Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Science, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa.
Division of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa.
Int J Mol Sci. 2021 Mar 25;22(7):3359. doi: 10.3390/ijms22073359.
The demand for biodegradable sustained release carriers with minimally invasive and less frequent administration properties for therapeutic proteins and peptides has increased over the years. The purpose of achieving sustained minimally invasive and site-specific delivery of macromolecules led to the investigation of a photo-responsive delivery system. This research explored a biodegradable prolamin, zein, modified with an azo dye (DHAB) to synthesize photo-responsive azoprolamin (AZP) nanospheres loaded with Immunoglobulin G (IgG). AZP nanospheres were incorporated in a hyaluronic acid (HA) hydrogel to develop a novel injectable photo-responsive nanosystem (HA-NSP) as a potential approach for the treatment of chorio-retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. AZP nanospheres were prepared via coacervation technique, dispersed in HA hydrogel and characterised via infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Size and morphology were studied via scanning electron microscopy (SEM) and dynamic light scattering (DLS), UV spectroscopy for photo-responsiveness. Rheological properties and injectability were investigated, as well as cytotoxicity effect on HRPE cell lines. Particle size obtained was <200 nm and photo-responsiveness to UV = 365 nm by decreasing particle diameter to 94 nm was confirmed by DLS. Encapsulation efficiency of the optimised nanospheres was 85% and IgG was released over 32 days up to 60%. Injectability of HA-NSP was confirmed with maximum force 10 N required and shear-thinning behaviour observed in rheology studies. In vitro cell cytotoxicity effect of both NSPs and HA-NSP showed non-cytotoxicity with relative cell viability of ≥80%. A biocompatible, biodegradable injectable photo-responsive nanosystem for sustained release of macromolecular IgG was successfully developed.
多年来，人们对具有微创和较少频繁给药特性的可生物降解缓释载体的需求不断增加，以治疗蛋白质和肽类药物。为了实现大分子的微创和靶向递释，人们开始研究光响应递药系统。本研究探索了一种可生物降解的脯氨酸，即玉米醇溶蛋白，用偶氮染料（DHAB）进行修饰，合成光响应玉米醇溶蛋白纳米球（AZP），并负载免疫球蛋白 G（IgG）。AZP 纳米球被包裹在透明质酸（HA）水凝胶中，开发出一种新型可注射光响应纳米系统（HA-NSP），作为治疗脉络膜视网膜疾病（如年龄相关性黄斑变性（AMD）和糖尿病性视网膜病变）的潜在方法。AZP 纳米球通过凝聚技术制备，分散在 HA 水凝胶中，并通过红外光谱（FTIR）、X 射线衍射（XRD）和热重分析（TGA）进行表征。通过扫描电子显微镜（SEM）和动态光散射（DLS）研究其大小和形态，通过紫外光谱研究光响应性。研究了流变性能和可注射性，以及对 HRPE 细胞系的细胞毒性作用。通过 DLS 证实，粒径<200nm，对 365nmUV 的光响应性通过将粒径减小到 94nm 来确认。优化纳米球的包封效率为 85%，IgG 在 32 天内释放量达到 60%。通过流变学研究观察到最大力 10N 和剪切稀化行为，证实了 HA-NSP 的可注射性。两种 NSP 和 HA-NSP 的体外细胞毒性作用均显示非细胞毒性，相对细胞活力≥80%。成功开发了一种用于大分子 IgG 持续释放的生物相容性、可生物降解的可注射光响应纳米系统。
