Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds

Abstract

Diabetic hyperglycemia delays wound healing, leading to serious consequences. Topical antibiotics can reduce the risk of a wound infection during healing; nevertheless, the microbial fight against antibiotics brings about public health challenges. Anti-microbial peptides (AMPs) belong to a novel class of drug that is used to prevent and treat systemic and topical infections. The aim of the current work was to achieve better wound healing in diabetic rats by conjugating the anti-microbial peptide “apamin” (APA) with the broad-spectrum antibiotic “ceftriaxone” (CTX) to form a nanocomplex. The CTX–APA nanoconjugate formulation was optimized using a Box–Behnken design. The optimized CTX–APA nanoconjugate formulation was evaluated for its size and zeta potential, and was then examined using transmission electron microscopy (TEM). The CTX–APA nanoconjugate was loaded onto a hydroxypropyl methylcellulose (2% w/v)-based hydrogel. It was observed that the application of the CTX–APA nanocomplex on the wounded skin of diabetic rats accelerated the regeneration of the epithelium, granulation tissue formation, epidermal proliferation, and keratinization. The nanocomplex was capable of significantly reducing the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), while increasing the expression of transforming growth factor beta-1 (TGF-β1) as well as the angiogenic markers: hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Conclusively, the application of an ion-paired CTX–APA nanocomplex enhances wound healing in diabetic rats.

Cordycepin- melittin nanoconjugate intensifies wound healing efficacy in diabetic rats

“…The dried skins were then weighed and homogenized in phosphate-buffered saline (PBS) solution for obtaining 10% w/v tissue homogenates. The homogenate tissue was then centrifuged at 3000 rpm for 20 min at 4 °C, followed by the collection of supernatants which was then analyzed for the estimation of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and hydroxyproline ( Alamoudi et al, 2022 , Musalmah et al, 2002 ).…”

Wound Gel with Antimicrobial Effects Based on Polyvinyl Alcohol and Functional Aryloxycyclotriphosphazene

“…This is due to their ability to absorb a large amount of water or biological fluids [6,7], pH sensitivity [8], temperature [9], ease of application to the wound surface, and their ability to maintain their three-dimensional structure without dissolution. Furthermore, they create a humid environment, allow oxygen diffusion into the wound, adsorb wound exudate, and act as a protective barrier against microorganisms [10]. Hydrogels create the desired microenvironment for the proliferation and differentiation of dermal fibroblasts, promoting angiogenesis, effective tissue repair, and skin regeneration [11].…”

Polymeric Gel Systems Cytotoxicity and Drug Release as Key Features for their Effective Application in Various Fields of Addressed Pharmaceuticals Delivery

“…Hydrogels 20–30 nm in size (“nanogels”) are capable of incorporating hydrophobic drugs into the core and delivering them to their destination, providing their prolonged release. In particular, hydrogel delivery systems for enzymes [ 6 ], proteins [ 7 ], antibiotics [ 8 , 9 , 10 , 11 ], adenoviruses [ 12 ], anticancer drugs, for example, doxorubicin [ 13 , 14 , 15 ], paclitaxel [ 16 ], 5-fluorouracil [ 17 , 18 , 19 ], kaempferol [ 20 ], vincristine [ 21 ], oxaliplatin [ 22 ], cyclophosphamide [ 23 ], carmustine and curcumin [ 24 ], drugs for the treatment of skin diseases [ 25 , 26 , 27 ], anesthetics for the treatment of acute postoperative pain [ 28 ], antimicrobial silver nanoparticles and quantum dots for wound healing [ 29 , 30 ] are known and studied currently. The rate of release of these mentioned drugs from hydrogels is affected by the degree of cross-linking and the degree of swelling of the hydrogels.…”