Abstract:
In this study, we evaluated the synergistic effect of nebivolol hydrochloride (NVH), a
third-generation beta-blocker and NO donor drug, and chitosan on the tissue regeneration. Ionic
gelation method was selected for the preparation of NVH-loaded chitosomes using chitosan lactate
and sodium tripolyphosphate. The effect of different formulation variables was studied using a
full factorial design, and NVH entrapment efficiency percentages and particle size were selected
as the responses. The chosen system demonstrated high entrapment efficiency (73.68 ± 3.61%),
small particle size (404.05 ± 11.2 nm), and good zeta potential value (35.6 ± 0.25 mV). The best-
achieved formula demonstrated spherical morphology in transmission electron microscopy and
amorphization of the crystalline drug in differential scanning calorimetry and X-ray diffraction. Cell
culture studies revealed a significantly higher proliferation of the fibroblasts in comparison with the
drug suspensions and the blank formula. An in vivo study was conducted to compare the efficacy of
the proposed formula on wound healing. The histopathological examination showed the superiority
of NVH-loaded chitosomes on the wound proliferation and the non-significant difference in the
collagen deposition after 15 days of the injury to that of intact skin. In conclusion, NVH-loaded
chitosomes exhibited promising results in enhancing skin healing and tissue regeneration.
