فهرست نشریات علمی دسترسی آزاد ایران

The objective of the study was to design and test an ultrasound needle-free pediatrically compatible chemotherapy delivery system by combining nanocrystals technology with orally disintegrable films (ODFs) to enhance the solubility, bioactivity, and compliance of the drugs. The antisolvent precipitation technique was used to prepare the poorly water-soluble BCS Class II anticancer drug docetaxel in form of nanocrystals followed by the incorporation into polymeric ODF matrices. Design of Experiments (DoE) was used to optimize four formulations where the polymer type (HPMC and PVA), glycerol concentration used, and crosslinking conditions were taken into account. The physicochemical characteristics consisted of a particle size study, polydispersity index (PDI), disintegration time, and stability experiments were carried out in ICH accelerated (40 o C/75% RH) and long-term (25 o C/60% RH) storage conditions. The THP-1 leukemia and SH- SY5Y neuroblastoma cell lines were used to determine in vitro cytotoxicity. The best nanocrystals were optimized to provide a mean particle size of 245 +/- 18 nm with a PDI of 0.34, which is very uniform. All ODF solutions showed fast disintegration in 30 seconds, which fulfilled the pediatric administration criteria. Stability examinations indicated that the drug had great physicochemical stability with the retention being 98.3% at six months. Cytotoxicity tests indicated that the nanocrystal-loaded ODF had a much greater anticancer activity (IC 5 0 = 0.85 ) than free docetaxel and nanocrystal suspensions. This research paper has shown that nanocrystal-loaded orally disintegrating films are a promising needle-free, hospital compatible chemotherapy platform in the pediatric oncology. The formulation provides better drug efficacy, high stability, high disintegration rate, and better patient compliance, which have significant therapeutic and regulatory benefits in the treatment of cancer in children.