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首页> 外文期刊>Journal of biomedical nanotechnology >Cellular Internalization Mechanisms of Polyanhydride Particles: Implications for Rational Design of Drug Delivery Vehicles
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Cellular Internalization Mechanisms of Polyanhydride Particles: Implications for Rational Design of Drug Delivery Vehicles

机译：酸酐颗粒的细胞内在化机制：对药物输送载体的合理设计的启示。

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Polyanhydride nanoparticles have emerged as a versatile delivery platform, due to their ability to encapsulate diverse drugs, immunogens, antibodies, and proteins. However, mechanistic studies on the effects of particle chemistry interactions with immune cells have yet to be described. Understanding the mechanism by which these particles are internalized by immune cells will enable rational selection of delivery vehicles for specific applications. In the present study, the internalization, mechanism(s) of uptake by monocytes, and intracellular fate of polyanhydride nanoparticles were evaluated using copolymers based on 1,6- bis(p-carboxyphenoxy) hexane (CPH), sebacic acid (SA), and 1,8-bis(p-carboxyphenoxy)3,6- dioxaoctane (CPTEG). The results showed that 20: 80 CPH: SA and 20: 80 CPTEG: CPH nanoparticles were internalized to a greater extent by monocytes as compared to the 50: 50 CPH: SA and 50: 50 CPTEH: CPH nanoparticles. Further, cytochalasin-D treatment of cells inhibited uptake of all the particles, regardless of chemistry, indicating that actin-mediated uptake is the primary mechanism of cellular entry for these particles. The insights gained from these studies were used to identify lead nanoparticle formulations to enhance treatment of intracellular bacterial infections. The use of doxycycline-loaded nanoparticles exhibited enhanced therapeutic efficacy compared to soluble drug in treating monocyte monolayers infected with the virulent intracellular pathogen Brucella abortus. Altogether, these studies demonstrate how rational design and selection of nanoscale delivery platforms can be used for a wide spectrum of biomedical applications.
机译：聚酸酐纳米粒子因其封装各种药物，免疫原，抗体和蛋白质的能力而成为一种通用的递送平台。但是，有关与免疫细胞发生粒子化学相互作用的机理的研究尚未描述。了解这些颗粒被免疫细胞内在化的机制将使得能够针对特定应用合理选择递送载体。在本研究中，使用基于1,6-双（对-羧基苯氧基）己烷（CPH），癸二酸（SA）的共聚物评估了聚酸酐纳米颗粒的内在化，单核细胞摄取的机制和细胞内命运。和1,8-双（对羧基苯氧基）3,6-二氧八辛烷（CPTEG）。结果显示，与50:50 CPH：SA和50:50 CPTEH：CPH纳米粒子相比，单核细胞更容易内化20:80 CPH：SA和20:80 CPTEG：CPH纳米粒子。另外，细胞的细胞松弛素-D处理抑制所有颗粒的摄取，而与化学无关，这表明肌动蛋白介导的摄取是这些颗粒进入细胞的主要机制。从这些研究中获得的见识用于鉴定铅纳米颗粒制剂以增强对细胞内细菌感染的治疗。与可溶性药物相比，使用多西环素加载的纳米颗粒在治疗感染有毒性细胞内病原体布鲁氏菌流产的单核细胞单层细胞中显示出增强的治疗功效。总而言之，这些研究证明了纳米级递送平台的合理设计和选择可如何用于广泛的生物医学应用。

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