Cheralayikkal Shamla, Manoj K, Safna Hussan K P
College of Pharmaceutical Sciences, Govt. Medical College, Kozhikode 673008, Kerala, India.
Department of Biochemistry, Amala Cancer Research Center, Thrissur, Kerala, India.
Heliyon. 2022 Jul 9;8(7):e09926. doi: 10.1016/j.heliyon.2022.e09926. eCollection 2022 Jul.
The conventional chemotherapeutic drugs have many side effects due to their non-selective tissue distribution, reduced drug concentration of the drug at the tumor site, and the drug resistance. To overcome these problems the chemotherapeutic agent should selectively accumulate the tumor site and stays there for a prolonged period of time releasing the payloads in a controlled manner. This can be achieved by the administration of a smart drug delivery system (SDDS) loaded with the active drug molecules. In this work, 5-fluorouracil (5-FU) is loaded into amine functionalised hollow mesoporous silica nanoparticles (HMSN-NH) and then coated with a biocompatible polydopamine (PDA) to formulate SSDS for 5-FU for pH-sensitive drug release. The physiochemical properties were characterised; the structural morphology was observed by using optical microscope, scanning electron microscope and transmission electron microscope, chemical interaction between the drug and excipients were characterised from Fourier transform infrared spectroscopy, the entrapment efficiency of loaded drug and the pH-dependent drug release rate were evaluated using UV-visible spectroscopy. It was observed that, the drug is compatible with excipients by retaining all the characteristics peaks of 5-FU with negligible changes in the position in all physical mixtures. The PDA coated 5-FU loaded HMSN-NH also exhibits a nearly spherical and non-aggregated morphology. The release rate was showed to increase with increase in concentration of structure-directing agent (Triton X 100) in the rate of a maximum release at the end of 72 h in pH 4. The prepared novel PDA coated 5-FU HMSN-NH was found to be capable of delivering the anti-cancer drug 5-FU specifically at the tumor site in a pH-dependent stimuli-responsive manner. It also showed a controlled release for a period of 72 h. The enhanced cytotoxicity against HeLa cell line were found for the formulated SSD form.
传统化疗药物由于其非选择性的组织分布、肿瘤部位药物浓度降低以及耐药性等问题而具有许多副作用。为克服这些问题，化疗药物应选择性地在肿瘤部位蓄积，并在较长时间内以可控方式释放药物有效载荷。这可以通过给予负载活性药物分子的智能药物递送系统（SDDS）来实现。在本研究中，将5-氟尿嘧啶（5-FU）负载到胺官能化的中空介孔二氧化硅纳米颗粒（HMSN-NH）中，然后用生物相容性聚多巴胺（PDA）包覆，以制备用于5-FU的具有pH敏感药物释放功能的SSDS。对其理化性质进行了表征；使用光学显微镜、扫描电子显微镜和透射电子显微镜观察结构形态，通过傅里叶变换红外光谱表征药物与辅料之间的化学相互作用，使用紫外可见光谱评估负载药物的包封率和pH依赖性药物释放率。结果表明，在所有物理混合物中，药物与辅料相容，5-FU的所有特征峰均得以保留，峰位变化可忽略不计。PDA包覆的负载5-FU的HMSN-NH也呈现出近似球形且无聚集的形态。在pH 4条件下，释放速率随结构导向剂（Triton X 100）浓度的增加而增加，在72 h结束时达到最大释放速率。所制备的新型PDA包覆的5-FU HMSN-NH能够以pH依赖性刺激响应方式将抗癌药物5-FU特异性递送至肿瘤部位。它还显示出72 h的控释效果。对于所制备的SSD剂型，发现其对HeLa细胞系的细胞毒性增强。
