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Mucoadhesive Films of Docetaxel with Ceramide as an Adjuvant Monitoring Polymer-Drug Partitioning for Optimal Drug Release

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Abstract

Background

Millions of individuals worldwide are affected by cancer, with increasing instances by 1% annually and strikingly high mortality rates of 0.4% per year for cancers of the oral cavity and 2% for cancers of the tongue, tonsil, and oropharynx. Here we propose the administration of the water-insoluble anti-cancer drug docetaxel (DTX) along with an adjuvant C6 ceramide (Cer) through the buccal route to overcome the challenges such as the wet site of administration and inadequate availability of the drug on-site, by increasing the residence time of the mucoadhesive film through the selection of polymers.

Materials and Method

Mucoadhesive films were prepared by solvent casting method. Using chitosan, HPMC K4M, HEC, and PVA homo- and heteroblended films (P1–P8) were prepared and optimized for the selection of suitable polymer composition. As a pre-formulation investigation, drug-excipient compatibilities (DSC and ATR-FTIR) were carried out. The DSC and ATR-FTIR investigation showed that the drug and the polymers had excellent compatibility. The films prepared were characterized for their percentage swelling index, residence time, physical appearance, weight, thickness, surface pH, folding endurance FE, percentage moisture absorption PMa, surface morphology SEM, drug content uniformity, in vitro drug release, and in vitro MTT assay. Results.

On the basis of the results of percentage swelling index, residence time, and dissolution data modelling applied using DD solver excel Add-in, from homo- and heteroblends of polymers scrutinized, chitosan, HEC, and PVA were selected for the choice of polymers as docetaxel showed non-Fickian diffusional release from the erodible polymeric film. Chitosan, HEC, and PVA were optimized using Box-Behnken design with the help of Design-Expert® software. Three independent variables were considered: amount of chitosan (A), amount of HEC (B), and PVA concentration (C). The percentage swelling index (R1: SI%) and residence time (min) (R2: RT) were selected as dependent variables or responses. CHeP10 with percentage swelling index 40.3 ± 1.15, residence time 326.66 ± 3.05 min, and 60.00 ± 0.734% drug released in 6 h was chosen for in vitro cell line studies against the CaL-27 cell line, where DTX-Cer-loaded CHeP10 showed a 15-time reduction of IC50 of plain DTX from 1.743 to 0.1108 nM. On the basis of these studies, we may conclude that the current approach comprising polymeric films can be successfully used for the local and enhanced anti-cancer activity of docetaxel for oral cancer.

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Data Availability

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.

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Acknowledgements

I would like to thank Professor Arnab Pal, Dr. Parul Kamboj, and Rajandeep Kaur from the Department of Biochemistry, PGIMER Chandigarh for in vitro cell line studies.

Funding

This study was supported by the Indian Council of Medical Research (ICMR), New Delhi, India (Grant Number: For Poornima Agrawal- 45/26/2020- Nan/BMS, dated January 22, 2021.

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  1. Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar, MP 470004, India

    Poornima Agrawal & Vandana Soni

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  1. Poornima Agrawal
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Contributions

Poornima Agrawal and Vandana Soni conceptualized the preliminary draft for the manuscript. Poornima Agrawal performed the studies and contributed in interpretation of results and writing of manuscript. Vandana Soni analyzed the entire work and made critical revisions and approved the final version of the paper. All authors reviewed and approved the final manuscript.

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Correspondence to Vandana Soni.

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Agrawal, P., Soni, V. Mucoadhesive Films of Docetaxel with Ceramide as an Adjuvant Monitoring Polymer-Drug Partitioning for Optimal Drug Release. J Pharm Innov 18, 1515–1532 (2023). https://doi.org/10.1007/s12247-023-09739-0

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