3 years ago

Gaining Insights into Specific Drug Formulation Additives for Solubilizing a Potential Anti-Alzheimer Disease Drug B4A1

Gaining Insights into Specific Drug Formulation Additives for Solubilizing a Potential Anti-Alzheimer Disease Drug B4A1
Katharina Linkert, Anna Grafl, Hans G. Börner, Carmen Lawatscheck, Marcus Pickhardt, Eckhard Mandelkow, Frank Polster
The pharmacological profiles of small molecule drugs are often challenged by their poor water solubility. Sequence-defined peptides attached to poly(ethylene glycol) (PEG) offer opportunities to overcome these difficulties by acting as drug-specific formulation additives. The peptide-PEG conjugates enable specific, noncovalent drug binding via tailored peptide/drug interactions as well as provide water solubility and drug shielding by well-solvated PEG-blocks. A systematic set of specific solubilizers for B4A1 as a potential anti-Alzheimer disease drug is synthesized and variations involve the length of the PEG-blocks as well as the sequences of the peptidic drug-binding domain. The solubilizer/B4A1 complexes are studied in order to understand contributions of both PEG and peptide segments on drug payload capacities, drug/carrier aggregate sizes, and influences on inhibition of the Tau-protein aggregation in an in vitro assay. Peptid-poly(ethylene glycol) (PEG) conjugates can be used as effective and selective solubilizers for the experimental anti-Alzheimer drug B4A1, exhibiting high potentials but poor water solubility. Selectivity of the peptide sequences and variation of the size of the PEG-block affect the payload and impact drug activity as shown in in vitro ThioflavinS TAU protein aggregation assays.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mabi.201700109

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