Designing micellar nanocarriers with improved drug loading and stability based on solubility parameter.
The objective of this study is to demonstrate the feasibility of using solubility parameter as guidance for the design and identification of a stable micellar system with a high drug loading capacity for oral drug delivery. Using hydroxycamptothecin (HCPT) as a model drug, the effect of three hydrophobic blocks (fatty glycerides) grafted onto chitosan on the drug loading and stability of HCPT-loaded micellar nanoparticles formed by pH precipitation method were studied systematically. The Flory-Huggins interaction parameter (χFH) calculated by the group contribution method (GCM) and molecular dynamics simulation (MDS) was used to assess the compatibility between HCPT and the copolymers. The predicted order of compatibility between three chitosan derivatives and HCPT was verified experimentally. A high drug loading and remarkably stable micellar system for oral administration based on succinylated glycerol monooleate-chitosan was discovered in this study. Our study suggests that the miscibility between drug and copolymer is crucial to drug loading and stability of the micellar system. Thus, the calculation of χFH using GCM and MDS methods is useful for guiding the design or screening of a suitable copolymer for preparing drug-loaded micellar nanocarrier systems.
['Tian|Ye|Y|', 'Shi|Chenjun|C|', 'Sun|Yujiao|Y|', 'Zhu|Chengyun|C|', 'Sun|Changquan Calvin|CC|', 'Mao|Shirui|S|']
D001702:Biopharmaceutics D002166:Camptothecin D048271:Chitosan D016503:Drug Delivery Systems D004355:Drug Stability D006801:Humans D066298:In Vitro Techniques D008823:Micelles D046529:Microscopy, Electron, Transmission D008958:Models, Molecular D056004:Molecular Dynamics Simulation D015394:Molecular Structure D053769:Nanocapsules D010316:Particle Size D012995:Solubility
micellar system group contribution method chitosan derivatives Flory−Huggins interaction parameter molecular simulation