Enhanced stability of complex coacervate core micelles following different core-crosslinking strategies

Kembaren, Riahna; Kleijn, J. Mieke; Borst, Jan Willem; Kamperman, Marleen; Hofman, Anton H.

doi:10.1039/d2sm00088a

Cited by 4 publications

(12 citation statements)

References 72 publications

(140 reference statements)

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“…Such a high sensitivity to salt has been reported before for C3M systems . There are many ways to increase the stability of C3Ms, namely, by careful tuning of the corona/core length ratio, increasing the hydrophobicity of the polyelectrolyte blocks, increasing either or both polyelectrolyte block lengths, or by cross-linking the coacervate core. ,,− However, we decided to take advantage of this sensitivity feature in order to endow the hybrid coating with a salt-triggered reversibility property.…”

Section: Resultsmentioning

confidence: 99%

Scalable Fabrication of Reversible Antifouling Block Copolymer Coatings via Adsorption Strategies

Maan

Graafsma

Hofman

et al. 2023

ACS Appl. Mater. Interfaces

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Fouling remains a widespread challenge as its nonspecific and uncontrollable character limits the performance of materials and devices in numerous applications. Although many promising antifouling coatings have been developed to reduce or even prevent this undesirable adhesion process, most of them suffer from serious limitations, specifically in scalability. Whereas scalability can be particularly problematic for covalently bound antifouling polymer coatings, replacement by physisorbed systems remains complicated as it often results in less effective, low-density films. In this work, we introduce a two-step adsorption strategy to fabricate high-density block copolymer-based antifouling coatings on hydrophobic surfaces, which exhibit superior properties compared to one-step adsorbed coatings. The obtained hybrid coating manages to effectively suppress the attachment of both lysozyme and bovine serum albumin, which can be explained by its dense and homogeneous surface structure as well as the desired polymer conformation. In addition, the intrinsic reversibility of the adhered complex coacervate core micelles allows for the successful triggered release and regeneration of the hybrid coating, resulting in full recovery of its antifouling properties. The simplicity and reversibility make this a unique and promising antifouling strategy for large-scale underwater applications.

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Section: Resultsmentioning

confidence: 99%

Scalable Fabrication of Reversible Antifouling Block Copolymer Coatings via Adsorption Strategies

Maan

Graafsma

Hofman

et al. 2023

ACS Appl. Mater. Interfaces

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“…17 Another challenge is the tendency of coacervates to fuse over time during storage, which could potentially be addressed by utilizing stabilizing agents, chemical cross-linking, or incorporating liposome or polymersome delivery systems. 71,79 Additionally, advanced imaging could enable real-time tracking to help elucidate the mechanisms of uptake. 33 The successful delivery of therapeutic mRNA via coacervates could have significant implications for the treatment of various diseases.…”

Section: ■ Conclusionmentioning

confidence: 99%

“…Moreover, in addition to the length and frequency of RNA molecules (with longer RNA molecules being more conducive to coacervation), chemical cross-linking of coacervate components can provide a more stable network to improve encapsulation efficiency. This can be achieved through various methods such as chemical and enzymatic reactions or photopolymerization via irradiation . However, while cross-linking can be beneficial in increasing coacervate stability, it can also limit therapeutic RNA delivery if cross-linking is irreversible.…”

Section: Coacervate-mediated Delivery Of Mrna: Formulation and Optimi...mentioning

confidence: 99%

“…To minimize potential side effects, researchers should explore the use of biocompatible and non-immunogenic materials such as natural polysaccharides (e.g., chitosan or alginate) or coacervate functionalized nanoparticles with modifications to their physiochemical properties (e.g., PEG surface modification, hybrid structures) . Another challenge is the tendency of coacervates to fuse over time during storage, which could potentially be addressed by utilizing stabilizing agents, chemical cross-linking, or incorporating liposome or polymersome delivery systems. , Additionally, advanced imaging could enable real-time tracking to help elucidate the mechanisms of uptake …”

Section: Future Perspectivementioning

confidence: 99%

“…This can be achieved through various methods such as chemical and enzymatic reactions or photopolymerization via irradiation. 79 However, while crosslinking can be beneficial in increasing coacervate stability, it can also limit therapeutic RNA delivery if cross-linking is irreversible. To overcome this challenge, reversible crosslinking strategies such as reactions with dithiobis(succinimidyl propionate) (DTBP), which form disulfide bonds between amine groups of different molecules, can improve stability above salt addition and pH changes.…”

Section: Formulation and Optimization Strategiesmentioning

confidence: 99%

See 2 more Smart Citations

Complex Coacervates as a Promising Vehicle for mRNA Delivery: A Comprehensive Review of Recent Advances and Challenges

Forenzo,

Larsen

2023

Mol. Pharmaceutics

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Messenger RNA (mRNA)-based therapies have gained significant attention, following the successful deployment of mRNA-based COVID-19 vaccines. Compared with traditional methods of genetic modification, mRNA-based therapies offer several advantages, including a lower risk of genetic mutations, temporary and controlled therapeutic gene expression, and a shorter production time, which facilitates rapid responses to emerging health challenges. Moreover, mRNA-based therapies have shown immense potential in treating a wide range of diseases including cancers, immune diseases, and neurological disorders. However, the current limitations of non-viral vectors for efficient and safe delivery of mRNA therapies, such as low encapsulation efficiency, potential toxicity, and limited stability, necessitate the exploration of novel strategies to overcome these challenges and fully realize the potential of mRNA-based therapeutics. Coacervate-based delivery systems have recently emerged as promising strategies for enhancing mRNA delivery. Coacervates, which are formed by the aggregation of two or more macromolecules, have shown great potential in delivering a wide range of therapeutics due to their ability to form a separated macromolecular-rich fluid phase in an aqueous environment. This phase separation enables the entrapment and protection of therapeutic agents from degradation as well as efficient cellular uptake and controlled release. Additionally, the natural affinity of coacervates for mRNA molecules presents an excellent opportunity for enhancing mRNA delivery to targeted cells and tissues, making coacervate-based delivery systems an attractive option for mRNA-based therapies. This review highlights the limitations of current strategies for mRNA delivery and the advantages of coacervate-based delivery systems to enable mRNA therapeutics. Coacervates protect mRNA from enzymatic degradation and enhance cellular uptake, leading to sustained and controlled gene expression. Despite their promising properties, the specific use of coacervates as mRNA delivery vehicles remains underexplored. This review aims to provide a comprehensive overview of coacervate-mediated delivery of mRNA, exploring the properties and applications of different coacervating agents as well as the challenges and optimization strategies involved in mRNA encapsulation, release, stability, and translation via coacervate-mediated delivery. Through a comprehensive analysis of recent advancements and recommended future directions, our review sheds light on the promising role of coacervate-mediated delivery for RNA therapeutics, highlighting its potential to enable groundbreaking applications in drug delivery and gene therapy.

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Reduction-sensitive shell crosslinked TPGS micelles: Formulation and colloidal characterizations

Sarolia,

Shah,

Aswal

et al. 2023

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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Enhanced stability of complex coacervate core micelles following different core-crosslinking strategies

Abstract: The stability of complex coacervate core micelles (C3Ms) against salt and pH changes is improved by chemical crosslinking of the micelle core. Depending on the crosslinking agent, the resulting covalent network is reversible or irreversible.

Cited by 4 publications

References 72 publications

Scalable Fabrication of Reversible Antifouling Block Copolymer Coatings via Adsorption Strategies

Scalable Fabrication of Reversible Antifouling Block Copolymer Coatings via Adsorption Strategies

Complex Coacervates as a Promising Vehicle for mRNA Delivery: A Comprehensive Review of Recent Advances and Challenges

Reduction-sensitive shell crosslinked TPGS micelles: Formulation and colloidal characterizations

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