载 5-氟尿嘧啶的聚合物电纺纳米纤维的配方、表征及细胞毒性研究——用于皮肤癌的治疗。

Formulation, Characterization and Cytotoxicity of 5-Fluorouracil Loaded Polymeric Electrospun Nanofibers for the Treatment of Skin Cancer.

机构信息

Ramanbhai Patel College of Pharmacy, Charotar University of Science Technology, Changa, Anand, Gujarat, India.

出版信息

Recent Pat Nanotechnol. 2019;13(2):114-128. doi: 10.2174/1872210513666190314095643.

DOI:10.2174/1872210513666190314095643

PMID:30868972

Abstract

BACKGROUND

The purpose of this study was to formulate, characterize and conduct in vitro cytotoxicity of 5-fluorouracil loaded polymeric electrospun nanofibers for the treatment of skin cancer. The patents on electrospun nanofibers (US9393216B2), (US14146252), (WO2015003155A1) etc. helped in the selection of polymers and method for the preparation of nanofibers.

METHODS

In the present study, the fabrication of nanofibers was done using a blend of chitosan with polyvinyl alcohol and processed using the electrospinning technique. 5-fluorouracil with known chemotherapeutic potential in the treatment of skin cancer was used as a drug carrier. 24-1 fractional factorial screening design was employed to study the effect of independent variables like the concentration of the polymeric solution, applied voltage (kV), distance (cm), flow rate (ml / hr) on dependent variables like % entrapment efficiency and fiber diameter.

RESULTS

Scanning electron microscopy was used to characterize fiber diameter and morphology. Results showed that the fiber diameter of all batches was found in the range of 100-200 nm. The optimized batch results showed the fiber diameter of 162.7 nm with uniform fibers. The tensile strength obtained was 190±37 Mpa. Further in vitro and ex vivo drug release profile suggested a controlled release mechanism for an extended period of 24 hr. The 5-fluorouracil loaded electrospun nanofibers were found to decrease cell viability up to ≥50% over 24 hr, with the number of cells dropping by ~ 10% over 48 hr. As the cell viability was affected by the release of 5-fluorouracil, we believe that electrospun nanofibers are a promising drug delivery system for the treatment of Basal Cell Carcinoma (BCC) skin cancer.

CONCLUSION

These results demonstrate the possibility of delivering 5-Fluorouracil loaded electrospun nanofiber to skin with enhanced encapsulation efficiency indicating the effectiveness of the formulation for the treatment of basal cell carcinoma type of skin cancer.

摘要

背景

本研究的目的是制备、表征和进行载有 5-氟尿嘧啶的聚合物电纺纳米纤维的体外细胞毒性实验，以治疗皮肤癌。电纺纳米纤维的专利（US9393216B2）、（US14146252）、（WO2015003155A1）等帮助选择聚合物和纳米纤维的制备方法。

方法

在本研究中，使用壳聚糖与聚乙烯醇的混合物通过电纺技术制备纳米纤维。将具有已知在皮肤癌治疗中化学治疗潜力的 5-氟尿嘧啶用作药物载体。采用 24-1 分数阶因子筛选设计来研究独立变量（如聚合物溶液浓度、施加电压（kV）、距离（cm）、流速（ml/hr））对依赖变量（如包封效率和纤维直径）的影响。

结果

扫描电子显微镜用于表征纤维直径和形态。结果表明，所有批次的纤维直径均在 100-200nm 范围内。优化批结果显示纤维直径为 162.7nm，纤维均匀。获得的拉伸强度为 190±37Mpa。进一步的体外和离体药物释放曲线表明，在 24 小时内可实现延长的控制释放机制。载有 5-氟尿嘧啶的电纺纳米纤维在 24 小时内使细胞活力降低至≥50%，48 小时内细胞数量减少约 10%。由于细胞活力受到 5-氟尿嘧啶释放的影响，我们相信电纺纳米纤维是治疗基底细胞癌（BCC）皮肤癌的有前途的药物输送系统。