Study of Self-Assembly of Cyclodextrin Conjugates with Phospholipid by Molecular Dynamics Method

Targeted delivery of hydrophobic drugs is an urgent problem in pharmaceutics. These drugs are poorly soluble in water, which makes it difficult to transport them in the body and requires an increase in dosage, which can lead to side effects. Cyclodextrins can help solve this problem owing to their unique hydrophobic cavity, into which the drug can be embedded, and the hydrophilic outer surface, which ensures the solubility of such a complex in water. Lipid derivatives of cyclodextrins in an aqueous medium, owing to the hydrophobic interactions of lipid fragments, form micelle-like nanoparticles that are also soluble in water and capable of embedding hydrophobic molecules. Thus, the use of lipid derivatives of cyclodextrins in the process of creation of nanoparticles can improve the bioavailability and pharmacokinetic properties of drugs. In this study, the self-assembly of phospholipid conjugates with α-, β- and γ-cyclodextrins into nanoparticles is simulated by using the method of molecular dynamics produced using the GROMACS software package. As a result of calculations, models of micelle nanoparticles in the coarse-grained representation were obtained, the conformation of molecules in their composition was established, and the size of micelles was determined.