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Thermosensitive and mucoadhesive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan for the treatment of oral squamous cell carcinoma

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Abstract

Buccal drug administration may be chosen as a medication route to treat various diseases for local or systemic effects. This study proposes the development of a thermosensitive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan to increase mucoadhesion, circumventing several limitations of this route of administration. Hydroxypropylmethylcellulose and Poloxamer® 407 were incorporated for hydrogel production. Physicochemical characterization parameters, such as particle size distribution, mean diameter, polydispersity index, zeta potential, and morphology, were analyzed. Spherical homogeneous particles were obtained with average diameter, of 173 ± 22 nm for LNCc (curcumin lipid-core nanocapsules) and 179 ± 48 nm for CLNCc (chitosan-curcumin lipid-core nanocapsules). A PDI equal to 0.09 ± 0.02 for LNCc and 0.26 ± 0.01 for CLNCc confirmed homogeneity. Tensile analysis and washability test on porcine buccal mucosa indicated higher mucoadhesion for hydrogels in comparison to the nanocapsules in suspension, remaining on the mucous membrane up to 8 h (10.92 ± 3.95 µg of curcumin washed for H-LNCc and 28.41 ± 24.47 µg for H-CLNCc) versus the latter, which remained washed on the membrane for 90 min only (62.60 ± 4.72 µg for LNCc and 52.08 ± 1.63 µg for CLNCc). The irritant potential (IR) of the formulations was evaluated by the hen’s egg chorioallantoic membrane test (HET-CAM), with no irritation phenomena observed. Formulations were tested for their efficacy in an in vitro model against oral squamous cancer cell line, showing a significant reduction in cell viability on all tested groups. These findings demonstrated that the proposed nanosystem is mucoadhesive and has potential to deliver buccal treatments.

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Abbreviations

LNCc:

Curcumin lipid-core nanocapsules

CLNCc:

Chitosan-curcumin lipid-core nanocapsules

CLNC:

Chitosan-coated lipid-core nanocapsules

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Acknowledgements

The authors would like to thank the Avian Facility for Teaching and Research (Department of Zootechnics, UFRGS, Porto Alegre, Brazil) and Slaughterhouse Ouro Do Sul for donating the chicken eggs and porcine buccal mucosa, respectively. The authors would also like to thank Professor César Petzhold and Grasiela Gheno, from the Department of Organic Chemistry of the Institute of Chemistry at Universidade Federal do Rio Grande do Sul, for their collaboration in the operation of the rheometer and for the assistance in analyzing the data of the rheology test.

Funding

This study was supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul – FAPERGS (ARD 17/2551–0000-838–3). Moreover, this study was financed partially by the Conselho Nacional de Desenvolvimento Científico e Tecnológico–CNPQ. Ana Ortega thanks the Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES—for her fellowship.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, 90610-000, Brazil

    Ana Ortega, Ayana Brêtas da Silva, Kelly Cristine Zatta, Giovana Ravizzoni Onzi, Silvia Stanisçuaski Guterres & Karina Paese

  2. Programa de Pós-Graduação em Nanotecnologia Farmacêutica, UFRGS, Porto Alegre, 90610-000, Brazil

    Leidyana Moraes da Costa & Silvia Stanisçuaski Guterres

  3. Embrapa Suínos e Aves, 89715-899, Concórdia, Brazil

    Francisco Noé da Fonseca

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  1. Ana Ortega
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Ortega, A., da Silva, A.B., da Costa, L.M. et al. Thermosensitive and mucoadhesive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan for the treatment of oral squamous cell carcinoma. Drug Deliv. and Transl. Res. 13, 642–657 (2023). https://doi.org/10.1007/s13346-022-01227-1

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