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Curcumin-Loaded Chitosan-Coated 5-Fluorouracil Encapsulated Nanozeolitic Imidazolate Framework for Combination Cancer Therapy

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Abstract

Background

5-Fluorouracil (5-FU) is a good anti-cancer drug, but its prolonged use results in overexpression of certain enzymes like thymidylate synthase and causes multidrug resistance in cancer cells. Many studies proven that a combination of curcumin (CUR) and 5-FU can overcome the above difficulties. It was in this direction that a novel material that could reversibly bind with drug molecules was designed and developed to overcome drug resistance.

Methods

ZIF-8 was surface modified with nitro groups (NZIF-8); 5-FU was encapsulated in the NZIF-8 through one pot method. Nitro groups on the surface of NZIF-8 enable coating of curcumin loaded chitosan, thereby forming CUR-loaded chitosan-coated 5-FU encapsulated NZIF-8 (CUR-loaded CS-coated 5-FU@NZIF-8). The drug loading and in vitro drug release studies were conducted using UV–Visible spectrophotometry at 266 nm for 5-FU and 425 nm for CUR, respectively.

Results

The nanocarrier exhibited an average size of 60 nm and was highly stable as indicated by thermogravimetric studies. The residual positive charge imparted by the amino groups on chitosan enabled enhanced cellular uptake and maybe responsible for the enhanced cytotoxicity of 5-FU + CUR combination in MCF-7 breast cancer cells (83.2%) compared to that of individual drug treatment without the nanocarrier (67.7%).

Conclusion

The study demonstrates the capability of CUR-loaded CS-coated 5-FU@NZIF-8 for combination therapy to overcome drug resistance. The results obtained from MTT assay suggest the potential applicability of the present material in the sustained delivery of simultaneous drugs. This approach can further improve efficacy as well as the cost effectiveness of chemotherapy.

Graphical Abstract

Schematic representation of combination therapy using CUR-loaded CS-coated 5-FU@NZIF-8

Highlights

  • A dual drug delivery system was used in which CUR-loaded chitosan-coated 5-FU encapsulated nitro modified ZIF-8 was synthesized for combination therapy.

  • The surface of ZIF-8 was modified with nitro groups which enables effective coating of chitosan.

  • In a tumor environment, which is acidic in nature, chitosan swells thereby CUR releases quickly, while due to chitosan coating the encapsulated 5-FU releases slowly.

  • The positively charged amino group on the surface of chitosan helps for targeted delivery since tumor cell surface is negatively charged.

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Authors and Affiliations

  1. Department of Chemistry, Sree Narayana College, Alathur Palakkad, 678682, Kerala, India

    Jiju Kazhani Radhakrishnan

  2. Department of Chemistry, Sree Narayana College, Chempazhanthy, Thiruvananthapuram, 695587, Kerala, India

    Subhadra Suma

  3. Department of Chemistry, NSS College, Nemmara, Palakkad, 678508, Kerala, India

    Anoop Somasekharan Nair

  4. Department of Chemistry, Sree Narayana College, Chengannur, Alappuzha, 689508, Kerala, India

    Reshmi Ramachandran

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Radhakrishnan, J., Suma, S., Nair, A. et al. Curcumin-Loaded Chitosan-Coated 5-Fluorouracil Encapsulated Nanozeolitic Imidazolate Framework for Combination Cancer Therapy. J Pharm Innov 18, 2043–2053 (2023). https://doi.org/10.1007/s12247-023-09770-1

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