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基于壳聚糖的细菌灵菌红素微纳米颗粒递送系统:动物模型系统中的优化与毒性

Chitosan based micro and nano-particulate delivery systems for bacterial prodigiosin: Optimization and toxicity in animal model system.

作者信息

Majumdar Subhasree, Mandal Tamal, Mandal Dalia Dasgupta

机构信息

Department of Biotechnology, National Institute of Technology, Mahatma Gandhi Avenue, Durgapur 713209, West Bengal, India; Department of Zoology, Sonamukhi College, Sonamukhi, Bankura 722207, West Bengal, India.

Department of Chemical Engineering, National Institute of Technology, Mahatma Gandhi Avenue, Durgapur 713209, West Bengal, India.

出版信息

Int J Biol Macromol. 2022 Dec 1;222(Pt B):2966-2976. doi: 10.1016/j.ijbiomac.2022.10.072. Epub 2022 Oct 12.

Abstract

Prodigiosin, a red bacterial pigment is a compound with promising therapeutic properties. Major hindrance in applying prodigiosin in pharmaceutics is the insolubility in water and lack of bioavailability. This study aims to optimize two different types of chitosan based delivery systems, microspheres and nanoparticles for prodigiosin derived from Serratia marcescens NITDPER1 through Taguchi method and determine toxicity perspectives. The results revealed 0.5 % chitosan, 1 % sodium-alginate and 5 % CaCl optimum for microsphere and 0.1 % chitosan, 1.5 % TPP and 1.5 % acetic acid for nanoparticle with the entrapment efficiency and maximum release of 89.27 ± 1.2 % and 87.42 ± 1.9 % for microspheres and 96.36 ± 1.7 % and 91.58 ± 2.1 % for nanoparticles. Particle size was 93.03 ± 0.3 μm and 75.1 ± 1.4 nm for micro and nanoformulations. Kinetic parameters of release fitted best with Korsmeyer-Peppas model. Swelling index of microsphere and nanoparticles in pH 6.8 was 799 ± 7.1 % and 35.3 ± 2.1 % respectively. FESEM, FT-IR and XRD revealed spherical morphology, preservation of prodigiosin functional groups and amorphous nature of the formulations. Anticancer IC values were (μg mL) 11.7 ± 1.2, 10.8 ± 1.4 and 9.4 ± 0.8 for free prodigiosin, microsphere and nanoparticles respectively. Toxicity studies on HEK-293 cell line, Daphnia magna and zebrafish model determined non-toxic nature of the bacterial prodigiosin and its formulations revealing suitability of animal system application.

摘要

灵菌红素是一种红色细菌色素,是一种具有潜在治疗特性的化合物。灵菌红素在制药应用中的主要障碍是其在水中的不溶性和生物利用度低。本研究旨在通过田口方法优化两种不同类型的基于壳聚糖的递送系统,即用于源自粘质沙雷氏菌NITDPER1的灵菌红素的微球和纳米颗粒,并确定其毒性情况。结果显示,微球的最佳配方为0.5%壳聚糖、1%海藻酸钠和5%氯化钙,纳米颗粒的最佳配方为0.1%壳聚糖、1.5%三聚磷酸钠和1.5%乙酸,微球的包封率和最大释放率分别为89.27±1.2%和87.42±1.9%,纳米颗粒的包封率和最大释放率分别为96.36±1.7%和91.58±2.1%。微球和纳米制剂的粒径分别为93.03±0.3μm和75.1±1.4nm。释放动力学参数最符合Korsmeyer-Peppas模型。微球和纳米颗粒在pH 6.8时的溶胀指数分别为799±7.1%和35.3±2.1%。场发射扫描电子显微镜(FESEM)、傅里叶变换红外光谱(FT-IR)和X射线衍射(XRD)显示了制剂的球形形态、灵菌红素官能团的保留以及无定形性质。游离灵菌红素、微球和纳米颗粒的抗癌半数抑制浓度(IC值,μg/mL)分别为11.7±1.2、10.8±1.4和9.4±0.8。对人胚肾293细胞系、大型溞和斑马鱼模型的毒性研究确定了细菌灵菌红素及其制剂的无毒性质,表明其适用于动物系统应用。

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