High Loading Efficiency and Controlled Release of Bioactive Immunotherapeutic Proteins Using Vaterite Nanoparticles,Particle & Particle Systems Characterization

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High Loading Efficiency and Controlled Release of Bioactive Immunotherapeutic Proteins Using Vaterite Nanoparticles
Particle & Particle Systems Characterization ( IF 2.7 ) Pub Date : 2021-06-12 , DOI: 10.1002/ppsc.202100012
Ghizlane Choukrani _{1,

2} , Jimena Álvarez Freile _{1,

2} , Natasha Ustyanovska Avtenyuk _{1,

2} , Wei Wan ₁ , Kerstin Zimmermann ₁ , Edwin Bremer ₂ , Lars Dähne ₁

Affiliation

Nanoparticles may limit off-tumor/on-target ubiquitous activation of signaling by protein-based drugs. However, many challenges still exist in the design of a nanoparticle for protein delivery. In this study, conditions to establish vaterite nanoparticles as a pH-sensitive drug delivery system (DDS) for encapsulated protein drugs are comprehensively evaluated. Low coprecipitation pH of vaterite and protein prevents protein denaturation and yields high loading efficiency. Unprotected vaterite recrystallizes in aqueous solutions within 3 h to calcite and releases the loaded protein completely, but surface-modified particles with carboxyl groups containing polymers prove stable for more than 5 months. Notably, modification of vaterite with sulfonated polymers increases the loading of cationic proteins by a multiple. A system is developed for vaterite exposure to (pH) conditions under body-like-flow rates, with the dissolution of vaterite and simultaneous release of active proteins at tumor microenvironmental pH reaching up to 80% and only 20% at physiological pH within 2 h. Importantly, the immunomodulatory protein tumor necrosis factor preserves its native structure and fully retains functional activity in vitro after release from the particles. In conclusion, the studies described here provide a framework for the development of vaterite-based DDS as a carrier for bioactive protein-based therapeutics.

中文翻译：

使用球霰石纳米颗粒的高负载效率和生物活性免疫治疗蛋白的控制释放

纳米颗粒可能会限制基于蛋白质的药物在肿瘤外/靶上无处不在的信号激活。然而，用于蛋白质递送的纳米颗粒的设计仍然存在许多挑战。在这项研究中，综合评估了将球霰石纳米颗粒作为包封蛋白药物的 pH 敏感药物递送系统 (DDS) 的条件。球霰石和蛋白质的低共沉淀 pH 值可防止蛋白质变性并产生高负载效率。未受保护的球霰石在 3 小时内在水溶液中重结晶成方解石并完全释放负载的蛋白质，但具有含羧基聚合物的表面改性颗粒证明可以稳定超过 5 个月。值得注意的是，用磺化聚合物修饰球霰石会成倍增加阳离子蛋白质的负载。开发了一种用于球霰石在类似身体的流速下暴露于 (pH) 条件的系统，在肿瘤微环境 pH 值下，球霰石溶解并同时释放活性蛋白质，在 2 小时内达到高达 80%，而在生理 pH 值下仅 20% . 重要的是，免疫调节蛋白肿瘤坏死因子保留其天然结构，并在从颗粒释放后在体外完全保留功能活性。总之，这里描述的研究为开发基于球霰石的 DDS 作为基于生物活性蛋白的疗法的载体提供了框架。免疫调节蛋白肿瘤坏死因子保留其天然结构，并在从颗粒释放后在体外完全保留功能活性。总之，这里描述的研究为开发基于球霰石的 DDS 作为基于生物活性蛋白的疗法的载体提供了框架。免疫调节蛋白肿瘤坏死因子保留其天然结构，并在从颗粒释放后在体外完全保留功能活性。总之，这里描述的研究为开发基于球霰石的 DDS 作为基于生物活性蛋白的疗法的载体提供了框架。

更新日期：2021-07-19

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