title: Designing micellar nanocarriers with improved drug loading and stability based on solubility parameter.
abstract: 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.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Chenjun
authors.initials: C
authors.lastname: Shi
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Sun
authors.forename: Chengyun
authors.initials: C
authors.lastname: Zhu
authors.forename: Changquan Calvin
authors.initials: CC
authors.lastname: Sun
authors.forename: Shirui
authors.initials: S
authors.lastname: Mao
mesh_terms: D001702:Biopharmaceutics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry; 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 / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D012995:Solubility
chemical_list: D008823:Micelles; D053769:Nanocapsules; C527042:hydroxycamptothecinum; D048271:Chitosan; D002166:Camptothecin
keywords: Flory−Huggins interaction parameter; chitosan derivatives; group contribution method; micellar system; molecular simulation