Nanotechnology, Science and Applications Dovepress
Nanotechnology, Science and Applications Dovepress
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DOI：
10.2147/nsa
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发表时间：
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通讯作者：
Mas Jaffri;Masarudin;S. Cutts;Benny J. Evison;Don R. Phillips;P. Pigram;Correspondence Mas;
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作者：
Mas Jaffri;Masarudin;S. Cutts;Benny J. Evison;Don R. Phillips;P. Pigram;Correspondence Mas;
因素确定的稳定性，尺寸分布，和细胞积累的小，单分散性壳聚糖纳米颗粒作为候选载体抗癌药物输送：应用程序的被动封装的[ 14 C]-阿霉素摘要：纳米载体的制造参数的发展是其成功的管理在治疗应用中的关键。在这项研究中，均匀分布的壳聚糖纳米颗粒（CNP）的直径小至62 nm和多分散指数（PDI）为0.15的合成和纯化使用一个简单的，强大的方法，是高度可重复的。用三聚磷酸钠改性壳聚糖聚合物的离子凝胶化制备纳米粒子。使用该方法，通过选择性有效离心从纳米颗粒群中的单个颗粒机械分离较大的聚集体。使用原子力显微镜证实了解聚的单分散纳米颗粒的存在。阴离子、pH值和浓度等因素直接影响纳米粒子的大小和稳定性。最小的纳米颗粒群体在流体动力学尺寸上为1.62 nm，具有0.15的低PDI，表明高颗粒均匀性。CNP是高度稳定的，并在细胞培养条件下在补充血清的培养基中保持其单分散形态长达72小时，然后在6天内缓慢降解。细胞活力测定表明，细胞在暴露于1 mg/mL CNP 72小时后仍保持活力，表明纳米颗粒具有良好的耐受性，非常适合生物医学应用。使用异硫氰酸荧光素标记的CNPs的细胞摄取研究表明，癌细胞在治疗后30分钟容易积聚纳米颗粒，并且纳米颗粒在治疗后24小时内持续存在于细胞内。作为用于抗癌治疗应用的原理证明，将抗癌剂多柔比星的[ 14 C]-放射性标记形式有效包封在CNP中，证实了使用该系统作为药物递送载体的可行性。
Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [ 14 C]-doxorubicin Abstract: Development of parameters for the fabrication of nanosized vectors is pivotal for its successful administration in therapeutic applications. In this study, homogeneously distributed chitosan nanoparticles (CNPs) with diameters as small as 62 nm and a polydispersity index (PDI) of 0.15 were synthesized and purified using a simple, robust method that was highly reproducible. Nanoparticles were synthesized using modified ionic gelation of the chitosan polymer with sodium tripolyphosphate. Using this method, larger aggregates were mechanically isolated from single particles in the nanoparticle population by selective efficient centrifugation. The presence of disaggregated monodisperse nanoparticles was confirmed using atomic force microscopy. Factors such as anions, pH, and concentration were found to affect the size and stability of nano-particles directly. The smallest nanoparticle population was ∼62 nm in hydrodynamic size, with a low PDI of 0.15, indicating high particle homogeneity. CNPs were highly stable and retained their monodisperse morphology in serum-supplemented media in cell culture conditions for up to 72 hours, before slowly degrading over 6 days. Cell viability assays demonstrated that cells remained viable following a 72-hour exposure to 1 mg/mL CNPs, suggesting that the nanopar-ticles are well tolerated and highly suited for biomedical applications. Cellular uptake studies using fluorescein isothiocyanate-labeled CNPs showed that cancer cells readily accumulate the nanoparticles 30 minutes posttreatment and that nanoparticles persisted within cells for up to 24 hours posttreatment. As a proof of principle for use in anticancer therapeutic applications, a [ 14 C]-radiolabeled form of the anticancer agent doxorubicin was efficiently encapsulated within the CNP, confirming the feasibility of using this system as a drug delivery vector.