Novel enzyme formulations for improved pharmacokinetic properties and anti-inflammatory efficacies

Yang, Lan; Yan, Sheng-Lei; Zhang, Yonghong; Hu, Xueyuan; Guo, Qi; Yuan, Yuming; Zhang, Jingqing

doi:10.1016/j.ijpharm.2017.12.030

Cited by 9 publications

(1 citation statement)

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“…Therefore, we speculate that hydrophobic interaction was more likely to be involved in the interaction between BSA and Aase. The binding of enzyme molecules to serum albumin served as a depot of enzymes, altered the in vivo blood circulation time and clearance rate, and finally resulted in improved bioavailability. , In our research, a prolonged circulation time of Aase was observed after encapsulation, along with a lower clearance rate. This alteration was speculated to result from the different interaction behaviors between Aase/AS@BNV and serum proteins.…”

Section: Resultsmentioning

confidence: 51%

Biomimetic Membrane-Structured Nanovesicles Carrying a Supramolecular Enzyme to Cure Lung Cancer

Huang

Zhou

et al. 2020

ACS Appl. Mater. Interfaces

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Platforms for enzyme delivery must simultaneously have plasma stability, high catalytic activity, and low/no immunogenicity of the enzyme. Here, we designed a novel biomimetic membrane-structured nanovesicle (BNV) to efficiently carry supramolecular enzymes to meet the above requirements. We complexed l-asparaginase (Aase) with hydroxypropyl-β-cyclodextrin (HPCD) to form a supramolecular amphiphile (AS) by self-assembly via noncovalent reversible interactions. We then used the first synthesized polyethylene glycol (PEG 2 kDa)-decorated hyaluronan (12 kDa) and HPCD to self-assemble a semipermeable biomimetic membrane-structured nanovesicle (BNV) together with AS loading. As compared to native Aase, AS@BNV exhibited superior catalytic activity preservation, improved catalytic activity, better pharmacokinetics in rats, enhanced cytotoxic effects, increased antitumor efficacy, and decreased side effects. The underlying mechanisms, such as the autophagy inhibition action against tumor cells, protein–protein docking of the interaction between Aase–serum albumin, and decreased hepatic enzymatic activity, were investigated. This approach paves the way for new types of powerful biomimetic-, supramolecular-, and nanocarrier-based enzymatic therapies.

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Section: Resultsmentioning

confidence: 51%