Abstract
This study aimed to produce a Poloxamer 407/Chitosan polymeric system for the controlled release of α-TOC and evaluate its biological properties using normal oral keratinocytes. The production of the polymeric controlled release system involved loading of α-TOC and micellization of the isotropic P407 phase with subsequent encapsulation with chitosan. The chitosan coverage of the micelles was confirmed by the positive zeta potential (+ 12.8 mV). The micelles (TOC-P407-CH) developed had average particle sizes of 193.8 ± 51.0 nm (PDI 0.502 ± 0.068) (α-TOC 50 mg/mL—TOC50-P407-CH) and 714.5 ± 110.18 nm (PDI 0.886 ± 0.196) (α-TOC 200 mg/mL—TOC200-P407-CH) (P = 0.0018) with irregular morphology. The release test by UV–Vis demonstrated a slow and controlled release for TOC50-P407-CH (initial release peak of 82% after the first 5 h). The α-TOC-loaded micelles did not show any cytotoxicity in vitro (P > 0.05). Also, they promoted superior cell proliferation in NOE cells (P < 0.001). This study shows that a controlled release system developed with 50 mg/mL α-TOC has the potential to be used in epithelial cell regeneration.
Graphical abstract
Similar content being viewed by others
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
H. Yan, Z. **, W. **, Y. Zhong, H. Ai, Y. Wu, Q. Xu, X. Bai, D. Liu, W. Nie, Y. Zuo, A systematic review and meta-analysis of acupuncture treatment for oral ulcer. Medicine 99(29), e21314–e21318 (2020)
E. Kürklü-gürleyen, M. Ögüt-Erişen, O. Çakır, Ö. Uysal, G. Ak, Quality of life in patients with recurrent aphthous stomatitis treated with a mucoadhesive patch containing citrus essential oil. Patient Prefer Adher. 10, 967–973 (2016)
S.G. Fitzpatrick, D.M. Cohen, A.N. Clark, Lesões Ulceradas da Mucosa Oral: Revisão Clínica e Histológica. Head Neck Pathol. 13(1), 91–102 (2019)
G. Daugėlaitė, K. Užkuraitytė, E. Jagelavičienė, A. Filipauskas, Prevention and Treatment of Chemotherapy and Radiotherapy Induced Oral Mucositis. Medicina 55(2), 25 (2019)
H.Y. Sroussi, J.B. Epstein, R.-J. Bensadoun, D.P. Saunders, R.V. Lalla, C.A. Migliorati et al., Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med. 6, 2918–2931 (2017)
L.F. Cuba, A.B. Filho, K. Cherubini, F.G. Salum, M.A.Z. Figueiredo, Topical application of Aloe vera and vitamin E on induced ulcers on the tongue of rats subjected to radiation: clinical and histological evaluation. Support Care Cancer. 24, 2557–2564 (2016)
V. Saez, I.D.L. Souza, C.R.E. Mansur, Lipid Nanoparticles (SLN & NLC) for delivery of vitamin E: a comprehensive review. Int. J. Cosmet. Sci. 40, 103–116 (2018)
C. Caddeo, M.L. Manca, J.E. Peris, I. Usach, M. Matos, X. Fernàndez-busquets et al., Tocopherol-loaded transfersomes: in vitro antioxidant activity and efficacy in skin regeneration. Int. J. Pharm. 15, 34–41 (2018)
Y. Horikoshi, K. Kamizaki, T. Hanaki1, M. Morimoto, Y. Kitagawa, K. Nakaso, et al. α-Tocopherol promotes HaCaT keratinocyte wound repair through the regulation of polarity proteins leading to the polarized cell migration. Biofactors. 44, 180–91(2018).
P.B. Shekhawat, V.B. Pokharkar, Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles. Acta Pharm. Sin. B 7(3), 260–280 (2017)
R.G. Saratale, H.S. Lee, Y.E. Koo, G.D. Saratale, Y.J. Kim, J.Y. Imm, Y. Park, Absorption kinetics of vitamin E nanoemulsion and green tea microstructures by intestinal in situ single perfusion technique in rats. Food Res. Int. 106, 149–155 (2018)
A.A. Sultan, S.A. El-gizawy, M.A. Osman, G.M. Maghraby, Self dispersing mixed micelles forming systems for enhanced dissolution and intestinal permeability of hydrochlorothiazide. Colloids Surf. B 149, 206–216 (2017)
M. Almeida, M. Magalhães, F. Veiga et al., Poloxamers, poloxamines and polymeric micelles: definition, structure and therapeutic applications in cancer. J. Polym. Res. 25, 31 (2018)
L. Ci, Z. Huang, Y. Liu, Z. Liu, G. Wei, W. Lu, Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: preparation, characterization and application in a vaginal drug delivery system. Acta. Pharm. Sin. B 7(5), 593–602 (2017)
G. Leyva-Gómez, E. Santillan-Reyes, E. Lima, A. Madrid-Martínez, E. Krötzsch, D. Quintanar-Guerrero et al., A novel hydrogel of poloxamer 407 and chitosan obtained by gamma irradiation exhibits physicochemical properties for wound management. Mater. Sci. Eng. C 74, 36–46 (2017)
A.A. Menazea, A.M. Ismail, N.S. Awwad, H.A. Ibrahium, Physical characterization and antibacterial activity of PVA/Chitosan matrix doped by selenium nanoparticles prepared via one-pot laser ablation route. J. Mater. Res. Technol. 9(5), 9598–9606 (2020)
Q. Ma, Y. Gao, W. Sun, J. Cao, Y. Liang, S. Han, X. Wang, Y. Sun, Self-Assembled chitosan/phospholipid nanoparticles: from fundamentals to preparation for advanced drug delivery. Drug Deliv. 27(1), 200–215 (2020)
C. Saikia, P. Gogoi, T.K. Maji, Journal of molecular and genetic chitosan: a promising biopolymer in drug delivery applications. J. Mol. Genet. Med. 4, 1–10 (2015)
T. Gratieri, G. Martins, E. Melani, V. Hugo, O. Freitas, R. Fonseca et al., A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery. Eur. J. Pharm. Biopharm. 75(2), 186–193 (2010)
K. Kesavan, S. Kant, P.N. Singh, J.K. Pandit. Mucoadhesive Chitosan-Coated Cationic Microemulsion of Dexamethasone for Ocular Delivery: In Vitro and In Vivo Evaluation. Curr Eye Res. 38(3),342–52(2013).
N.Varga, Á. Turcsányi, V. Hornok, E. Csapó. Vitamin E-loaded PLA- and PLGA-based core-shell nanoparticles: synthesis, structure optimization and controlled drug release. Pharmaceutics 1357–1371 (2019)
P. Kumar, A. Nagarajan, P.D. Uchil, Analysis of Cell Viability by the MTT Assay. Cold Spring Harb Protoc. 6, 469–472 (2018)
M.R. Dourado, J. Korvala, P. Åström, C.E. Oliveira, N.K. Cervigne, L.S. Mofatto et al., Extracellular vesicles derived from cancer-associated fibroblasts induce the migration and invasion of oral squamous cell carcinoma. J. Extracell Vesicles. 8, 1578525 (2019)
A.E. Al Moustafa, W.D. Foulkes, N. Benlimame, A. Wong, L. Yen, J. Bergeron, et al. E6/E7 proteins of HPV type 16 and ErbB-2 cooperate to induce neoplastic transformation of primary normal oral epithelial cells. Oncogene. 23(2),350(2004).
A.A. El-Housseiny, S.M. Saleh, A.A. El-Masry, A.A. Allam, Children receiving chemotherapy. J. Pediatr. Dent. 31, 167–170 (2007).
D.K. Sener, M. Aydin, S. Cangur, E. Guven, The effect of oral care with Chlorhexidine, Vitamin E and honey on mucositis in pediatric intensive care patients : a randomized controlled trial. J. Pediatr. Nurs. 45, e95-101 (2019)
R. Basak, R. Bandyopadhyay, Encapsulation of hydrophobic drugs in Pluronic F127 micelles: effects of drug hydrophobicity, solution temperature, and pH. Langmuir 29(13), 4350–4356 (2013)
P.K. Singh, V.K. Pawar, A.K. Jaiswal, Y. Singh, C.H. Srikanth, M. Chaurasia et al., Chitosan coated PluronicF127 micelles for effective delivery of Amphotericin B in Experimental Visceral Leishmaniasis. Int. J. Biol. Macromol. 105, 1220–1231 (2017)
S. Alexander, T. Cosgrove, T.C. Castle, I. Grillo, S.W. Prescott, Effect of temperature, cosolvent, and added drug on pluronic—flurbiprofen micellization. J. Phys. Chem. B 116, 11545–11551 (2012)
I.G. Zigoneanu, C.E. Astete, C.M. Sabliov, Nanoparticles with entrapped α-tocopherol: synthesis, characterization, and controlled release. Nanotechnology 19, 10506–10515 (2008)
Y. Luo, B. Zhang, M. Whent, L.L. Yu, Q. Wang, Preparation and characterization of zein/chitosan complex for encapsulation of α-tocopherol, and its in vitro controlled release study. Colloids Surf. B 85(2), 145–152 (2011)
M.C. Bonferoni, F. Riva, A. Invernizzi, E. Dellera, G. Sandri, S. Rossi, et al. Alpha tocopherol loaded chitosan oleate nanoemulsions for wound healing. Evaluation on cell lines and ex vivo human biopsies, and stabilization in spray dried Trojan microparticles. Eur. J. Pharm. Biopharm. 123, 31–41 (2017).
Y. Liu, S. FU, L. Lin, Y. Cao, X. **e, H. Yu, et al. Redox-sensitive Pluronic F127-tocopherol micelles: synthesis , characterization, and cytotoxicity evaluation. Int. J. Nanomed. 12, 2635–44 (2017).
P. Dubey, S.A. Barker, D.Q.M. Craig, Design and characterization of cyclosporine A-loaded nano fibers for enhanced drug dissolution. ACS Omega 5(2), 1003–1013 (2020)
J. He, H. Shi, S. Huang, L. Han, W. Zhang, Core-shell nanoencapsulation of α-tocopherol by blending sodium oleate and Rebaudioside A: preparation, characterization, and antioxidant activity. Molecules 23, 3183–3194 (2018)
N. Liang, S. Sun, X. Gong, Q. Li, P. Yan, F. Cui, Polymeric micelles based on modified glycol chitosan for paclitaxel delivery: preparation, characterization and evaluation. Int J Mol Sci. 19, 1550–1564 (2018)
E. Giuliano, D. Paolino, M. Fresta, D. Cosco, Mucosal applications of Poloxamer 407-based hydrogels: an overview. Pharmaceutics 10, 159–185 (2018)
Acknowledgments
We gratefully acknowledge the support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPQ (Inct Teranostica).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
de C. Coelho Junior, É., Maciel, P.P., de A. F. Muniz, I. et al. Poloxamer 407/chitosan micelles can improve α-Tocopherol effect on oral keratinocytes proliferation. Journal of Materials Research 36, 1447–1455 (2021). https://doi.org/10.1557/s43578-021-00169-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1557/s43578-021-00169-7