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

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((R)) 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.

Automated summary

This study proposes the buccal administration of the water-insoluble anti-cancer drug docetaxel (DTX) with an adjuvant C6 ceramide (Cer) to overcome the challenges of wet site of administration and inadequate drug availability on-site, by increasing the residence time of mucoadhesive film. Mucoadhesive films were prepared and chitosan, HEC, and PVA were selected as suitable polymers based on the percentage swelling index, residence time, and dissolution data modelling. CHeP10 with optimized polymer composition showed enhanced anti-cancer activity against oral cancer in vitro.