Enhanced healing efficacy of an optimized gabapentin-melittin nanoconjugate gel-loaded formulation in excised wounds of diabetic rats

Abstract

The present study aimed to design and optimize, a nanoconjugate of gabapentin (GPN)-melittin (MLT) and to evaluate its healing activity in rat diabetic wounds. To explore the wound healing potency of GPN-MLT nanoconjugate, an in vivo study was carried out. Diabetic rats were subjected to excision wounds and received daily topical treatment with conventional formulations of GPN, MLT, GPN-MLT nanoconjugate and a marketed formula. The outcome of the in vivo study showed an expedited wound contraction in GPN-MLT-treated animals. This was confirmed histologically. The nanoconjugate formula exhibited antioxidant activities as evidenced by preventing malondialdehyde (MDA) accumulation and superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic exhaustion. Further, the nanoconjugate showed superior anti-inflammatory activity as it inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). This is in addition to enhancement of proliferation as indicated by increased expression of transforming growth factor-β (TGF- β), vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor receptor-β (PDGFRB). Also, nanoconjugate enhanced hydroxyproline concentration and mRNA expression of collagen type 1 alpha 1 (Col 1A1). In conclusion, a GPN-MLT nanoconjugate was optimized with respect to particle size. Analysis of pharmacokinetic attributes showed the mean particle size of optimized nanoconjugate as 156.9 nm. The nanoconjugate exhibited potent wound healing activities in diabetic rats. This, at least partly, involve enhanced antioxidant, anti-inflammatory, proliferative and pro-collagen activities. This may help to develop novel formulae that could accelerate wound healing in diabetes.

Cordycepin- melittin nanoconjugate intensifies wound healing efficacy in diabetic rats

“…This was confirmed via histological examination which disclosed that COR-MEL nanoconjugate -treated rats showed almost complete healing on the 14th day with tissue regeneration and collagen deposition. The results are associated with earlier statements highlighting the synergistic wound-healing activity of MEL when combined with other drugs ( Alhakamy et al, 2021 , Asfour et al, 2022 , Eid et al, 2022 , Kim et al, 2021a , Maiden et al, 2019 ).…”

“…In addition, COR expedites the tissue remodeling process ( Kim et al, 2021a , Kim et al, 2021b ) Melittin (MEL), an aqueous–soluble cationic peptide, consisting of 26 amino acids with no disulfide bridges, is obtained from the crude venom of honeybees. MEL possesses pharmacological activities against inflammation, oxidative stress, and multi-resistance infection of bacteria in addition to pro-collagen activity ( Asfour et al, 2022 , Tiwari et al, 2022 ). Its anti-inflammatory activities are supported by several reports showing that MEL reduces the expression of cyclooxygenase (COX)-2 and phospholipase A2, as well as the levels of TNF-α, IL-1, IL-6, nitric oxide (NO), and ROS.…”

“…Its anti-inflammatory activities are supported by several reports showing that MEL reduces the expression of cyclooxygenase (COX)-2 and phospholipase A2, as well as the levels of TNF-α, IL-1, IL-6, nitric oxide (NO), and ROS. Further, it impedes the nuclear factor kappa B (NF-κβ) signaling ( Asfour et al, 2022 , Eid et al, 2022 , Tiwari et al, 2022 ). It was further revealed that based on the pharmacological advantages of MEL, it has been formulated as a topical preparation to facilitate wound healing ( Asfour et al, 2022 ).…”

“…Further, it impedes the nuclear factor kappa B (NF-κβ) signaling ( Asfour et al, 2022 , Eid et al, 2022 , Tiwari et al, 2022 ). It was further revealed that based on the pharmacological advantages of MEL, it has been formulated as a topical preparation to facilitate wound healing ( Asfour et al, 2022 ).…”

Polycaprolactone based pharmaceutical nanoemulsion loaded with acriflavine: optimization andin vivoburn wound healing activity

“…The particle size, zeta potential, and polydispersity of ACR-PCL-NE were monitored for 90 days (fresh, 30 days, 60 days, and 90 days). The ACR-PCL-NE was stored at 25 °C throughout the course (Romes et al., 2021 ; Asfour et al., 2022 ; Mushtaq et al., 2022 ).…”