title: Exploring the effect of hydrophilic and hydrophobic structure of grafted polymeric micelles on drug loading.
abstract: The objective of this paper is to explore the effect of hydrophilic and hydrophobic structure of grafted polymeric micelles on drug loading, and elucidate whether drug-polymer compatibility, as predicted by Hansen solubility parameters (HSPs), can be used as a tool for drug-polymer pairs screening and guide the design of grafted polymeric micelles. HSPs of 27 drugs and three grafted copolymers were calculated according to group contribution method. The drug-polymer compatibilities were evaluated using the approaches of Flory-Huggins interaction parameters (χFH) and polarity difference (△Xp). Two models, model A and B, were put forward for drug-polymer compatibility prediction. In model A, hydrophilic/hydrophobic part as a whole was regarded as one segment. And, in model B, hydrophilic and hydrophobic segments were evaluated individually. First of all, using chitosan (CS)-grafted-glyceryl monooeate (GMO) based micelle as an example, the suitability of model A and model B for predicating drug-polymer compatibility was evaluated theoretically. Thereafter, corresponding experiments were carried out to check the validity of the theoretical prediction. It was demonstrated that Model B, which evaluates drug compatibility with both hydrophilic and hydrophobic segments of the copolymer, is more reliable for drug-polymer compatibility prediction. Moreover, the approach of model B allows for the selection of a defined grafted polymer with for a specific drug and vice versa. Thus, drug compatibility evaluation via HSPs with both hydrophilic and hydrophobic segments is a suitable tool for the rational design of grafted polymeric micelles. The molecular dynamics (MD) simulation study provided further support to the established model and experimental results.
authors: School of Pharmacy, Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Chenjun
authors: C
authors: Shi
authors: School of Pharmacy, Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Yujiao
authors: Y
authors: Sun
authors: School of Pharmacy, Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Haiyang
authors: H
authors: Wu
authors: School of Pharmacy, Department of Physical Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Chengyun
authors: C
authors: Zhu
authors: School of Pharmacy, Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Guoguang
authors: G
authors: Wei
authors: School of Pharmacy, Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Jinfeng
authors: J
authors: Li
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences (ICMS), University of Macau, Macau, China.
authors: Tenglan
authors: T
authors: Chan
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences (ICMS), University of Macau, Macau, China.
authors: Defang
authors: D
authors: Ouyang
authors: School of Pharmacy, Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: maoshirui@syphu.edu.cn.
authors: Shirui
authors: S
authors: Mao
mesh_terms: D048271:Chitosan / Q000737:chemistry; D004344:Drug Incompatibility; D005989:Glycerides / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D008962:Models, Theoretical; D056004:Molecular Dynamics Simulation; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D005989:Glycerides; D008823:Micelles; D004364:Pharmaceutical Preparations; D011108:Polymers; D048271:Chitosan; C005953:monoolein
keywords: Drug-polymer compatibility; Flory-Huggins interaction parameter; Grafted polymeric micelles; Hansen solubility parameter