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

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Abstract

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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Funding

This work was financially supported by the Science and Engineering Research Board (SERB), India, under the Core Research Grant scheme (EMR/2016/005421) and BITS Pilani.

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  1. Srivarsha Reddy Bollareddy and Vandana Krishna contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad, Telangana State, 500078, India

    Srivarsha Reddy Bollareddy, Vandana Krishna, Girdhari Roy, Deepika Dasari, Arti Dhar & Venkata Vamsi Krishna Venuganti

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  1. Srivarsha Reddy Bollareddy
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  2. Vandana Krishna
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Contributions

S. R. B. performed the investigations, and experiments, and had written the original draft. V. K. participated in the investigations and methodology, performed the experiments, and had written the original draft. G. R. contributed to the design of experiments, preparation of transfersomes, and determination of encapsulation efficiency; D. D. designed the cell culture experiments; A. D. conceptualized the cell culture experiments and supervised the work; V. V. K. V. conceptualized the work, supported with funding and resources, revised the manuscript, and supervised the work.

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Correspondence to Venkata Vamsi Krishna Venuganti.

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Bollareddy, S.R., Krishna, V., Roy, G. et al. Transfersome Hydrogel Containing 5-Fluorouracil and Etodolac Combination for Synergistic Oral Cancer Treatment. AAPS PharmSciTech 23, 70 (2022). https://doi.org/10.1208/s12249-022-02221-z

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