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Surface Tension and Flow Properties of Hyaluronic Solutions Ing. Martin Chytil doc. Ing. Miloslav Pekař, CSc Brno University of Technology Faculty of Chemistry – Institute of Physical and Applied chemistry

1) What was the study about?

Hyaluronic acid (HA) - widely occurred polysaccharide Unique properties of HA predict its huge range of applications (pharmacy, cosmetics, medicine etc.) Hydrophobic modification of HA – change in some properties (hydrophilic/hydrophobic character)  possibility in solubilization and drug carrier delivery Research focused on rheological and surface active properties of these compounds in aq. solutions Studied compounds produced by

1) What was the study about?  Hyaluronic acid (HA); Mw:  183.9×10 3  HALW 0.56×10 6  HAHW 1.63× 10 6  HA derivates: hydrophobically modified HA by N-alkyl  Derivates with ether ( epoxy ) bond  Derivates with carbamate bond R – butyl, hexyl, octyl, decyl, dodecyl M r of derivates: cca kDa Studied compounds DerivatesSD [%]M r [-]× C 4 -Ep-HA C 6 -Ep-HA C 8 -Ep-HA C 10 -Ep-HA C 12 -Ep-HA489 Derivates- NH SD [%]M r [-]× C 4 – C

1) What was the study about? HA + () R1: C 4 –C 12 Shortened Scheme of HA Derivatives Synthesis

2) Experimental

 Samples for measurements:  Solutions of HA and HA derivates in 0.1 M phosphate buffer with NaCl (0.15 M); pH ~ 7  Rheology of samples studied material τ,γ˙, γ, n, M, ω loading deformation Response – resistence against deformation η, C, G Cone-Plate sensor

2) Experimental  Surface active properties and association ability studied by the surface tension measurements of the samples solutions at lab. temperature ( ca 75 °F; ca 23 °C)  Measurements performed using the Pt-ring method Demonstration of surface tension measurement; F represents force of the ring tearing off the liquid surface; R means ring radius

3) Results and discussions

Flow Behavior of HA and HA Derivates Various settings of measurements for C6-EP-HA (Mw ; SD 8.7%) Flow and viscosity curves of HA (Mw 1.63 ×10 6 ) aq. solution

3) Results and discussions Concentration, alkyl chain length and SD influences of HA derivatives concentration The influence of an alkyl chain length

3) Results and discussions The Surface Tension Measurement Results: Comparison of the HA Derivates with SDS SD ( OK-NH-HA7) = 18.82%; γ s represents surface tension of a sample, γ – surface tension of buffer, w – weight concentration in % w/w. Comparison of the surface activity of the OK-NH-HA7 with HA LW CMC formation of a gel

3) Results and discussions The surface Tension Measurement Results: The Alkyl Chain Length and SD Influences The alkyl chain length influence for the epoxy HA derivates

4) Conclusions  The poorer rehological behavior of HA derivates in aq. solutions in comparison to HA  The hexyl derivates displayed the most advantageous rheological behavior  A HA derivate could be built into HA gel/solution and solubilize poorly soluble ( ophthalmic) drugs  The most convenient derivates for solubilization: hexyl, and octyl even with the middle low SD (ca 30%) and octyl carbamate derivates with the highest SD