Abstract
Specific delivery to tumors and efficient cellular uptake of nucleic acids are major challenges for gene-targeted cancer therapies. Tumor-targeted delivery using antibody fragments or immunoliposomes have already been demonstrated to enhance cellular uptake of nucleic acids by receptor-mediated endocytosis. Here we report the first use of an epithelial cell adhesion molecule (EpCAM)-specific designed ankyrin repeat protein (DARPin) as a carrier for siRNA. Designed ankyrin repeat proteins are a novel class of non-immunoglobulin binding proteins relying on the modularity of ankyrins. Their short length, high stability, and the lack of intramolecular cysteines facilitate proper folding, result in high-yield expression in E. coli, and allow engineering procedures usually not well tolerated by antibodies. A DARPin binding to EpCAM was derived from a designed protein library using ribosome display.
Highlights
Extemporaneous compounding of drugs for children is used in order to meet the need for drug formulations and doses suitable for children
Oral suspensions and solutions may be an alternative to solid oral dosage forms and if no commercial liquid formulation is available, these can be manufactured extemporaneously
The aim of the study was to optimize the composition of two pediatric extemporaneous liquid preparations containing naloxone and propranolol by substituting paraben as a microbiological preservative and ethanol as a solubilizer, with excipients more suitable for pediatric use
Summary
Extemporaneous compounding of drugs for children is used in order to meet the need for drug formulations and doses suitable for children. Many drugs are administered orally and only available as solid oral dosage forms, mainly tablets. These may be unsuitable for children due to lack of appropriate doses and swallowing difficulties among young children. It may be difficult to divide a commercially available solid dosage form in a correct and reproducible manner when administering the medicine to children [2,3,4]. There is a need for suitable pediatric formulations to improve drug treatment of children [7,8,9,10,11,12]. Oral suspensions and solutions may be an alternative to solid oral dosage forms and if no commercial liquid formulation is available, these can be manufactured extemporaneously
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