In vitro and in vivo evaluation of biologically synthesized silver nanoparticles for topical applications: effect of surface coating and loading into hydrogels

Aml I Mekkawy,1 Mohamed A El-Mokhtar,2 Nivien A Nafady,3 Naeima Yousef,3 Mostafa A Hamad,4 Sohair M El-Shanawany,5 Ehsan H Ibrahim,5 Mahmoud Elsabahy5–8 1Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag, 2Department of Microbiology and Immunology, Faculty of Medicine, 3Department of Botany and Microbiology, Faculty of Science, 4Department of Surgery, Faculty of Medicine, 5Department of Pharmaceutics, Faculty of Pharmacy, 6Assiut International Center of Nanomedicine, Al-Rajhi Liver Hospital, Assiut University, Assiut, Egypt; 7Laboratory for Synthetic-Biologic Interactions, Department of Chemistry, Texas A&M University, College Station, TX, USA; 8Misr University for Science and Technology, 6th of October, Egypt Abstract: In the present study, silver nanoparticles (AgNPs) were synthesized via biological reduction of silver nitrate using extract of the fungus Fusarium verticillioides (green chemistry principle). The synthesized nanoparticles were spherical and homogenous in size. AgNPs were coated with polyethylene glycol (PEG) 6000, sodium dodecyl sulfate (SDS), and β-cyclodextrin (β-CD). The averaged diameters of AgNPs were 19.2±3.6, 13±4, 14±4.4, and 15.7±4.8 nm, for PEG-, SDS-, and ß-CD-coated and uncoated AgNPs, respectively. PEG-coated AgNPs showed greater stability as indicated by a decreased sedimentation rate of particles in their water dispersions. The antibacterial activities of different AgNPs dispersions were investigated against Gram-positive bacteria (methicillin-sensitive and methicillin-resistant Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) by determination of the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). MIC and MBC values were in the range of 0.93–7.5 and 3.75–15 µg/mL, respectively, which were superior to the reported values in literature. AgNPs-loaded hydrogels were prepared from the coated-AgNPs dispersions using several gelling agents (sodium carboxymethyl cellulose [Na CMC], sodium alginate, hydroxypropylmethyl cellulose, Pluronic F-127, and chitosan). The prepared formulations were evaluated for their viscosity, spreadability, in vitro drug release, and antibacterial activity, and the combined effect of the type of surface coating and the polymers utilized to form the gel was studied. The in vivo wound-healing activity and antibacterial efficacy of Na CMC hydrogel loaded with PEG-coated AgNPs in comparison to the commercially available silver sulfadiazine cream (Dermazin®) were evaluated. Superior antibacterial activity and wound-healing capability, with normal skin appearance and hair growth, were demonstrated for the hydrogel formulations, as compared to the silver sulfadiazine cream. Histological examination of the treated skin was performed using light microscopy, whereas the location of AgNPs in the skin epidermal layers was visualized using transmission electron microscopy. Keywords: silver nanoparticles, green synthesis, coating agents, hydrogel, wound healing, antibacterial activit

Cellulose-based hydrogels for wound healing

Wound healing is a dynamic process involving several intra/extracellular mechanisms, which are triggered by cutaneous injuries. Wound repair consists of three separate but overlapping phases, i.e., inflammation, formation of new tissue, and remodeling. Although wound healing is an innate ability of every multicellular organism, specific precautions are required in some particular cases. One important aspect of wound management is maintaining a good level of moisture. It has been acknowledged by the medical community that an optimal level of hydration leads to increased healing rates, reduces pain, and improves cosmesis. In this context, it is essential to know the nature of the wound in order to choose the most suitable wound dressing. For instance, in the presence of a dry wound, where additional hydration is necessary, the use of highly hydrated hydrogels can allow the autolytic debridement of necrotic tissue when its surgical removal is not feasible. The ability to trap water up to thousand times their dry weight turns these materials into valid alternatives for wound healing applications. The use of cellulose-based hydrogels has become popular owing to their great degree of biocompatibility, low-cost, and biodegradability. Recently, different strategies have been investigated for the development of more efficient wound dressings, for instance, the introduction of antibacterial features using a combination of antibiotics and/or antibacterial polymers. Along with plant-derived cellulose, the use of bacterial cellulose membranes as wound dressings and skin substitutes is attracting considerable interest due to their innate hydrogel structure as well as their high chemical purity and mechanical properties. This chapter will present an overview of the most recent studies on cellulose-based hydrogels for wound healing applications, as well as the most recent outcomes of research in this field