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响应面法在壳聚糖/海藻酸钠纳米粒作为重组人骨形态发生蛋白-2传递载体的统计优化中的应用。

Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery.

机构信息

Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Departments of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Int J Nanomedicine. 2020 Oct 29;15:8345-8356. doi: 10.2147/IJN.S250630. eCollection 2020.

Abstract

PURPOSE

In this study, chitosan/alginate nanoparticles are prospected as a carrier for controlled release of recombinant human bone morphogenetic protein-2 (rhBMP-2).

MATERIALS AND METHODS

The rhBMP-2-loaded chitosan/alginate nanoparticles (Cs/Alg/B NPs) were prepared using the ionic gelation (IG) method. The current research was conducted to optimize the effective factors for entrapping rhBMP-2 in Cs/Alg NPs using response surface methodology (RSM) and the Box-Behnken design (BBD). The variables were the Cs/Alg molecular weight (Mw) ratios (1-3), pH (4.8-5.5), stirring rates (900-1300 rpm) and the responses included size, ζ-potential, polydispersity index (PDI), loading efficacy (LE), cumulative release (CR), and morphological degradation time (MDE). Then, the morphological properties of optimum formulation were studied for post-characterization. In the next step, the MTT assay for the optimized run was done for 24 and 48 hours.

RESULTS

The results revealed that the optimum conditions for the mentioned variables were stirring rate=1100 rpm, pH=5.15, and Cs/Alg Mw ratio=1.75 based on numerical optimization. It was shown that the average particle size and loading efficacy at optimum conditions were 253 nm and 67%, respectively. Other responses were as follows: CR=66%, ζ-potential=+35mV, PDI=0.5, and MDT=7 days.

CONCLUSION

The results have suggested that the statistical optimization of rhBMP-2 offers the possibility of preparing Cs/Alg/B NPs with a favorable size, controlled release characteristics, and high loading efficiency. It is expected that the acquired optimum conditions will be useful for efficient rhBMP-2 delivery.

摘要

目的

本研究拟将壳聚糖/海藻酸钠纳米粒作为载体用于控制释放重组人骨形态发生蛋白-2(rhBMP-2)。

材料和方法

采用离子凝胶(IG)法制备载 rhBMP-2 的壳聚糖/海藻酸钠纳米粒(Cs/Alg/B NPs)。本研究采用响应面法(RSM)和 Box-Behnken 设计(BBD)优化了影响 Cs/Alg NPs 包埋 rhBMP-2 的有效因素。变量为壳聚糖/海藻酸钠分子量比(1-3)、pH 值(4.8-5.5)、搅拌速度(900-1300 rpm),响应值包括粒径、ζ-电位、多分散指数(PDI)、载药量(LE)、累积释放率(CR)和形态降解时间(MDE)。然后,对最佳处方的形态学特性进行了进一步的表征。下一步,对优化后的配方进行 24 小时和 48 小时的 MTT 测定。

结果

结果表明,基于数值优化,所述变量的最佳条件为搅拌速度=1100 rpm、pH=5.15、壳聚糖/海藻酸钠分子量比=1.75。结果表明,最佳条件下的平均粒径和载药量分别为 253nm 和 67%。其他响应值分别为:CR=66%、ζ-电位=+35mV、PDI=0.5、MDT=7 天。

结论

研究结果表明,rhBMP-2 的统计学优化为制备具有良好粒径、控释特性和高载药效率的 Cs/Alg/B NPs 提供了可能。预计获得的最佳条件将有助于 rhBMP-2 的高效传递。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5241/7606360/511a9a2bc1f5/IJN-15-8345-g0001.jpg

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