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Chitosan-Albumin Nanocomposite as a Promising Nanocarrier for Efficient Delivery of Fluconazole Against Vaginal Candidiasis

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Abstract

Currently, the high incidence of fungal infections among females has resulted in outstanding problems. Candida species is related with multidrug resistance and destitute clinical consequences. Chitosan-albumin derivatives with more stability exhibit innate antifungal and antibacterial effects that boost the activity of the drug without inflammatory impact. The stability and sustained release of Fluconazole in mucosal tissues can be ensured by encapsulating in protein/polysaccharide nanocomposites. Thus, we developed chitosan-albumin nanocomposite (CS-A) loaded with Fluconazole (Flu) antifungals against vaginal candidiasis. Various ratios of CS/Flu (1:1, 1:2, 2:1) were prepared. Thereafter, the CS-A-Flu nanocomposites were qualified and quantified using FT-IR, DLS, TEM, and SEM analytical devices, and the size range from 60 to 100 nm in diameter was attained for the synthesized nanocarriers. Afterward, the antifungal activity, biofilm reduction potency, and cell viability assay were performed for biomedical evaluation of formulations. The minimum inhibitory concentration) and minimum fungicidal concentration on Candida albicans were attained at 125 ng/μL and 150 ng/μL after treatment with a 1:2 (CS/Flu) ratio of CS-A-Flu. The biofilm reduction assay indicated that biofilm formation was between 0.05 and 0.1% for CS-A-Flu at all ratios. The MTT assay also exhibited excellent biocompatibility for samples, about 7 to 14% toxicity on human HGF normal cells. These data have indicated that CS-A-Flu would be a promising candidate against Candida albicans.

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Data Availability

The data that support the findings of this study are available on request from the corresponding author.

References

  1. MacAlpine, J., Robbins, N., & Cowen, L. E. (2022). Bacterial-fungal interactions and their impact on microbial pathogenesis. Molecular Ecology. https://doi.org/10.1111/mec.16411

  2. Carvalho, G. C., et al. (2021). Prevalence of vulvovaginal candidiasis in Brazil: A systematic review. Medical Mycology, 59(10), 946–957.

    Article  PubMed  Google Scholar 

  3. Palmeira-de-Oliveira, R., et al. (2022). Women’s preferences and acceptance for different drug delivery routes and products. Advanced Drug Delivery Reviews, 114133.

  4. Kumari, R., Sunil, D., & Ningthoujam, R. S. (2020). Hypoxia-responsive nanoparticle based drug delivery systems in cancer therapy: An up-to-date review. Journal of Controlled Release, 319, 135–156.

    Article  CAS  PubMed  Google Scholar 

  5. Naderlou, E., et al. (2020). Enhanced sensitivity and efficiency of detection of Staphylococcus aureus based on modified magnetic nanoparticles by photometric systems. Artificial Cells, Nanomedicine, and Biotechnology, 48(1), 810–817.

    Article  CAS  PubMed  Google Scholar 

  6. Narmani, A., & Jafari, S. M. (2021). Chitosan-based nanodelivery systems for cancer therapy: Recent advances. Carbohydrate Polymers, 272, 118464.

    Article  CAS  PubMed  Google Scholar 

  7. Chen, Y., et al. (2018). Evaluation of the PEG density in the PEGylated chitosan nanoparticles as a drug carrier for curcumin and mitoxantrone. Nanomaterials, 8(7), 486.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Niu, S., et al. (2019). A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy. Journal of Nanobiotechnology, 17(1), 1–18.

    Article  CAS  Google Scholar 

  9. Khakinahad, Y., et al. (2022). Margetuximab conjugated-PEG-PAMAM G4 nano-complex: A smart nano-device for suppression of breast cancer. Biomedical Engineering Letters, 12(3), 317.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wang, Y., et al. (2016). Nanoparticles of chitosan conjugated to organo-ruthenium complexes. Inorganic Chemistry Frontiers, 3(8), 1058–1064.

    Article  CAS  Google Scholar 

  11. Kong, M., et al. (2010). Antimicrobial properties of chitosan and mode of action: A state of the art review. International Journal of Food Microbiology, 144(1), 51–63.

    Article  CAS  PubMed  Google Scholar 

  12. Caraceni, P., et al. (2013). Clinical indications for the albumin use: Still a controversial issue. European Journal of Internal Medicine, 24(8), 721–728.

    Article  CAS  PubMed  Google Scholar 

  13. Kianfar, E. (2021). Protein nanoparticles in drug delivery: Animal protein, plant proteins and protein cages, albumin nanoparticles. Journal of Nanobiotechnology, 19(1), 159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ogawa, M., et al. (2014). Plasma antithrombin levels correlate with albumin and total protein in gestational hypertension and preeclampsia. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 4(2), 174–177.

    Article  Google Scholar 

  15. Parodi, A., et al. (2019). Albumin nanovectors in cancer therapy and imaging. Biomolecules, 9(6), 218.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wong, C. Y., Martinez, J., & Dass, C. R. (2016). Oral delivery of insulin for treatment of diabetes: Status quo, challenges and opportunities. Journal of Pharmacy and Pharmacology, 68(9), 1093–1108.

    Article  CAS  PubMed  Google Scholar 

  17. Walke, S., et al. (2015). Fabrication of chitosan microspheres using vanillin/TPP dual crosslinkers for protein antigens encapsulation. Carbohydrate Polymers, 128, 188–198.

    Article  CAS  PubMed  Google Scholar 

  18. El-Housiny, S., et al. (2018). Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: Formulation and clinical study. Drug Delivery, 25(1), 78–90.

    Article  CAS  PubMed  Google Scholar 

  19. Rençber, S., et al. (2019). Formulation and evaluation of fluconazole loaded oral strips for local treatment of oral candidiasis. Journal of Drug Delivery Science and Technology, 49, 615–621.

    Article  Google Scholar 

  20. Chayachinda, C., et al. (2022). Effect of intravaginal gentian violet for acute vaginal candidiasis treated with a single dose oral fluconazole: A randomised controlled trial. Journal of Obstetrics and Gynaecology, 42(6), 2190.

    Article  CAS  PubMed  Google Scholar 

  21. Kelidari, H. R., et al. (2017). Improved yeast delivery of fluconazole with a nanostructured lipid carrier system. Biomedicine & Pharmacotherapy, 89, 83–88.

    Article  CAS  Google Scholar 

  22. Faramarzi, N., et al. (2020). Synthesis and in vitro Evaluation of tamoxifen-loaded gelatin as effective nanocomplex in drug delivery systems. International Journal of Nanoscience, 19(5), 2050002.

    Article  CAS  Google Scholar 

  23. Cantón, E., et al. (2003). Minimum fungicidal concentrations of amphotericin B for bloodstream Candida species. Diagnostic Microbiology and Infectious Disease, 45(3), 203–206.

    Article  PubMed  Google Scholar 

  24. Fotouhi, P., et al. (2021). Surface modified and rituximab functionalized PAMAM G4 nanoparticle for targeted imatinib delivery to leukemia cells: In vitro studies. Process Biochemistry, 111, 221–229.

    Article  CAS  Google Scholar 

  25. Bandara, S., et al. (2018). Synthesis and characterization of Zinc/Chitosan-Folic acid complex. Heliyon, 4(8), e00737.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kaur, K., et al. (2015). Wheat germ agglutinin anchored chitosan microspheres of reduced brominated derivative of noscapine ameliorated acute inflammation in experimental colitis. Colloids and Surfaces B: Biointerfaces, 132, 225–235.

    Article  CAS  PubMed  Google Scholar 

  27. Tan, W., et al. (2018). Novel cationic chitosan derivative bearing 1, 2, 3-triazolium and pyridinium: Synthesis, characterization, and antifungal property. Carbohydrate Polymers, 182, 180–187.

    Article  CAS  PubMed  Google Scholar 

  28. El Rabey, H. A., et al. (2019). Augmented control of drug-resistant Candida spp. via fluconazole loading into fungal chitosan nanoparticles. International Journal of Biological Macromolecules, 141, 511–516.

    Article  PubMed  Google Scholar 

  29. Yousefi, M., Narmani, A., & Jafari, S. M. (2020). Dendrimers as efficient nanocarriers for the protection and delivery of bioactive phytochemicals. Advances in Colloid And Interface Science, 278, 102125.

    Article  CAS  PubMed  Google Scholar 

  30. Rezvani, M., et al. (2018). Synthesis and in vitro study of modified chitosan-polycaprolactam nanocomplex as delivery system. International Journal of Biological Macromolecules, 113, 1287–1293.

    Article  CAS  PubMed  Google Scholar 

  31. Narmani, A., et al. (2018). Targeting delivery of oxaliplatin with smart PEG-modified PAMAM G4 to colorectal cell line: In vitro studies. Process Biochemistry, 69, 178–187.

    Article  CAS  Google Scholar 

  32. Golafzani, F. N., et al. (2022). Delivery of miRNA-126 through folic acid-targeted biocompatible polymeric nanoparticles for effective lung cancer therapy. Journal of Bioactive and Compatible Polymers, 37(3), 168–188.

    Article  CAS  Google Scholar 

  33. Narmani, A., et al. (2020). Breast tumor targeting with PAMAM-PEG-5FU-99mTc as a new therapeutic nanocomplex: In in-vitro and in-vivo studies. Biomedical Microdevices, 22(2), 1–13.

    Article  Google Scholar 

  34. Fitaihi, R. A., et al. (2018). Role of chitosan on controlling the characteristics and antifungal activity of bioadhesive fluconazole vaginal tablets. Saudi Pharmaceutical Journal, 26(2), 151–161.

    Article  PubMed  Google Scholar 

  35. Tiboni, M., et al. (2021). 3D printed clotrimazole intravaginal ring for the treatment of recurrent vaginal candidiasis. International Journal of Pharmaceutics, 596, 120290.

    Article  CAS  PubMed  Google Scholar 

  36. Meng, Q., et al. (2021). An overview of chitosan and its application in infectious diseases. Drug Delivery and Translational Research, 11, 1340–1351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Li, L., et al. (2022). Amphiphilic nano-delivery system based on modified-chitosan and ovalbumin: Delivery and stability in simulated digestion. Carbohydrate Polymers, 294, 119779.

    Article  CAS  PubMed  Google Scholar 

  38. Calvo, N. L., et al. (2019). Chitosan-hydroxypropyl methylcellulose tioconazole films: A promising alternative dosage form for the treatment of vaginal candidiasis. International Journal of Pharmaceutics, 556, 181–191.

    Article  CAS  PubMed  Google Scholar 

  39. Silva-Dias, A., et al. (2014). Anti-biofilm activity of low-molecular weight chitosan hydrogel against Candida species. Medical Microbiology and Immunology, 203, 25–33.

    Article  CAS  PubMed  Google Scholar 

  40. Jabali, M. K., et al. (2022). Design of a pDNA nanocarrier with ascorbic acid modified chitosan coated on superparamagnetic iron oxide nanoparticles for gene delivery. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 632, 127743.

    Article  Google Scholar 

  41. Abdellatif, M. M., et al. (2020). Formulation and characterization of sertaconazole nitrate mucoadhesive liposomes for vaginal candidiasis. International Journal of Nanomedicine, 15, 4079.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Dara, P. K., et al. (2021). Biocompatibility and histopathological evaluation of chitosan nanoparticles grafted fish gelatin bio-nanocomposite membranes in rats. Iranian Polymer Journal, 30(9), 953–964.

    Article  CAS  Google Scholar 

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MHA: study concept and design, acquisition of data, drafting of the manuscript. JM: critical revision of the manuscript for important intellectual content. SK: statistical analysis, administrative, technical and material support, study supervision, analysis and interpretation of data.

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Correspondence to Sepideh Khaleghi.

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Hatamiazar, M., Mohammadnejad, J. & Khaleghi, S. Chitosan-Albumin Nanocomposite as a Promising Nanocarrier for Efficient Delivery of Fluconazole Against Vaginal Candidiasis. Appl Biochem Biotechnol 196, 701–716 (2024). https://doi.org/10.1007/s12010-023-04492-z

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