Erythropoietin-isosorbide dinitrate-loaded nanocomplex cryogel scaffold: a multifunctional smart dressing for...

Multifunctional scaffolds hold significant promise for enhancing tissue regeneration, delivering therapeutics, and responding dynamically to physiological cues, particularly in chronic wounds like diabetic ulcers. In the current work, chitosan (CS)/unfractionated heparin (UFH) nanocomplex dispersions loaded with Erythropoietin (EPO) and isosorbide dinitrate (ISDN) was used to prepare a multifunctional cryogel.

CS/UFH mass ratios of 0.5:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 8:1, and 10:1 were used to prepare nanocomplex dispersions. The prepared dispersions were characterized using physicochemical (DLS, zeta potential, FT-IR spectroscopy) and morphological (TEM and SEM) analyses. The effect of CS/UFH mass ratio as well as pH on the release was also studied. Finally, a stability study was conducted to identify the effect of long-term storage in refrigerated conditions on the formulation.

The optimal formulation at a CS/UFH ratio of 5:1 exhibited favourable characteristics (size: 247 nm, PDI: 0.223, zeta potential: +43.3 mV, EE%: 59.4). TEM imaging consolidated the particle size detected. FT-IR analysis confirmed the electrostatic interaction between CS amino groups, and sulphate and carboxylate groups of EPO and UFH, respectively. Morphological analysis of the cryogel revealed a highly porous structure with large voids. Release experiments indicated a fast ISDN release over 6-8 h with a sustained release of EPO over 4 days. The stability study did not detect any deleterious effect on the physical form or active content over six months.

Our findings demonstrate that the developed cryogel may enhance diabetic wound healing through the sustained delivery of EPO and ISDN.