Transfersome Hydrogel Containing 5-Fluorouracil and Etodolac Combination for Synergistic Oral Cancer Treatment

化学 Zeta电位 依托多拉克 药理学 动态光散射 毒品携带者 药品 分散性 色谱法 材料科学 医学 纳米技术 纳米颗粒 生物化学 有机化学
作者
Srivarsha Reddy Bollareddy,Vandana Krishna,Girdhari Roy,Deepika Dasari,Arti Dhar,Venkata Vamsi Krishna Venuganti
出处
期刊:Aaps Pharmscitech [Springer Science+Business Media]
卷期号:23 (2) 被引量:11
标识
DOI:10.1208/s12249-022-02221-z
摘要

Oral cancer is one of the most common malignancies with an increased rate of incidence. 5-Fluorouracil (5FU) is an effective chemotherapeutic indicated for oral cancer treatment. Etodolac (Et), a cyclooxygenase-2 inhibitor, can be used as an adjuvant agent to sensitize cancer cells to chemotherapy. The aim of this work was to prepare and characterize 5FU and Et dual drug-loaded transfersomes to treat oral cancer. Transfersomes were prepared by thin-film hydration method and characterized for the average particle size and zeta-potential using dynamic light scattering and scanning electron microscopy techniques. The prepared transfersomes were further characterized for their drug loading, entrapment efficiencies using amicon centrifuge tubes and drug release behavior using cellulose membrane. The synergistic activity of dual drug-loaded transfersomes was studied in FaDu oral cancer cells. Results showed that the average particle size, polydispersity index, and zeta potential were 91±6.4 nm, 0.28±0.03, and (-)46.9±9.5 mV, respectively, for 5FU- and Et (1:1)-loaded transfersomes. The highest encapsulation efficiency achieved was 36.9±3.8% and 79.8±6.4% for 5FU and Et (1:1), respectively. Growth inhibition studies in FaDu cells using different concentrations of 5FU and Et showed a combination index of 0.36, indicating a synergistic effect. The FaDu cell uptake of drug-loaded transfersomes was significantly (p<0.05) greater than that of free drugs. The transfersome hydrogel made of HPMC (2% w/w) showed similar flux, lag time, and permeation coefficient as that of drug-loaded transfersomes across excised porcine buccal tissue. In conclusion, 5FU and Et transfersome hydrogel can be developed for localized delivery to treat oral cancer.
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