TY - JOUR
T1 - Investigating triazine-based modification of hyaluronan using statistical designs
AU - Liang, Jue
AU - Cheng, Lulu
AU - Struckhoff, Jessica J.
AU - Ravi, Nathan
N1 - Funding Information:
This research was supported by a NIH Core Grant P30 EY02687 and an NIH grant, EY021620 to Dr. Nathan Ravi. Also, Research to Prevent Blindness , Inc., and Department of Veterans Affairs Rehab Merit Review grant RX000657-01 provided support. We thank Paul David Hamilton for consultation and technical assistance. We acknowledge the use of Design-Expert® software, version 7, Stat-Ease, Inc., Minneapolis, MN, USA, www.statease.com , for our statistical analysis.
Publisher Copyright:
© 2015 Published by Elsevier Ltd.
PY - 2015/7/9
Y1 - 2015/7/9
N2 - Abstract Hyaluronan (HA) and its derivatives have been extensively researched for many biomedical applications. To precisely tailor the property of HA by derivatizing it to a pre-determined extent is challenging, yet critical. In this paper, we used 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methylmorpholine (NMM) to derivatize HA via a triazine-based coupling reaction. Using a fractional factorial (FF) design, we observed that water content in the solvent, and molar ratios of CDMT and NaHCO3 to the carboxylate were the significant factors controlling the derivatization. We investigated how the effect of each factor changes as reaction conditions change. Moreover, by altering the amount of CDMT and NaHCO3, we developed a cubic regression model for precise control of the extent of derivatization using a response surface methodology (RSM) with a D-optimal design. No spurious peaks were detected by 1H NMR spectrum and only 10% decrease of molecular weight of the derivatized HA was determined by GPC. The HA with 6% modification was relatively biocompatible up to 15 mg/mL.
AB - Abstract Hyaluronan (HA) and its derivatives have been extensively researched for many biomedical applications. To precisely tailor the property of HA by derivatizing it to a pre-determined extent is challenging, yet critical. In this paper, we used 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methylmorpholine (NMM) to derivatize HA via a triazine-based coupling reaction. Using a fractional factorial (FF) design, we observed that water content in the solvent, and molar ratios of CDMT and NaHCO3 to the carboxylate were the significant factors controlling the derivatization. We investigated how the effect of each factor changes as reaction conditions change. Moreover, by altering the amount of CDMT and NaHCO3, we developed a cubic regression model for precise control of the extent of derivatization using a response surface methodology (RSM) with a D-optimal design. No spurious peaks were detected by 1H NMR spectrum and only 10% decrease of molecular weight of the derivatized HA was determined by GPC. The HA with 6% modification was relatively biocompatible up to 15 mg/mL.
KW - Amidation
KW - Fractional-factorial design
KW - Hyaluronan
KW - Response surface methodology
KW - Triazine Coupling
UR - http://www.scopus.com/inward/record.url?scp=84936744405&partnerID=8YFLogxK
U2 - 10.1016/j.carbpol.2015.06.067
DO - 10.1016/j.carbpol.2015.06.067
M3 - Article
C2 - 26256372
AN - SCOPUS:84936744405
SN - 0144-8617
VL - 132
SP - 472
EP - 480
JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
M1 - 10058
ER -