title: Interfacial molecular interactions based on the conformation recognition between the insoluble antitumor drug AD-1 and DSPC.
abstract: In this study, molecular interactions between the anti-cancer agent 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol (AD-1) and phospholipid 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) were investigated using the Langmuir film balance technique. The characteristics of binary Langmuir monolayers consisting of DSPC and AD-1 were conducted on the basis of the surface pressure-area per molecule (π-A) isotherms. It was found that the drug was able to become efficiently inserted into preformed DSPC monolayers, indicating a preferential interaction between AD-1 and DSPC. For the examined lateral pressure at 20mN/m, the largest negative values of ΔGex were found for the AD-1/DSPC monolayer, which should be the most stable. Based on the calculated values of ΔGex, we found that the AD-1/DSPC systems exhibited the best mixed characteristics when the molar fraction of the AD-1 was 0.8; at that relative concentration, the AD-1 molecules can mix better and interact with the phospholipid molecules. In addition, the drug-DSPC binary supramolecular structure was also deposited on the mica plates as shown by atomic force microscopy (AFM). Finally, molecular docking calculations explained satisfactorily that, based on the conformations interactions (conformation recognition), even at an AD-1/DSPC molar ratio as high as 8:2, the interfacial stabilization of the AD-1/DSPC system was fairly strong due to hydrophobic interactions. A higher loading capacity of DSPC might be possible, as it is associated with a more flexible geometrical environment, which allows these supramolecular structures to accept larger increases in drug loading upon steric binding.
authors.affiliation: School of Functional food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China; School of Chinese Materia Media, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yin
authors.affiliation: School of Chinese Materia Media, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Xiuxiu
authors.initials: X
authors.lastname: Cao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Structure-based Drug Design and Discovery, Shenyang Pharmaceutical University, ministry of Education, Shenyang 110016, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Functional food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Su
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Gou
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Haibing
authors.initials: H
authors.lastname: He
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Guo
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: tanglab@126.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
authors.affiliation: School of Functional food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: zyq4885@126.com.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D008567:Membranes, Artificial; D018625:Microscopy, Atomic Force; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D013499:Surface Properties; D014315:Triterpenes / Q000737:chemistry* / Q000378:metabolism; D000097669:Dammaranes
chemical_list: D000970:Antineoplastic Agents; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D014315:Triterpenes; C517965:25-methoxydammarane-3,12,20-triol; D000097669:Dammaranes; C010942:1,2-distearoyllecithin
keywords: 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC); 12β; 20(R)-25-methoxyl-dammarane-3β; 20-triol (AD-1); Conformation recognition; High drug loading capacity; Langmuir monolayer; Molecular interactions