Thermosensitive and mucoadhesive sol-gel composites of paclitaxel/dimethyl-β-cyclodextrin for buccal delivery

• Published in: PloS one Vol. 9; no. 9; p. e109090
• Main Authors: Choi, Soon Gil, Lee, Sang-Eun, Kang, Bong-Seok, Ng, Choon Lian, Davaa, Enkhzaya, Park, Jeong-Sook
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.10.2014; Public Library of Science (PLoS)
• Subjects: Addition polymerization; Adhesiveness; Administration, Buccal; Anticancer properties; Aqueous solutions; beta-Cyclodextrins - chemistry; Breast cancer; Buffers; Calorimetry; Calorimetry, Differential Scanning; Cancer; Cell Death - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Cyclodextrin; Cyclodextrins; Cytotoxicity; Differential scanning calorimetry; Distilled water; Drug Delivery Systems; Drug dosages; Electron microscopy; Fourier transforms; Humans; Hydrogels; Hydrogels - chemistry; Inclusion complexes; Infrared spectrophotometers; Lung cancer; Lung diseases; Medicine and Health Sciences; Methyl-β-Cyclodextrin; Microscopy, Electron, Scanning; Oral cancer; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - pharmacology; Pharmacy; Phase Transition; Physical Sciences; Poloxamer - chemistry; Poloxamers; Polyethylene; Polyethylene Glycols - chemistry; Polyethylene oxide; Polyethylenes; Polymers; Potassium; Scanning electron microscopy; Skin; Sol-gel processes; Solubility; Solutions; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Temperature; Thermosensitive; Toxicity; Transition temperature; Transition temperatures; X-Ray Diffraction; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0109090

The purpose of this study was to develop a buccal paclitaxel delivery system using the thermosensitive polymer Pluronic F127 (PF127) and the mucoadhesive polymer polyethylene oxide (PEO). The anticancer agent paclitaxel is usually used to treat ovarian, breast, and non-small-cell lung cancer. To improve its aqueous solubility, paclitaxel was incorporated into an inclusion complex with (2,6-di-O-methyl)-β-cyclodextrin (DMβCD). The formation of the paclitaxel inclusion complex was evaluated using various techniques, including x-ray diffractometry (XRD), Fourier-transform infrared (FT-IR) spectrophotometry, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Hydrogels were prepared using a cold method. Concentrations of 18, 20, and 23% (w/v) PF127 were dissolved in distilled water including paclitaxel and stored overnight in a refrigerator at 4 °C. PEO was added at concentrations of 0.1, 0.2, 0.4, 0.8, and 1% (w/v). Each formulation included paclitaxel (0.5 mg/mL). The sol-gel transition temperature of the hydrogels was measured using the tube-inverting method. Drug release from the hydrogels was measured using a Franz diffusion cell containing pH 7.4 phosphate-buffered solution (PBS) buffer at 37 °C. The cytotoxicity of each formulation was measured using the MTT assay with a human oral cancer cell (KB cell). The sol-gel transition temperature of the hydrogel decreased when PF127 was present and varied according to the presence of mucoadhesive polymers. The in vitro release was sustained and the release rate was slowed by the addition of the mucoadhesive polymer. The cytotoxicity of the blank formulation was low, although the drug-loaded hydrogel showed acceptable cytotoxicity. The results of our study suggest that the combination of a PF 127-based mucoadhesive hydrogel formulation and inclusion complexes improves the in vitro release and cytotoxic effect of paclitaxel.