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Evaluation of the Safety, Cell Migration, and Mucoadhesive Properties of a Mucoadhesive Polymer Blend in Human Oral Mucosa

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Abstract

The efficacy of active pharmaceutical ingredients (API) in compounded medications for oral mucosa greatly depends on the composition of the base. Here, we assessed the safety, facilitation of cell migration, and mucoadhesive properties of a newly developed mucoadhesive polymer blend (MPB) which contains pullulan, tamarindus indica polysaccharide, and sodium hyaluronate. No cell death was observed when human oral keratinocyte (HOK) and fibroblast (HOrF) cells were exposed to 1% MPB for 24 h. Epithelial cells in a 3D buccal tissue model (EpiOral) were unaffected when exposed to 50% MPB for 20 h whereas 1% Triton X-100 killed 93% cells after 4.5 h. The expressions of cytokines IL1α and IL1β and cell proliferation markers PCNA, CYCLIN A, and CYCLIN D1 in EpiOral tissue did not increase suggesting that MPB is neither an irritant nor a mitogen. Markers of apoptosis such as cleavage of CASPASES 8/9, upregulation of pro-apoptosis NOXA protein, and downregulation of anti-apoptosis XIAP protein were observed in Triton X-100-treated cells but not in cells exposed to MPB. The migration of HOK and HOrF cells was stimulated by MPB, and the expression of E-CADHERIN in the EpiOral tissues was unaffected. Moreover, MPB showed stronger mucoadhesion on the human EpiOral tissue model compared with a reference product. We conclude that MPB can safely deliver API within the oral mucosa, facilitate cell migration, and may increase drug efficacy through its strong mucoadhesive property.

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REFERENCES

  1. Ahuja A, Khar RK, Ali J. Mucoadhesive drug delivery systems. Drug Dev Ind Pharm. 1997;23:489–515.

    Article  CAS  Google Scholar 

  2. Bruschi M, Freitas O. Oral bioadhesive drug delivery system. Drug Dev Ind Pharm. 2005;31:293–310.

    Article  CAS  PubMed  Google Scholar 

  3. Boddupalli BM, Mohammed ZNK, Nath RA, Banji D. Mucoadhesive drug delivery system: An overview. J Adv Pharm Technol Res. 2010;2:381–7.

    Article  Google Scholar 

  4. Giannola LI, Caro VD, Giandalia G, et al. A. Current status in buccal drug delivery. Pharm Technol Eur. 2008;20:32-6–8–9.

    Google Scholar 

  5. Hao J, Heng P. Buccal delivery systems. Drug Dev Ind Pharm. 2003;29:821–32.

    Article  CAS  PubMed  Google Scholar 

  6. Salamat N, Chittchang M, Johnston T. The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev. 2005;57:1666–91.

    Article  Google Scholar 

  7. Shojaei AH. Buccal mucosa as a route for systemic drug delivery: A review. J Pharm Pharm Sci. 1998;1:15–30.

    CAS  PubMed  Google Scholar 

  8. Koschier F, Kostrubsky V, Toole C, Galio MA. In vitro effects of ethanol and mouthrinse on permeability in an oral buccal mucosa tissue construct. Food Chem Toxicol. 2011;49:2524–9.

    Article  CAS  PubMed  Google Scholar 

  9. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.

    Article  CAS  PubMed  Google Scholar 

  10. Klausner M, Ayehunie S, Breyfogle BA, Wertz PW, Bacca L, Kubilus J. Organotypic human oral tissue models for toxicological studies. Toxicol in Vitro. 2007;21:938–49.

    Article  CAS  PubMed  Google Scholar 

  11. Moharamzadeh K, Franklin KL, Brook IM, van Noort R. Biologic assessment of antiseptic mouthwashes using a three-dimensional human oral mucosal model. J Periodontol. 2009;80:769–75.

    Article  CAS  PubMed  Google Scholar 

  12. Valdez BC, Li Y, Murray D, Champlin RE, Andersson BS. The synergistic cytotoxicity of clofarabine, fludarabine and busulfan in AML cells involves ATM pathway activation and chromatin remodeling. Biochem Pharmacol. 2011;81:222–32.

    Article  CAS  PubMed  Google Scholar 

  13. Gough W, Hulkower KI, Lynch R, McGlynn P, Uhlik M, Yan L, et al. A quantitative, facile, and highthroughput image-based cell migration method is a robust alternative to the scratch assay. J Biomol Screen. 2011;16:155–63.

    Article  PubMed  Google Scholar 

  14. Cohen GM. Caspases: the executioners of apoptosis. Biochem J. 1997;326:1–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Deveraux QL, Takahashi R, Salvesen GS, Reed JC. X-linked IAP is a direct inhibitor of cell-death proteases. Nature. 1997;388:300–4.

    Article  CAS  PubMed  Google Scholar 

  16. Ploner C, Kofler R, Villunger A. Noxa: at the tip of the balance between life and death. Oncogene. 2008;27:S84–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998;273:5858–68.

    Article  CAS  PubMed  Google Scholar 

  18. Maga G, Hubscher U. Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci. 2003;116:3051–60.

    Article  CAS  PubMed  Google Scholar 

  19. Lukas J, Bartkova J, Bartek J. Convergence of mitogenic signaling cascades from diverse classes of receptors at the cyclin D-cyclin-dependent kinase-pRb-controlled G1 checkpoint. Mol Cell Biol. 1996;16:6917–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Roguet R. Use of skin cell cultures for in vitro assessment of corrosion and cutaneous irritancy. Cell Biol Toxicol. 1999;15:63–75.

    Article  CAS  PubMed  Google Scholar 

  21. Warren R, Schwartz J, Sanders L, Juneja P. Attenuation of surfactant-induced interleukin 1α and expression by zinc pyrithione. Exog Dermatol. 2003;2:23–7.

    Article  CAS  Google Scholar 

  22. Thakur RA, Michniak BB, Meidan VM. Transdermal and buccal delivery of methylxanthines through human tissue in vitro. Drug Dev Ind Pharm. 2007;33:513–21.

    Article  CAS  PubMed  Google Scholar 

  23. Lambros MP, Parsa C, Mulamalla HC, et al. Identifying cell and molecular stress after radiation in a three-dimensional (3-d) model of oral mucositis. Biochem Biophys Res Commun. 2011;405:102–6.

    Article  CAS  PubMed  Google Scholar 

  24. Yadev NP, Murdoch C, Saville SP, Thornhill MH. Evaluation of tissue engineered models of the oral mucosa to investigate oral candidiasis. Microb Pathog. 2011;50:278–85.

    Article  CAS  PubMed  Google Scholar 

  25. Sridevi U, Jain A, Nagalaxmi V, Kumar UV, Goyal S. Expression of E-cadherin in normal oral mucosa, in oral precancerous lesions and in oral carcinomas. Eur J Dent. 2015;9:364–72.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kumar D, Saimi N, Pandit V, Ali S. An insight to pullulan: a biopolymer in pharmaceutical approaches. Int J Basic Appl Sci. 2012;1:202–19.

    Google Scholar 

  27. Xi K, Tabat Y, Uno K, Yoshimoto M, Kishida T, Sokawa Y, et al. Liver targeting of interferon through pullulan conjugation. Pharm Res. 1996;13:1846–50.

    Article  CAS  PubMed  Google Scholar 

  28. Scomparin A, Salmaso S, Bersani S, Satchi-Fainaro R, Caliceti P. Novel folated and non-folated pullulan bioconjugates for anti-cancer drug delivery. Eur J Pharm Sci. 2011;42:547–58.

    Article  CAS  PubMed  Google Scholar 

  29. Takahashi Y, Takeda C, Seto I, Kawano G, Machida Y. Formulation and evaluation of lactoferrin bioadhesive tablets. Int J Pharm. 2007;3:220–7.

    Article  Google Scholar 

  30. Law CH, Li JM, Cho HC, Chen YH, Chan HL. Hyaluronic acid-dependent protection in H9C2 cardiomyocytes; a cell model of heart ischemia-reperfusion injury and treatment. Toxicology. 2013;303:54–71.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Professional Compounding Centers of America, 9901 South Wilcrest Drive, Houston, Texas, 77099, USA

    Guiyun Song, Daniel Banov & August S. Bassani

  2. Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, University of Texas, 1515 Holcombe Blvd, Houston, Texas, 77030, USA

    Benigno C. Valdez

Authors
  1. Guiyun Song
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  2. Daniel Banov
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  3. August S. Bassani
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  4. Benigno C. Valdez
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Correspondence to Guiyun Song.

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Song, G., Banov, D., Bassani, A.S. et al. Evaluation of the Safety, Cell Migration, and Mucoadhesive Properties of a Mucoadhesive Polymer Blend in Human Oral Mucosa. AAPS PharmSciTech 18, 1617–1623 (2017). https://doi.org/10.1208/s12249-016-0630-z

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  • DOI: https://doi.org/10.1208/s12249-016-0630-z

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