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Screening and In Vitro Evaluation of Mucoadhesive Thermoresponsive System Containing Methylene Blue for Local Photodynamic Therapy of Colorectal Cancer

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Abstract

Purpose

Photodynamic therapy (PDT) with methylene blue (MB) constitutes a potentially useful modality for colorectal cancer treatment. The limitations of the formulations containing MB are problems of administration and the inability to get the closeness contact at the site during the appropriate residence time. Present study aimed to develop and characterize mucoadhesive thermoresponsive system containing MB designed as platform for colorectal cancer therapy.

Methods

Formulations composed of different amounts of poloxamer 407 (Polox), Carbopol 934P (Carb), and MB were developed and characterized as rheological, compressional, mucoadhesive and syringeability properties, toxicity, photodynamic action, in vitro MB release profile, and ex vivo MB intestinal permeation.

Results

The different compositions resulted in formulations with distinctive macroscopic characteristics and wide range of gelation temperatures. The compressional flow, mucoadhesive, syringeability, and rheological properties were significantly influenced by temperature and/or composition. The MB release from formulation was governed by anomalous transport. In addition, it was observed that MB permeated the intestinal membrane; the formulation possesses photodynamic activity and low toxicity.

Conclusions

The data obtained from the system composed of 20% Polox, 0.15% Carb, and 0.25% MB indicated a potentially functional role in PDT of the colorectal cancer and suggest it is worthy of clinical evaluation.

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Abbreviations

ATCC:

American Type Culture Collection

Carb:

Carbopol 934P®

CRC:

Colorectal cancer

DMEM:

Dulbecco Modified Eagle’s Medium

DMF:

Dimethylformamide

MB:

Methylene blue

PBS:

Phosphate-buffered saline

Polox:

Poloxamer 407

PS:

Photosensitizer

PT:

Photodynamic therapy

TPA:

Texture Profile Analysis

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Acknowledgments and Disclosures

The authors acknowledge the Brazilian funding agencies CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), and FINEP (Financiadora de Estudos e Projetos) for their financial support and State University of Maringá for supporting the project.

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Authors and Affiliations

  1. Department of Pharmacy, Laboratory of Research and Development of Drug Delivery Systems, State University of Maringá, Colombo Avenue, 5790, K80, S22, CEP 87020-900, Maringá, PR, Brazil

    Fernanda Belincanta Borghi-Pangoni, Mariana Volpato Junqueira, Sabrina Barbosa de Souza Ferreira, Larissa Lachi Silva, Andrea Diniz & Marcos Luciano Bruschi

  2. Department of Chemistry, State University of Maringá, Colombo Avenue, 5790, Maringá, PR, Brazil

    Bruno Ribeiro Rabello & Wilker Caetano

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  1. Fernanda Belincanta Borghi-Pangoni
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  2. Mariana Volpato Junqueira
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  3. Sabrina Barbosa de Souza Ferreira
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  4. Larissa Lachi Silva
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  5. Bruno Ribeiro Rabello
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  7. Andrea Diniz
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  8. Marcos Luciano Bruschi
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Correspondence to Marcos Luciano Bruschi.

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Borghi-Pangoni, F.B., Junqueira, M.V., de Souza Ferreira, S.B. et al. Screening and In Vitro Evaluation of Mucoadhesive Thermoresponsive System Containing Methylene Blue for Local Photodynamic Therapy of Colorectal Cancer. Pharm Res 33, 776–791 (2016). https://doi.org/10.1007/s11095-015-1826-8

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  • DOI: https://doi.org/10.1007/s11095-015-1826-8

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