Self-Assembled Delivery Vehicles for Poorly Water-Soluble Drugs: Basic Theoretical Considerations and Modeling Concepts

Poor solubility is a well-recognized property of many drug molecules [1]. Unprotected administration of poorly water-soluble drugs is problematic. Aggregation, precipitation, uncontrolled binding, and direct exposure to a harsh biological environment render this process inefficient. The putative ‘solution’ of using higher drug concentrations narrows the window between a therapeutic success and unwanted side effects such as locally toxic drug levels. It comes as no surprise that the administration of poorly water-soluble drugs can benefit dramatically from using delivery vehicles. Such vehicles can, in principle, be designed not only to encapsulate a drug and protect it from biological defense mechanisms, but also to release the drug in a controlled manner at the target site and then to be recycled through biodegradation. Different types of delivery vehicles are currently being investigated, including microemulsions [2,3], gels [4], micelles [5,6], liposomes [7], polymersomes [8], dendrimers [9], and nanopcrystals [10], or lipid nanoparticles [11]. Notably, most of these are self-assembled structures. Self-assembly is an ubiquitous process in cellular systems, most strikingly perhaps in the cell membrane where a matrix (lipids) contains highly specialized functional units (poorly water-soluble proteins). Functionalization is an advantage that is also increasingly integrated into drug delivery vehicles. As an example