Study of the effect of mixing approach on cross-linking efficiency of hyaluronic acid-based hydrogel cross-linked with 1,4-butanediol diglycidyl ether.
Regardless of various strategies reported for cross-linking hyaluronic acid (HA) with 1,4-butanediol diglycidyl ether (BDDE), seeking new strategies that enhance cross-linking efficiency with a low level of cross-linker is essential. In this work, we studied the influence of mixing approach on two cross-linked BDDE-HA hydrogels prepared by two different mixing approaches; the large-batch mixing approach in which the hydrogel quantities were all mixed as a single lump in one container (hydrogel 1), and the small-batches mixing approach in which the hydrogel quantities were divided into smaller batches, mixed separately at various HA/BDDE ratios then combined in one reaction mixture (hydrogel 2). The result showed that the cross-linking reaction was mixing process-dependent. Degradation tests proved that, in relation to hydrogel 1, hydrogel 2 was more stable, and exhibited a higher resistance towards hyaluronidase activity. The swelling ratio of hydrogel 1 was significantly higher than that of hydrogel 2 in distilled water; however, in phosphate buffer saline, both hydrogels showed no significant difference. SEM images demonstrated that hydrogel 2 composite showed a denser network structure and smaller pore-size than hydrogel 1. In comparison to native HA, the occurrence of chemical modification in the cross-linked hydrogels was confirmed by FTIR and NMR distinctive peaks. These peaks also provided evidence that hydrogel 2 exhibited a higher degree of modification than hydrogel 1. In conclusion, the small-batches mixing approach proved to be more effective than large-batch mixing in promoting HA-HA entanglement and increasing the probability of BDDE molecules for binding with HA chains.
Institute of Pharmacy, Department of Pharmaceutics and Biopharmaceutics, Martin-Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany.
Mohammed
M
Al-Sibani
Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, Birkat Al-Mouz, Nizwa 616, Oman.
Ahmed
A
Al-Harrasi
Institute of Pharmacy, Department of Pharmaceutics and Biopharmaceutics, Martin-Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany; Institute of Applied Dermatopharmacy, Martin-Luther University Halle-Wittenberg, Weinbergweg 23, 06120 Halle/Saale, Germany. Electronic address: reinhard.neubert@pharmazie.uni-halle.de.
Reinhard H H
RH
Neubert
D002072:Butylene Glycols / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D006820:Hyaluronic Acid / Q000737:chemistry*; D006821:Hyaluronoglucosaminidase / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D066244:Proton Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared
D002072:Butylene Glycols; D003432:Cross-Linking Reagents; D020100:Hydrogels; D006820:Hyaluronic Acid; C014376:1,4-bis(2,3-epoxypropoxy)butane; D006821:Hyaluronoglucosaminidase
Cross-linking efficiency; Degradation rate; Degree of modification; Hyaluronic acid; Swelling ratio