title: Bilateral Effects of Excipients on Protein Stability: Preferential Interaction Type of Excipient and Surface Aromatic Hydrophobicity of Protein.
abstract: OBJECTIVE
  Understanding the mechanism of protein-excipient interaction and illuminating the influencing factors on protein stability are key steps in the rational design of protein formulations. The objective of this study was to assess effects of preferential interaction type of excipient and surface aromatic hydrophobicity of protein on protein solution stability.
  
  
  METHODS
  The preferential interaction between excipient and aromatic hydrophobic area of protein was investigated by solubility and fluorescence studies of amino acid derivatives in excipient solutions. We examined conformational, colloidal and mechanical stabilities of model proteins with different surface aromatic hydrophobicities, including bovine serum albumin (BSA) and ovalbumin (OVA), and then stability data were visualized by three-index empirical phase diagram.
  
  
  RESULTS
  The result showed that preferentially excluded excipients (trehalose, sucrose and sorbitol) protected protein conformation against damage, but they could accelerate mechanical stress-induced aggregation. Preferentially bound excipients (propanediol and arginine) suppressed BSA aggregation, but arginine failed to inhibit OVA aggregation, which might be attributed to the disparate conformational perturbing effects of arginine on aromatic hydrophobic regions of BSA and OVA.
  
  
  CONCLUSIONS
  These findings provided strong evidence that excipient possessed bilateral effects, and its application should be determined on different preferential interaction behaviors of excipients with protein, especially with the aromatic hydrophobic region.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3 Southern Renmin Road, Chengdu, Sichuan Province, 610041, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wen
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3 Southern Renmin Road, Chengdu, Sichuan Province, 610041, People's Republic of China.
authors.forename: Xianxian
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3 Southern Renmin Road, Chengdu, Sichuan Province, 610041, People's Republic of China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3 Southern Renmin Road, Chengdu, Sichuan Province, 610041, People's Republic of China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Lan
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3 Southern Renmin Road, Chengdu, Sichuan Province, 610041, People's Republic of China. yzn@scu.edu.cn.
authors.forename: Zongning
authors.initials: Z
authors.lastname: Yin
mesh_terms: D001120:Arginine / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003102:Colloids; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D010047:Ovalbumin / Q000737:chemistry; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D011487:Protein Conformation; D055550:Protein Stability; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012995:Solubility; D012996:Solutions; D013012:Sorbitol / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry; D013499:Surface Properties; D014199:Trehalose / Q000737:chemistry; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D003102:Colloids; D005079:Excipients; C000626823:N-acetyl-L-phenylalanine amide; D011409:Propylene Glycols; D012996:Solutions; C019142:N-acetyltyrosylamide; C016952:N-acetyltryptophanamide; D012710:Serum Albumin, Bovine; D014443:Tyrosine; D010649:Phenylalanine; D013012:Sorbitol; D013395:Sucrose; D014364:Tryptophan; D010047:Ovalbumin; D001120:Arginine; D014199:Trehalose
keywords: Conformational change; excipient; preferential interaction; protein stability; surface aromatic hydrophobicity