Sapre Nidhi, Chakraborty Rusha, Purohit Poorvi, Bhat Suresh, Das Gaurav, Bajpe Sneha R
Symbiosis Centre for Nanoscience and Nanotechnology, Symbiosis International (Deemed University) (SIU) Pune India
National Centre for Cell Science Pune India
RSC Adv. 2020 Mar 23;10(20):11716-11726. doi: 10.1039/c9ra11019d. eCollection 2020 Mar 19.
Physiological stimulus-specific cargo release from nanoparticle carriers is a holy grail of drug delivery research. While the majority of such work is carried out with cell lines, widespread use of common mammalian model systems - mice and rats - is difficult due to the associated cost and regulatory restrictions. Here we use the inexpensive, easily reared, excellent genetic model system to test pH responsive cargo release from widely used mesoporous silica nanoparticles (MSNs) coated with pH sensitive polydopamine (PDA) and polyethylene glycol (PEG) polymers. We synthesized 650 ± 75 nm diameter PDA or PEG coated mesoporous silica nanoparticles loaded with a fluorescent dye and fed to individual adult flies. Subsequently, the passage of the particles were monitored through the fly gut. As in mammals, the fly intestine has multiple pH specific zones that are easily accessible for imaging and also genetic, biochemical or physiological manipulations. We observed that both the species of MSNs ruptured around the acidic (pH < 4.0) middle midgut of the flies. PEG coated particles showed sharper specificity of release in the acidic middle midgut of flies than the PDA coated ones and had less tendency to clump together. Our results clearly show that the gut can be used as a model to test pH responsive biocompatible materials . Our work paves the way for greater use of as an complete systemic model in drug delivery and smart materials research. It also suggests that such specific delivery of chemical/biological cargo can be exploited to study basic biology of the gut cells and their communication with other organs.
从纳米颗粒载体实现生理刺激特异性的药物释放是药物递送研究的圣杯。虽然大多数此类研究是在细胞系中进行的,但由于相关成本和监管限制,常见的哺乳动物模型系统(小鼠和大鼠)难以广泛应用。在此,我们使用这种廉价、易于饲养的优秀遗传模型系统,来测试从涂有pH敏感聚多巴胺(PDA)和聚乙二醇(PEG)聚合物的广泛使用的介孔二氧化硅纳米颗粒(MSN)中进行pH响应性药物释放。我们合成了直径为650±75nm、负载荧光染料的PDA或PEG包覆的介孔二氧化硅纳米颗粒,并喂食给成年果蝇个体。随后,监测颗粒在果蝇肠道中的通过情况。与哺乳动物一样,果蝇肠道有多个pH特异性区域,便于成像以及进行遗传、生化或生理操作。我们观察到,两种MSN在果蝇酸性(pH<4.0)的中肠中部附近都会破裂。PEG包覆的颗粒在果蝇酸性中肠中部的释放特异性比PDA包覆的颗粒更强,且聚集在一起的倾向更小。我们的结果清楚地表明,肠道可作为测试pH响应性生物相容性材料的模型。我们的工作为在药物递送和智能材料研究中更多地将果蝇用作完整的全身模型铺平了道路。这也表明,这种化学/生物药物的特异性递送可用于研究肠道细胞的基础生物学及其与其他器官的通讯。