Self-Assembly Drugs: From Micelles to Nanomedicine

Abstract

Self-assembly has fascinated many scientists over the past few decades. Rapid advances and widespread interest in the study of this subject has led to the synthesis of an ever-increasing number of elegant and intricate functional structures with sizes that approach nano-and mesoscopic dimensions. Today, it has grown into a mature field of modern science whose interfaces with many disciplines have provided invaluable opportunities for crossing boundaries for scientists seeking to design novel molecular materials exhibiting unusual properties, and for researchers investigating the structure and function of biomolecules. Consequently, self-assembly transcends the traditional divisional boundaries of science and represents a highly interdisciplinary field including nanotechnology and nanomedicine. Basically, self-assembly focuses on a wide range of discrete molecules or molecular assemblies and uses physical transformations to achieve its goals. In this Review, we present a comprehensive overview of the advances in the field of drug self-assembly and discuss in detail the synthesis, self-assembly behavior, and physical properties as well as applications. We refer the reader to past reviews dealing with colloidal molecules and colloidal self-assembly. In the first part, we will discuss, compare, and link the various bioinformatic procedures: Molecular Dynamics and Quantitative Structure Activity Relationship. The second section deals with the self-assembly behavior in more detail, in which we focus on several experimental techniques, selected according to the depth of knowledge obtained. The last part will review the advances in drug-protein assembly. Nature provides many examples of proteins that form their substrate binding sites by bringing together the component pieces in a process of self-assembly. We will focus in the understanding of physical properties and applications developing thereof.

Solubilization Behavior of Polyene Antibiotics in Nanomicellar System: Insights from Molecular Dynamics Simulation of the Amphotericin B and Nystatin Interactions with Polysorbate 80

“…Aggregation of hydrophobic molecules in the aqueous media is known to be driven by unfavorable contacts between water and their hydrophobic domains [1,3,84]. It has been shown that as the self-association proceeds, the solvent accessible surface area (SASA) of the hydrophobic solute is constantly limited in a linear correlation with the unfavorable contacts [46,84,85].…”

“…The therapeutic index (TI) of many surface active drugs is limited due to their tendency to self-associate in aqueous medium, resulting in low solubility, limited bioavailability, and potential severe side effects of these pharmaceuticals [1,2]. The clinical advantages of overcoming this challenge have provoked a large body of research into the development of formulations with improved pharmaceutical properties [3]. Among the most surface active drugs with an extending therapeutic use is the Amphotericin B (AmB).…”

<strong>3D hierarchically scaffolds for bone repair: at the crossroads of experimental and computational outlooks</strong>

“…One of the main goals of nanomedicine is to develop new biocompatible scaffolds [3]. These materials in order to perform effectively must have an appreciation of the complex interrelationships between humans and the physical/chemical components of the environment [4].…”

Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions

“…(b) Hydrophobic drugs such as steroids do also self-assemble in aqueous solutions to form dimers, trimers, and higher order oligomers to reduce their contact surface with water. 11 describing the critical micelle concentration (CMC) are highlighted in a publication by Messina et al 19 Frequently, the main descriptors depend on the size and surface area of the hydrophobic and hydrophilic moieties as well as on numerous other molecular properties such as the structural complexity of the hydrophobic moiety, van der Waals volume of the molecule, molecular flexibility, dipole moment of the molecule, relative positive charge and partial positive surface area of the hydrophobic domain, heat of formation, and the octanol-water partition coefficient. For example, increased chain length of a hydrophobic moiety usually decreases the CMC value.…”

“…Regarding external factors, increase of medium ionic strength will reduce solute hydration, decrease electrostatic repulsion, and increase counterion binding that ultimately will decrease the CMC. 19,24 Changing of ionic strength is more effective for ionic substances than nonionic ones. Influence of temperature on aggregation process is, however, not so ambiguous.…”