Sustainable Release of Propranolol Hydrochloride Laden with Biconjugated-Ufasomes Chitosan Hydrogel Attenuates Cisplatin-Induced Sciatic Nerve Damage in In Vitro/In Vivo Evaluation

Abstract

Peripheral nerve injuries significantly impact patients’ quality of life and poor functional recovery. Chitosan–ufasomes (CTS–UFAs) exhibit biomimetic features, making them a viable choice for developing novel transdermal delivery for neural repair. This study aimed to investigate the role of CTS–UFAs loaded with the propranolol HCl (PRO) as a model drug in enhancing sciatica in cisplatin-induced sciatic nerve damage in rats. Hence, PRO–UFAs were primed, embedding either span 20 or 60 together with oleic acid and cholesterol using a thin-film hydration process based on full factorial design (24). The influence of formulation factors on UFAs’ physicochemical characteristics and the optimum formulation selection were investigated using Design-Expert® software. Based on the optimal UFA formulation, PRO–CTS–UFAs were constructed and characterized using transmission electron microscopy, stability studies, and ex vivo permeation. In vivo trials on rats with a sciatic nerve injury tested the efficacy of PRO–CTS–UFA and PRO–UFA transdermal hydrogels, PRO solution, compared to normal rats. Additionally, oxidative stress and specific apoptotic biomarkers were assessed, supported by a sciatic nerve histopathological study. PRO–UFAs and PRO–CTS–UFAs disclosed entrapment efficiency of 82.72 ± 2.33% and 85.32 ± 2.65%, a particle size of 317.22 ± 6.43 and 336.12 ± 4.9 nm, ζ potential of −62.06 ± 0.07 and 65.24 ± 0.10 mV, and accumulatively released 70.95 ± 8.14% and 64.03 ± 1.9% PRO within 6 h, respectively. Moreover, PRO–CTS–UFAs significantly restored sciatic nerve structure, inhibited the cisplatin-dependent increase in peripheral myelin 22 gene expression and MDA levels, and further re-established sciatic nerve GSH and CAT content. Furthermore, they elicited MBP re-expression, BCL-2 mild expression, and inhibited TNF-α expression. Briefly, our findings proposed that CTS–UFAs are promising to enhance PRO transdermal delivery to manage sciatic nerve damage.

The Effect of Adipose-Derived Mesenchymal Stem Cells on Peripheral Nerve Damage in a Rodent Model

“…Therefore, MDA may negatively affect the regeneration process after nerve damage and inhibit the healthy regeneration of nerve cells. Many studies have tried many antioxidants to prevent damage to MDA [26,27]. In this study, ADSCs, other than antioxidants, prevent peroxidation and protect against nerve damage by decreasing MDA levels.…”

Novel Bile Salt Stabilized Vesicles-Mediated Effective Topical Delivery of Diclofenac Sodium: A New Therapeutic Approach for Pain and Inflammation

“…It is noteworthy that the obtained size by TEM is lower than that size obtained from the dynamic light scattering technique (DLS) approach utilizing a Zetasizer NanoZS 7.11 (Malvern Instruments, Malvern, UK) because the analytical principle used was different in both techniques. DLS is an intensity-based technique in which the size distribution result is the hydrodynamic size average of the nanoparticles and is frequently impacted by the presence of aggregates, large particles or dust [60]. Particularly, the nanovesicles evaluated using DLS techniques are in solution and surrounded by layers of the medium used, which increases their measurement size.…”

“…However, microscopic examination by TEM relies heavily on nanoparticle tracking analysis (NTA), and the observation of a nanoparticle containing a droplet on a TEM grid is often performed after the routine drying method of air drying. Individual nanoparticles are tracked using NTA, a numerically based method (single-particle tracking) [60]. Thus, the latter can deliver a precise number-based average dimension with little bias for pure samples [61].…”

“…Pharmaceuticals 2022, 15, x FOR PEER REVIEW 12 of 30 numerically based method (single-particle tracking) [60]. Thus, the latter can deliver a precise number-based average dimension with little bias for pure samples [61].…”

Therapeutic potential of luteolin-loaded poly(lactic-co-glycolic acid)/modified magnesium hydroxide microsphere in functional thermosensitive hydrogel for treating neuropathic pain

“…As a result, numerous studies are exploring alternative approaches to Dex administration approaches. 10 – 12 …”