Implementation of Quality by Design (QbD) approach in development of silver sulphadiazine loaded egg oil organogel: An improved dermatokinetic profile and therapeutic efficacy in burn wounds.

Silver Sulphadiazine (SSD) is an effective antibacterial agent considered as the gold standard for burn wound treatment. The present study aimed to investigate EO-based organogel (SSD-EOOG) as an effective carrier system for SSD delivery in burn wound management employing Quality by Design (QbD) paradigm. The organogel-based formulations were prepared employing QbD-oriented approach and further evaluated for in vivo efficacy and stability. The developed formulations were characterized for particle size, drug content, morphology, in vitro drug release, skin safety studies, ex vivo permeation, skin retention, textural analysis and pharmacodynamic studies in murine burn wound model. I-optimal mixture design was employed for optimization and evaluating different critical quality attributes (CQAs). The optimized formulation exhibited particle size of 256.5 nm with enhanced permeation (72.33 ± 1.73%) and retention (541.20 ± 22.16 µg/cm2) across skin barrier as compared to SSD-MKT. The pharmacodynamic results proved superior therapeutic efficacy of SSD-EOOG in topical burn wounds inflicted with MRSA bacterium. The results indicated wound contraction rate (78.23 ± 5.65%) and faster re-epithelialization in SSD-EOOG treated group. The present study concluded that egg oil based organogel promoted therapeutic efficacy of SSD for burn wound treatment.

Highly water-dispersible silver sulfadiazine decorated with polyvinyl pyrrolidone and its antibacterial activities.

Highly water-dispersible silver sulfadiazine (SSD) was prepared by liquid phase method with polyvinyl pyrrolidone (PVP) as a surface modification agent. The structure and morphology of the PVP-modified silver sulfadiazine (P-SSD) were investigated by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and Fourier-transform infrared (FT-IR) spectrometry. The produced particles are ginkgo leaf-like architecture with the sizes of micron-nanometer. Due to hydrophilic PVP decorated on the surface, the P-SSD has excellent dispersion in water over a period of 24h, which is obviously stable by comparison to that of the commercial silver sulfadiazine (C-SSD). In addition, the P-SSD exhibits good antibacterial activities against Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus).

Production and characterization of cornstarch/cellulose acetate/silver sulfadiazine extrudate matrices.

The production and evaluation of cornstarch/cellulose acetate/silver sulfadiazine extrudate matrices are reported herein. The matrices were melt extruded under nine different conditions, altering the temperature and the screw speed values. The surface morphology of the matrices was examined by scanning electron microscopy. The micrographs revealed the presence of non-melted silver sulfadiazine microparticles in the matrices extruded at lower temperature and screw speed values. The thermal properties were evaluated and the results for both the biopolymer and the drug indicated no thermal degradation during the melt extrusion process. The differential scanning analysis of the extrudate matrices showed a shift to lower temperatures for the silver sulfadiazine melting point compared with the non-extruded drug. The starch/cellulose acetate matrices containing silver sulfadiazine demonstrated significant inhibition of the growth of Pseudomonas aeruginosa and Staphylococcus aureus. In vivo inflammatory response tests showed that the extrudate matrices, with or without silver sulfadiazine, did not trigger chronic inflammatory processes.

Anti-inflammatory and antioxidant effects of Aloe saponaria Haw in a model of UVB-induced paw sunburn in rats.

Ultraviolet B (UVB) irradiation mainly affects biological tissues by inducing an increase in reactive oxygen species (ROS) production which leads to deleterious outcomes for the skin, including pain and inflammation. As a protective strategy, many studies have focused on the use of natural products. The aim of this study was to investigate the effects of Aloe saponaria on nociceptive, inflammatory, and oxidative parameters in a model of UVB-induced sunburn in adult male Wistar rats. Sunburned animals were topically treated with vehicle (base cream), 1% silver sulfadiazine (positive control) or A. saponaria (10%) once a day for 6days. UVB-induced nociception (allodynia and hyperalgesia), inflammation (edema and leukocyte infiltration) and oxidative stress (increases in H2O2, protein carbonyl levels and lipid peroxidation and a decrease in non protein thiol content) were reduced by both A. saponaria and sulfadiazine topical treatment. Furthermore, A. saponaria or its constituents aloin and rutin reduced the oxidative stress induced by H2O2 in skin homogenates in vitro. Our results demonstrate that topical A. saponaria treatment displayed anti-nociceptive and anti-inflammatory effects in a UVB-induced sunburn model, and these effects seem to be related to its antioxidant components.

Nanohybrids of silver particles immobilized on silicate platelet for infected wound healing.

Silver nanoparticles supported on nanoscale silicate platelets (AgNP/NSP) possess interesting properties, including a large surface area and high biocide effectiveness. The nanohybrid of AgNP/NSP at a weight ratio 7/93 contains 5-nm Ag particles supported on the surface of platelets with dimensions of approximately 80×80×1 nm(3). The nanohybrid expresses a trend of lower cytotoxicity at the concentration of 8.75 ppm Ag and low genotoxicity. Compared with conventional silver ions and the organically dispersed AgNPs, the nanohybrid promotes wound healing. We investigated overall wound healing by using acute burn and excision wound healing models. Tests on both infected wound models of mice were compared among the AgNP/NSP, polymer-dispersed AgNPs, the commercially available Aquacel, and silver sulfadiazine. The AgNP/NSP nanohybrid was superior for wound appearance, but had similar wound healing rates, vascular endothelial growth factor (VEGF)-A levels and transforming growth factor (TGF)-ß1 expressions to Aquacel and silver sulfadiazine.

Ultrastructural localization and chemical binding of silver ions in human organotypic skin cultures.

Organotypic cultures of human breast skin incubated with silver bandage or treated with silver sulfadiazine accumulated silver in epithelial cells and in macrophages, fibroblasts and collagen fibrils and fibres of underlying connective tissue. Ultrastructurally, the accumulated silver was found in lysosome-like vesicles of the different cells and evenly spread along collagen structures. Apoptotic nuclei were present but few. Autometallographic amplification of 2D-PAGE gels revealed that glutathione S-transferase and glutathion detoxify silver ions in the epidermal cell by binding them in silver-sulphur nanocrystals. Thus, the cytotoxic effect of silver ions seems to be muted by silver ions by being: (1) taken up by undamaged cells, neutralised by glutathione (GSH) and accumulated in lysosomal vesicles, (2) bound extracellularly to SH-groups of the collagen fibres.

A new silver sulfadiazine water soluble gel.

Silver sulfadiazine is the most commonly used topical antibacterial agent for the treatment of burn wounds. It has many clinical advantages, including a broad spectrum of antimicrobial activity, low toxicity, and minimal pain on application. The current formulation of silver sulfadiazine contains a lipid soluble carrier, polypropylene glycol, that has certain disadvantages, including pseudo-eschar formation and the need for twice daily application. The purpose of this investigation was to describe a new formulation of silver sulfadiazine in a water soluble gel, poloxamer 188. The antibacterial activity of this new gel has been compared to that of the commercially available silver sulfadiazine cream by in vitro and in vivo testing. The results of the in vitro antibacterial testing of these two different agents demonstrated the superiority of the new gel formulation. In experimental wounds, the antibacterial activity of the gel and the commercially available silver sulfadiazine cream were not significantly different when applied once a day. The antibacterial activity of the gel when applied once a day was comparable to that encountered by twice daily applications of the silver sulfadiazine cream by experimental wounds. The major advantage of this gel was its ease of application and removal that is attributed to its water solubility.

Solubility of silver sulfadiazine in physiological media and relevance to treatment of thermal burns with silver sulfadiazine cream.

Silver sulfadiazine cream has been a standard treatment for burns over the past two decades. Although many studies have described the phenomenon of silver absorption from burn wounds treated with silver sulfadiazine, they failed to examine the chemistry underlying the absorption process: Silver chloride was assumed to form at the burn wound and absorption of silver was believed to be negligible. Here we have developed chemical model systems to investigate the interactions of silver sulfadiazine and silver chloride in direct contact with synthetic serum electrolyte solution (SSES), with SSES plus endogenous ligands or beef blood plasma, and with human serum. The results indicate that silver absorption from an acute burn site can be significant, because human serum is capable of solubilizing silver. This finding is of concern, given the potential for silver toxicity as a direct consequence of applying silver sulfadiazine to extensive burn wounds.