did not affect the catalytic activity and the developed system was proposed as a promising tool for enzymatic therapy.…”

Immobilization of Superoxide Dismutase on Polyelectrolyte‐Functionalized Titania Nanosheets

“…Besides,apromising way to improve the sensitivity and recyclability of SOD is to immobilize it on solid supports, such as inorganic particles, [19][20][21][22][23] polymers, [24,25] or other hybrid mate-rials. [26] In addition, enzyme cascades containing SOD, catalase, or other peroxidase enzymes have been prepared, for which these natural biocatalysts were confined in silica nanoparticles, [27,28] polymericv esicles, [29][30][31] or nanocontainers [32] to mimic the cellulare nvironmenta nd to achieve complete decomposition of ROS into molecular oxygen and water.A ntioxidant enzymes have also been covalently linked to polymeric chains to obtain such antioxidant cascades.…”

Lipobeads

“…The other example of successful coencapsulation of hydrophilic proteins (IL-2) and small hydrophobic molecules (TGF-receptor-I inhibitor, SB505124) into the biodegradable hydrogel core of lipobeads has been presented in [11]: encapsulation efficiencies were 80 and 36%, respectively, and UV polymerization did not compromise bioactivity of both immunomodulators. Recently, PAAm lipobeads with a good encapsulation efficiency (37%) of enzymes (bovine Cu, Zn-superoxide dismutase, and bovine milk lactoperoxidase) were synthesized to prove that the UV irradiation used for interior gelation did not cause any reduction in the enzymatic activity of the proteins [37].…”

“…As it was mentioned in Section 2.5.1, so far the only test enzymes were loaded into the lipobeads interior to show retention of their enzymatic activity after release from the hydrogel core [37].…”