Stabilization of Glycoprotein Liquid Formulation Using Arginine: A Study with Lactoferrin as a Model Protein

Abstract

The formulation of new biotherapeutics without human serum albumin (HSA) could decrease the potential risk of blood-transmitted diseases and those caused by infectious viruses and other pathogens. In the present study, arginine was examined as a potential alternative to HAS, and bovine lactoferrin (bLf) was used as a representative model glycoprotein since bLf has potential immunomodulatory and antiviral activity. The optimal formulation for the mixture was determined to be 10 mM arginine, 15% (w/v) trehalose, and 0.02% (v/v) Tween 80, using a statistical analysis program, Minitab. Analyses were performed using reverse-phase high-performance liquid chromatography (HPLC) and SDS-PAGE. The blf HSA-free formulations lost only 12-20% of blf compared with 46% for control (without additives) after 28 d of storage. Based on long-term stability studies, the HSA-free formulation developed in this study had a stronger effect on the stability of bLf (1.4-fold) than HSA formulation under various storage conditions over 6 months.

Formulation and Stability of Cytokine Therapeutics

“…The surfactant reduces adsorption and aggregation propensity, similar to the role played by albumin in the previous formulation. Arginine is a basic amino acid that can be used to preserve protein activity, especially when alternatives to the use of serum albumin are sought . Its importance as a protein formulation excipient is rapidly growing .…”

Probing of l-Arginine as an Additive for the Temperature-Induced Aggregation of Veterinary Growth Hormones: Fluorescence Study

“…L-arginine is widely used in the refolding process of recombinant proteins for the aggregation suppression [5,6]. However, the application of L-arginine as an antiaggregatory agent in their formulations is not widespread and fully investigated with the exception of a few proteins mentioned above [4,[7][8][9]. We show that L-arginine suppresses the heat-induced aggregation of mink and pGHs and has no influence on their structure.…”

“…Recently, the effects of arginine on the stability of fibroblast growth hormone factor 20 and IgG1 monoclonal antibodies have been studied to probe this amino acid as a potential additive for their formulation development [7,8]. A novel liquid formulation using arginine as a stabilizing agent was also developed for glycoprotein lactoferrin [9]. The interaction of arginine with proteins differs from other amino acids.…”

Impact of Gemini Surfactants on the Stability of Insulin using Computational Tools

“…hydrophobic interaction. Different modifications in the structure of insulin have been made to affect insulin [9][10][11][12][13][14][15][16][17][18][19][20][21]. Insulin has the tendency to undergo for the structural transformation and results in aggregation and formation of insoluble insulin fibrils.…”

“…Therefore, most popular methods for the stabilization of the insulin against fibrillation contribute to counteract associated insulin from being disassembled [2, [9][10][11][12][13]22]. It is evident that the stabilization mechanism is consistent with the destabilising role attributed to hydrophobic surfaces [14][15][16][17][18][19][20][21][22][23][24][25][26].…”