Chitosan-modified lipid nanovesicles for efficient systemic delivery of l-asparaginase

• Chitosan-lipid nanovesicles were applied to deliver therapeutic enzymes.
• ACLNs markedly increased the enzymatic activity and improved stabilities.
• ACLNs favorably changed the in vivo kinetic characteristics.
• ACLNs exhibited higher anti-lung-cancer activity than free ASP.
• The possible mechanisms for the enhanced properties of ASP were preliminary explored.

The goal of this study was to evaluate the enhanced catalytic activity, increased stability, in vitro anti-cancer effects on H446 cells and in vivo bioavailability of novel enzyme delivery nanovesicles (l-asparaginase containing chitosan modified lipid nanovesicles, ACLNs) when administered intravenously. It was the first time for the chitosan-modified lipid nanovesicles to be fabricated to deliver l-asparaginase (ASP, a therapeutic enzyme) efficiently. It was indicated that ACLNs markedly increased the enzymatic activity, improved the temperature/acid-base/proteolytic stabilities and favorably changed the in vivo kinetic characteristics. Moreover, ACLNs exhibited higher anti-lung-cancer activity than free ASP. The possible existence status of ASP in ACLNs and the fluorescence changes of ACLNs reflecting the conformational changes after heat treatment were preliminary explored. ACLNs might be novel promising nanovesicles for effective systemic delivery of therapeutic enzyme ASP.

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