ABSTRACT
The discovery of microRNAs (miRNAs) in 1993 has challenged the dogma of gene expression regulation. MiRNAs affect most of cellular processes from metabolism, through cell proliferation and differentiation, to cell death. In cancer, deregulated miRNA expression leads to tumor development and progression by promoting acquisition of cancer hallmark traits. The multi-target action of miRNAs, which enable regulation of entire signaling networks, makes them attractive tools for the development of anti-cancer therapies. Hence, supplementing downregulated miRNA by synthetic oligonucleotides or silencing overexpressed miRNAs through artificial antagonists became a common strategy in cancer research. However, the ultimate success of miRNA therapeutics will depend on solving pharmacokinetic and targeted delivery issues. The development of a number of nanocarrier-based platforms holds significant promises to enhance the cell specific controlled delivery and safety profile of miRNA-based therapies. In this review, we provide among the most comprehensive assessments to date of promising nanomedicine platforms that have been tested preclinically, pertaining to the treatment of selected solid tumors including lung, liver, breast, and glioblastoma tumors as well as endocrine malignancies. The future challenges and potential applications in clinical oncology are discussed.
ABSTRACT
Terbutaline sulfate fast dissolving sublingual films were prepared using seven drug compatible film formers in different combinations and proportions. The film polymers are maltodextrin, Na alginate, Carpabol 430, xanthan gum, HPMC E5, PVP K-25, and Na CMC. Propylene glycol and sorbitol were used as plasticizers and mannitol as filler. The optimum polymer concentrations and the plasticizer amount were selected on the basis of flexibility, tensile strength, and stickiness of the films. The prepared films were evaluated for their tensile strength, thickness uniformity, disintegration time (in vitro and in vivo), in vitro dissolution, and moisture content. Polymer type rather than total polymer concentration or plasticizer amount showed a significant effect on the tested film properties. A randomized, single dose, crossover study was conducted in four healthy volunteers to compare the pharmacokinetic profile of terbutaline sulfate from the prepared films and the conventional oral tablets. The film formula of choice gave a significantly faster drug absorption rate and recorded a relative bioavailability of 204.08%. Sublingual films could be promising as a convenient delivery system for terbutaline sulfate in patients with swallowing problems. The improved extent of absorption (higher AUC(0-24)) indicates success in improving drug bioavailability, and the faster absorption rate could be promising for the management of acute episodes of asthma.
