Singam Amarnath, Killi Naresh, Patel Pratikshkumar R, Gundloori Rathna V N
Polymer Science and Engineering, CSIR-National Chemical Laboratory Homi Bhabha Road Pune-411008 Maharashtra India
Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India.
RSC Adv. 2021 Nov 8;11(49):30532-30543. doi: 10.1039/d1ra04242d. eCollection 2021 Sep 14.
Natural polymers provide a better alternative to synthetic polymers in the domain of drug delivery systems (DDSs) because of their renewability, biocompatibility, and low immunogenicity; therefore, they are being studied for the development of bulk/nanoformulations. Likewise, current methods for engineering natural polymers into micelles are in their infancy, and in-depth studies are required using natural polymers as controlled DDSs. Accordingly, in our present study, a new micellar DDS was synthesized using ethyl cellulose (EC) grafted with polyethylene glycol (PEG); it was characterized, its properties, cell toxicity, and hemocompatibility were evaluated, and its drug release kinetics were demonstrated using doxorubicin (DOX) as a model drug. Briefly, EC was grafted with PEG to form the amphiphilic copolymers EC-PEG1 and EC-PEG2 with varying PEG concentrations, and nano-micelles were prepared with and without the drug (DOX) a dialysis method; the critical micelle concentrations (CMCs) were recorded to be 0.03 mg mL and 0.00193 mg mL for EC-PEG1 and EC-PEG2, respectively. The physicochemical properties of the respective nano-micelles were evaluated various characterization techniques. The morphologies of the nano-micelles were analyzed transmission electron microscopy (TEM), and the average size of the nano-micelles was recorded to be ∼80 nm. , drug release studies were done for 48 h, where 100% DOX release was recorded at pH 5.5 and 52% DOX release was recorded at pH 7.4 from the micelles. In addition, cytotoxicity studies suggested that DOX-loaded micelles were potent in killing MDA-MB-231 and MCF-7 cancer cells, and the blank micelles were non-toxic toward cancerous and normal cells. A cellular uptake study fluorescence microscopy indicated the internalization of DOX-loaded micelles by cancer cells, delivering the DOX into the cellular compartments. Based on these studies, we concluded that the developed material should be studied further studies to understand its potential as a controlled DDS to treat cancer.
在药物递送系统(DDSs)领域,天然聚合物因其可再生性、生物相容性和低免疫原性,为合成聚合物提供了更好的替代品;因此,人们正在研究将其用于开发块状/纳米制剂。同样,目前将天然聚合物加工成胶束的方法尚处于起步阶段,需要对使用天然聚合物作为可控药物递送系统进行深入研究。因此,在我们目前的研究中,合成了一种新的胶束药物递送系统,该系统使用接枝了聚乙二醇(PEG)的乙基纤维素(EC);对其进行了表征,评估了其性质、细胞毒性和血液相容性,并以阿霉素(DOX)作为模型药物展示了其药物释放动力学。简要地说,将EC与PEG接枝,形成具有不同PEG浓度的两亲共聚物EC-PEG1和EC-PEG2,并采用透析法制备含药(DOX)和不含药的纳米胶束;记录到EC-PEG1和EC-PEG2的临界胶束浓度(CMC)分别为0.03 mg/mL和0.00193 mg/mL。使用各种表征技术评估了各自纳米胶束的物理化学性质。通过透射电子显微镜(TEM)分析了纳米胶束的形态,记录到纳米胶束的平均尺寸约为80 nm。此外,进行了48小时的药物释放研究,在pH 5.5时记录到胶束中DOX的释放率为100%,在pH 7.4时记录到DOX的释放率为52%。此外,细胞毒性研究表明,载有DOX的胶束对杀死MDA-MB-231和MCF-7癌细胞有效,而空白胶束对癌细胞和正常细胞无毒。通过荧光显微镜进行的细胞摄取研究表明,载有DOX的胶束被癌细胞内化,将DOX递送至细胞区室。基于这些研究,我们得出结论,应进一步开展研究,以了解所开发材料作为治疗癌症的可控药物递送系统的潜力。