Structural Analysis of Hyaluronic Acid Fillers Using Nuclear Magnetic Resonance: Implications for Quality Control and...

Area of Science:

• Biomaterials Science
• Analytical Chemistry
• Dermatology

Background:

• Hyaluronic acid (HA) fillers can have biocompatibility issues due to residual cross-linking agents like 1,4-butanediol diglycidyl ether (BDDE).
• Assessing the degree of modification (MoD) and cross-linker ratio (CrR) is vital for understanding HA filler quality and safety.

Purpose of the Study:

• To analyze commercially available HA fillers using nuclear magnetic resonance (NMR).
• To evaluate key parameters including MoD, CrR, and the degree of cross-linking.
• To investigate the relationship between MoD and CrR in HA fillers.

Main Methods:

• Thirteen commercial HA filler samples were analyzed using NMR spectroscopy.
• Each sample underwent a 26-hour analysis for MoD and CrR determination.
• Specific NMR techniques were employed to quantify MoD (¹H and ¹³C) and CrR (¹³C).

Main Results:

• MoD ¹H values ranged from 2.239% to 17.065%, and MoD ¹³C values ranged from 1.947% to 12.567%.
• CrR ¹³C values varied from 0.014 to 0.394.
• Significant differences in CrR ¹³C were observed even when MoD values were similar, highlighting complex cross-linking variations.

Conclusions:

• Considering both MoD and CrR is essential for optimizing HA filler cross-linking and minimizing risks from residual BDDE.
• NMR is a valuable tool for HA gel characterization, aiding quality control, safety assessment, and clinical performance evaluation.
• Further research correlating NMR findings with clinical outcomes is necessary to ensure HA filler safety and efficacy.