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Interleukin-10 (IL-10) is a key anti-inflammatory and immunosuppressive cytokine and therefore represents a potential therapeutic agent especially in inflammatory diseases. However, despite its proven therapeutic efficacy, its short half-life and proteolytic degradation in vivo combined with its low storage stability have limited its therapeutic use. Strategies have been developed to overcome most of these shortcomings, including in particular bioconjugation with stabilizing agents such as polyethylene glycol (PEG) and poly (vinylpyrolidone) (PVP), but so far these have had limited success. In this paper, we present an alternative method consisting of bioconjugating IL-10 to PVP-coated silver nanoparticles (Ag-PVPs) in order to achieve its storage stability by preventing denaturation and to improve its anti-inflammatory efficacy. Silver nanoparticles capped with a carboxylated PVP were produced and further covalently conjugated with IL-10 protein by carbodiimide crosslinker chemistry. The IL-10 conjugated Ag-PVPs exhibited increased stability and anti-inflammatory effectiveness in vitro. This study therefore provides a novel approach to bioconjugating PVP-coated silver nanoparticles with therapeutic proteins, which could be useful in drug delivery and anti-inflammatory therapies.
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This content will become publicly available on January 1, 2026
Elucidating the role of carrier proteins in cytokine stabilization within double emulsion‐based polymeric nanoparticles
Abstract Polymeric micro‐ and nanoparticles are useful vehicles for delivering cytokines to diseased tissues such as solid tumors. Double emulsion solvent evaporation is one of the most common techniques to formulate cytokines into vehicles made from hydrophobic polymers; however, the liquid–liquid interfaces formed during emulsification can greatly affect the stability and therapeutic performance of encapsulated cytokines. To develop more effective cytokine‐delivery systems, a clear molecular understanding of the interactions between relevant proteins and solvents used in the preparation of such particles is needed. We utilized an integrated computational and experimental approach for studying the governing mechanisms by which interleukin‐12 (IL‐12), a clinically relevant cytokine, is protected from denaturation by albumin, a common stabilizing protein, at an organic‐aqueous solvent interface formed during double emulsification. We investigated protein–protein interactions between human (h)IL‐12 and albumin and simulated these components in pure water, dichloromethane (DCM), and along a water/DCM interface to replicate the solvent regimes formed during double emulsification. We observed that (i) hIL‐12 experiences increased structural deviations near the water/DCM interface, and (ii) hIL‐12 structural deviations are reduced in the presence of albumin. Experimentally, we found that hIL‐12 bioactivity is retained when released from particles in which albumin is added to the aqueous phase in molar excess to hIL‐12 and sufficient time is allowed for albumin‐hIL‐12 binding. Findings from this work have implications in establishing design principles to enhance the stability of cytokines and other unstable proteins in particles formed by double emulsification for improved stability and therapeutic efficacy.
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- Award ID(s):
- 2022138
- PAR ID:
- 10630679
- Publisher / Repository:
- Pubmed
- Date Published:
- Journal Name:
- Bioengineering & Translational Medicine
- Volume:
- 10
- Issue:
- 1
- ISSN:
- 2380-6761
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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