Investigation of the Potential of Nebivolol Hydrochloride-Loaded Chitosomal Systems for Tissue Regeneration: In Vitro Characterization and In Vivo Assessment.

Noha Ibrahim Elsherif,Rehab Nabil Shamma,Abdulaziz Mohsen Al-Mahallawi,Abdelfattah Ahmed Abdelkhalek

doi:10.3390/pharmaceutics13050700

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.

Highlights

Introduction iationsSmall diffusible molecules like nitric oxide (NO) play an important role in wound repair and tissue regeneration [1], as confirmed by an elevated level of NO in wounds [2,3,4].NO has been shown to activate angiogenesis and promotes fibroplasia [5]
Ionic gelation method as described by Berthold et al was the method of choice for preparing Nebivolol hydrochloride (NVH)-loaded chitosomes, as they reported the preparation of chitosan–TPP complex by adding chitosan acidic solution into a TPP solution in a dropwise manner [42]
Neither harmful chemicals nor critical operations are required in this process and it is very simple and mild [70]; this method is one of the most common methods described for the formation of chitosomes in the literature [43,71,72,73]

Summary

Introduction

Introduction iationsSmall diffusible molecules like nitric oxide (NO) play an important role in wound repair and tissue regeneration [1], as confirmed by an elevated level of NO in wounds [2,3,4].NO has been shown to activate angiogenesis and promotes fibroplasia [5]. Small diffusible molecules like nitric oxide (NO) play an important role in wound repair and tissue regeneration [1], as confirmed by an elevated level of NO in wounds [2,3,4]. NVH is a third-generation beta-blocker approved by the FDA for the treatment of hypertension. It exerts its vasodilating effects via NO pathway by releasing cardiovascular endothelial NO [7], in addition to its conventional beta-blocking effects [8]. NVH causes endothelium dependent vasodilatation associated with the activation of L-arginine/nitric oxide pathway in both hypertensive and normotensive patients [9,10,11,12]

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