Сборник V международной

MODIFIED HYALURONIC ACID BASED HYDROGELS FOR THE SUSTAINED
DELIVERY OF DOXORUBICIN
Boydedayev A.A.1, Muhitdinov B.I.1, Turaev A.S.1, Huang Y.2, Amonova D.M.1,
Wang H.2, Qirg’izbayev.H.H.1
1 Institute o f Bioorganic Chemistry, Uzbekistan Academy o f Sciences, 
2Shanghai Institute ofM ateria Medica, Chinese Academy o f Sciences, 501 Hai Ke Road, 201203
Shanghai, China
e-mail: [e-mail], tel. [phone]
Over the last decade, efforts for the preparation and biological inspection of injectable hydrogels 
have been increased since these types o f materials have many advantages regarding their local applicability 
and improved therapeutic effects. In this context, biopolymers have been frequently used for local delivery 
and to increase the efficiency of various therapeutic materials. In addition, the biopolymers are considered 
appropriate matrixes for the hydrogels due to their multifunctional chemical structure, biodegradability, 
biocompatibility, and non-toxic properties. Moreover, some biopolymers can dramatically improve the 
therapeutic effect of the drug payloads by specifically binding with cell surface proteins. Along with others, 
hyaluronic acid (HA) and gelatin, naturally derived biopolymers have been subjected to numerous studies 
due to their unique structures, and biodegradability under physiological circumstances.
In this study, we developed doxorubicin (DOX) conjugated, gelatin crosslinked HA injectable hydro­
gel (HA-G-DOX) and further analyzed the physicochemical properties o f the biomaterial. The gel prepa­
rations were performed with different molar ratios o f HA, gelatin, and DOX (1:0.1-1:0.05-0.25 mol) in 
diverse volumes and types of solvent systems (water, dioxane, DMSO, and DMF). Optimal conditions for 
obtaining injectable hydrogels with expected physicochemical parameters were selected by combining the 
changeable conditions of the reaction. Washing, centrifugation, and dialysis methods were used to purify 
the obtained hydrogel samples from by-products. The samples were prepared were analyzed structurally 
and physiochemically with IR spectroscopy, UV spectroscopy, rheological testing, scanning electron mi­
croscopy (SEM), and differential scanning calorimetry (DSC) methods. In the IR spectra o f the prepared 
injection hydrogel samples, the characteristic signals corresponding to the O-H, N -H, C6-H, amide-II, 
C -O -C , and C-C bonds from HA, gelatin, and DOX were observed at 3200-3600, 2900, 1556, 1060 and 
600-894 cm-1, respectively. The presence of the HA in the gel was proven by specific signals o f A-acetyl 
group C=O appeared at 1659 cm-1 and by carboxylate ion C=O bonds at 1633 cm-1. In addition, character­
istic signals for the symmetric and asymmetric valence vibrations of DOX C=O and С=С (aromatic ring) 
were observed at 1721 cm-1 and 1560-1650 cm-1, respectively, indicating the existence o f the drug in the 
hydrogel. Changes in the intensity of peaks from amide (I/II/III) bonds at 1310-1558 cm-1 are evincible for 
the presence of gelatin in the material. The loaded DOX amounts (0.25-0.5%, wet wt.) in the HA-G-DOX 
hydrogels were measured by UV spectrophotometric method. The viscosimetric studies indicated that the 
hydrogels prepared possess 2.3-4.7 P a s at 25°C (62.5 rpm). SEM observations demonstrated that the hy­
drogel samples have morphological structures having latticed porosity, which are typical for polysaccha­
ride-based hydrogels. In the DSC analyses, HA-G-DOX hydrogels exhibited stability differing from the 
starting materials.
In summary, DOX conjugated, gelatin crosslinked HA-G-DOX hydrogels were developed and char­
acterized by physicochemical properties. The presence of the parent materials with chemical bondings in
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the gel materials was proven by the instrumental methods. Morphological studies demonstrated that the 
hydrogel samples have structures with latticed porosity, which are typical for polysaccharide-based hydro­
gels. The samples prepared are under investigation regarding their in vitro and in vivo biological properties.