Dual Drug Delivery for Augmenting Bacterial Wound Complications via Tailored Ultradeformable Carriers.

Addressing the complex challenge of healing of bacterially infected wounds, this study explores the potential of lipid nanomaterials, particularly advanced ultradeformable particles (UDPs), to actively influence the wound microenvironment. The research introduces a novel therapeutic approach utilizing silver sulfadiazine (SSD) coupled with vitamin E (VE) delivered through UDPs (ethosomes/transferosomes/transethosomes). Comparative physicochemical characterization of these nanosized drug carriers reveals the superior stability of transethosomes, boasting a zeta potential of -36.5 mV. This method demonstrates reduced side effects compared to conventional therapies, with almost 90% SSD and 72% VE release achieved in wound pH in a sustained manner. Cytotoxicity assessment shows 60% cell viability even at the highest concentration (175 µg/mL), while hemolysis test demonstrates RBC lysis below 5% at a concentration of 250 µg/mL. Vitamin E-SSD-loaded transethosomes (VSTEs) significantly enhance cellular migration and proliferation, achieving 95% closure within 24 h, underscoring their promising efficacy. The synergistic method effectively reduces bacterial burden, evidenced by an 80% reduction in Escherichia coli and Staphylococcus aureus within the wound microenvironment. This approach offers a promising strategy to address complications associated with skin injuries.

Physicochemical Characterization of Silver Sulfadiazine in Polymeric Wound Dressings.

The insertion of topical antimicrobials in wound treatment represented an important role in patient management. Among these agents, silver sulfadiazine (AgSD), introduced in the therapy of wounds and burns in the 1960s, is considered the gold standard in treatment due to its mechanism of action, in addition to its proven efficacy and safety. The association of AgSD with polymers for the development of curative formulations has been reported. The evaluation of the physical-chemical properties of these systems with the aid of analytical techniques of characterization is essential for the determination of their activities, besides allowing the detection of possible incompatibilities between AgSD and polymers. Thus, this review presents the main techniques of physicochemical characterization used in the evaluation of systems containing AgSD with curative purposes in order to provide parameters to ensure the efficacy and safety of these new therapeutic options. Microscopic, thermoanalytical, and spectroscopic techniques, for example, provide information on system properties such as surface chemical composition, crystallinity, morphology, and thermal stability of curative formulations containing AgSD. These techniques are important in the selection of the most appropriate techniques during the development of a polymeric curative system containing AgSD, in addition to providing information for cost reduction of a possible scale-up and the establishment of methodologies for quality control of these systems to ensure their efficacy and safety.

Natural rubber dressing loaded with silver sulfadiazine for the treatment of burn wounds infected with Candida spp.

Millions of people are burned worldwide every year and 265,000 of the cases are fatal. The development of burn treatment cannot consist only of the administration of a single drug. Due to the infection risk, antibiotics are used in conjunction with gels and damp bandages. In this work, an inexpensive curative based on silver sulfadiazine (SS) and natural rubber latex (NRL) was developed to treat burn wounds. It was produced by the casting method. The infrared spectrum presented no interaction between drug and biopolymer. At the same time, electronic micrographs showed that the SS crystals are inserted on the polymeric dressing surface. Mechanical properties after the drug incorporation were considered suitable for dermal application. About 32.4% of loaded SS was released in 192 h by the dressings that also inhibited the growth of Candida albicans and Candida parapsilosis at 75.0 and 37.5 µg·mL-1, respectively. The curative proved to be biocompatible when applied to fibroblast cells, in addition to enhancing cellular proliferation and, in the hemocompatibility test, no hemolytic effects were observed. The good results in mechanical, antifungal and biological assays, combined with the average bandage cost of $0.10, represent an exciting alternative for treating burn wounds.

Antimicrobial dressing of silver sulfadiazine-loaded halloysite/cassava starch-based (bio)nanocomposites.

(Bio)nanocomposites have been studied for biomedical applications, including the treatment of wounds. However, wound infection is one of the main problems of wound care management, and the use of wound dressings with antibacterial agents is essential. This work focused on developing and characterizing silver sulfadiazine-loaded halloysite/cassava starch-based (bio)nanocomposites potentially suitable as antimicrobial dressing. Silver sulfadiazine was complexed inside the halloysite nanotubes lumen, and the drug-loaded nanotubes were incorporated in thermoplastic starch dispersion, forming the (bio)nanocomposites. The silver sulfadiazine-loaded halloysite and the (bio)nanocomposite were characterized by zeta potential, scanning electron microscopy, X-ray diffraction, and infrared spectroscopy. The dressing properties of (bio)nanocomposites (water vapor permeability and mechanical stability) and their antimicrobial efficacy by Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were also evaluated. Physicochemical studies suggested the silver sulfadiazine-loaded halloysite complexation (zeta potential of -38.9 mV) and its interactions with the starch forming the nanocomposites. The silver sulfadiazine-loaded halloysite/starch-based (bio)nanocomposites possessed a homogeneous and organized structure. Also, they had mechanical properties to be used as a dressing (13.73 ± 3.09 MPa and 3.17 ± 1.28% of elongation at break), and its permeability (6.18 ± 0.43 (10-13) g.Pa-1.s-1.m-1) could be able to maintain the environmental moisture at the wound surface. Besides that, the (bio)nanocomposites acted against the studied bacteria, being a potential contact antimicrobial and biodegradable wound dressing. Finally, the developed (bio)nanocomposites are semi-occlusive and good candidates for dry wounds to be widely in vitro and in vivo tested as controlled silver sulfadiazine delivery dressing.

Silver sulfadiazine loaded breathable hydrogel sponge for wound healing.

Objectives Patients with serious injury need special care and treatment to control the infection, as wound sepsis is one of the major causes of death. Silver sulfadiazine (SSD) is widely used as an antimicrobial agent which promotes healing and re-epithelialization. However, due to certain drawbacks such as inflammation and cytotoxicity, the need for novel drug delivery modality emerges. The objective of this study was to develop natural polymeric (chitosan and gelatin) hydrogel sponges containing SSD and evaluate its efficacy in wound healing using animal models. Methods SSD containing hydrogel sponges were prepared by solvent casting technique. Scanning electron microscopy (SEM) and Differential scanning calorimetry (DSC) were used to evaluate morphological characteristics of the hydrogel sponges. Anti-thrombogenic property, drug release studies, drug release kinetics, antimicrobial property, and wound healing effect were also studied in detail. Results The optimized batch of hydrogel sponges (CG4) consists of 1% SSD wt., 10% wt. Gelatin, 1% wt. Chitosan and honey 7.5% wt. as plasticizer. At the 12th hour, in vitro and ex vivo drug release was found to be 76.994±0.67% and 24.22±0.57% respectively. CG4 batch had enhanced in vitro antimicrobial activity as compared to conventional marketed cream. The developed SSD hydrogel sponges showed a faster rate of wound healing as compared to a marketed cream. Animals treated with CG4 formulation showed complete angiogenesis and re-epithelialization by 8th day, whereas 12 days were required for complete wound healing with marketed cream. Conclusions The prepared hydrogel sponges can serve as a potential alternative for wound healing dressing as compared to the marketed product.

Supramolecular polyelectrolyte complexes based on cyclodextrin-grafted chitosan and carrageenan for controlled drug release.

In the present study, supramolecular polyelectrolyte complexes (SPEC) based on a cyclodextrin-grafted chitosan derivative and carrageenan were prepared and evaluated for controlled drug release. Samples were characterized by FTIR, SEM, and ζ-potential measurements, which confirmed the formation of the polymeric complex. The phenolphthalein test confirmed the presence and availability of inclusion sites from the attached ßCD. Silver sulfadiazine was used as the model drug and the association with the SPEC was studied by FTIR and computational molecular modeling, using a semi-empirical method. DRS and TEM analyses have shown that Ag+ ions from the drug were reduced to form metallic silver nanostructures. In vitro tests have shown a clear bacterial activity toward Gram-positive bacteria Staphylococcus aureus and Enterococcus durans/hirae and Gram-negative bacteria Klebsiella pneumoniae and Escherichia coli. Finally, this work shows that ßCD-chitosan/carrageenan supramolecular polyelectrolyte complexes hold an expressive potential to be applied as a polymer-based system for controlled drug release.

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.

Combining species sensitivity distribution (SSD) model and thermodynamic index (exergy) for system-level ecological risk assessment of contaminates in aquatic ecosystems.

After reviewing the species- and community-level ecological risk assessments (ERAs) of chemicals in the aquatic environment, the present study attempted to propose a third stage of ERA, i.e., the ecosystem-level ERA. Based on the species sensitivity distribution model (SSD) and thermodynamic theory, the exergy and biomass indicators of communities from various trophic levels (TLs) were introduced to improve ecological connotation of SSDs. The species were classified into three TLs based on algae (TL1), invertebrates (TL2), and vertebrates (TL3), and the weight of each TL was determined based on relative biomass and ß value, which indicated a holistic contribution of each species or community to the ecosystem. Then, a system-level ERA protocol was successfully established, and the community- and system-level ecological risks of 10 typical toxic micro-organic pollutants in the western area of Lake Chaohu and its inflowing rivers were evaluated. System-level ERA curves (ExSSD) were mainly affected by the community-level SSD at TL2 for most chemicals in the present study. The uncertain boundary of ExSSD was mostly related to TLs with a wider uncertain boundary, but had little relation to the weight of each TL. The results of system-level ERAs revealed that dibutyl phthalate had the highest eco-risk, whereas γ-hexachlorocyclohexane presented the lowest eco-risk. Results of the system-level ERA were not fully consistent with the those of community-level ERA owing to the lack of a sufficient dataset, SSD model type, and ecosystem structure, as indicated by the weight of each TL. The successful application of ExSSD in Lake Chaohu signifies the start of the third stage of ERA at the system-level, and it also provides a scientific basis for ecosystem-level ERA, aquatic ecosystem protection, and future water safety management. However, there were some limitations, including sufficient data dependence, neglect of ecological interactions, and neglect of environmental parameters such as natural organic matter. We propose to employ toxicogenomics to enrich the toxicity database, to simulate the interaction using the ecological dynamic model, and to introduce the chemical fate model into the system-level ERA.

Alginate films functionalized with silver sulfadiazine-loaded [Mg-Al] layered double hydroxide as antimicrobial wound dressing.

Alginate (ALG) is an abundant, biocompatible, regenerative, and nontoxic polysaccharide that has potential applications in tissue engineering. Silver sulfadiazine (SDZ) is a topical antibiotic used to control bacterial infection in burns. Aiming to combine the intrinsic alginate characteristics and silver sulfadiazine antimicrobial properties, hydrotalcite ([Mg-Al]-LDH) was used as a host matrix to obtain a system efficient in delivering SDZ from alginate films. SDZ was successfully intercalated in [Mg-Al]-LDH through structural reconstruction. Different solutions were prepared using sodium alginate at 10 wt%, glycerol at 10 wt% as a plasticizer and [Mg-Al]-LDH and [Mg-Al]-LDH/SDZ as fillers at 1 wt% and 5 wt%. Films were obtained by continuous casting and further characterized for their microstructural, mechanical, water barrier and antimicrobial properties. Cytotoxicity tests were also performed on fibroblasts cells. The incorporation of [Mg-Al]-LDH and [Mg-Al]-LDH/SDZ presented neither negative nor positive effects on the mechanical properties and morphology of the alginate films. Moreover, samples containing SDZ exhibited inhibitory activity against S. aureus, E. coli, and S. enterica. The addition of [Mg-Al]-LDH/SDZ even at the highest concentration did not afford a very significant cytotoxicity to the alginate-[Mg-Al]-LDH/SDZ films. These results describe a suitable approach for preparing innovative active wound dressings integrated to efficient drug delivery.

Multi-drug hybrid delivery systems with distinct release profiles based on gelatin/collagen containing vesicles derived from block copolymers.

Hybrid delivery systems can release multiple drugs with different profiles and have several applications, including skin dressing. In this work, the co-solvent technique was used for the preparation of nanometric vesicles based on poly(styrene-b-ethylene oxide) block copolymer (BCPVs) containing adapalene (AD). The BCPVs were incorporated into collagen and gelatin matrices together with free AD and silver sulfadiazine (SSD). The AD content of BCPVs and their release capacity were analyzed by using ultraviolet-visible spectroscopy (UV-Vis). The gelatin and collagen matrices were evaluated for their ability to release AD and SSD through an in vitro release study. The obtained results confirmed that the production of empty and AD-loaded BCPVs was viable. The degree of AD encapsulation in BCPVs was 9.0% and the in vitro test revealed a constant, slow, and prolonged release of AD content from AD-loaded BCPVs. The combination of free and encapsulated multiple drugs in hybrid delivery systems based on gelatin and collagen matrices was shown to act as a skin dressing that combined the progressive release of large amounts of drugs within the first hours of use (to restrict infection) with a more prolonged and slow release of AD to enhance skin healing.

Antibiofilm Potential of Silver Sulfadiazine-Loaded Nanoparticle Formulations: A Study on the Effect of DNase-I on Microbial Biofilm and Wound Healing Activity.

Biofilm resistance is one of the severe complications associated with chronic wound infections, which impose extreme microbial tolerance against antibiotic therapy. Interestingly, deoxyribonuclease-I (DNase-I) has been empirically proved to be efficacious in improving the antibiotic susceptibility against biofilm-associated infections. DNase-I hydrolyzes the extracellular DNA, a key component of the biofilm responsible for the cell adhesion and strength. Moreover, silver sulfadiazine, a frontline therapy in burn wound infections, exhibits delayed wound healing due to fibroblast toxicity. In this study, a chitosan gel loaded with solid lipid nanoparticles of silver sulfadiazine (SSD-SLNs) and supplemented with DNase-I has been developed to reduce the fibroblast cytotoxicity and overcome the biofilm-imposed resistance. The extensive optimization using the Box-Behnken design (BBD) resulted in the formation of SSD-SLNs with a smooth surface as confirmed by scanning electron microscopy and controlled release (83%) for up to 24 h. The compatibility between the SSD and other formulation excipients was confirmed by Fourier transform infrared, differential scanning calorimetry, and powder X-ray diffraction studies. Developed SSD-SLNs in combination with DNase-I inhibited around 96.8% of biofilm of Pseudomonas aeruginosa as compared to SSD with DNase-I (82.9%). In line with our hypothesis, SSD-SLNs were found to be less toxic (cell viability 90.3 ± 3.8% at 100 µg/mL) in comparison with SSD (Cell viability 76.9 ± 4.2%) against human dermal fibroblast cell line. Eventually, the results of the in vivo wound healing study showed complete wound healing after 21 days' treatment with SSD-SLNs along with DNase-I, whereas marketed formulations SSD and SSD-LSNs showed incomplete healing after 21 days. Data in hand suggest that the combination of SSD-SLNs with DNase-I is an effective treatment strategy against the biofilm-associated wound infections and accelerates wound healing.

Silver sulfadiazine nanosuspension-loaded thermosensitive hydrogel as a topical antibacterial agent.

BACKGROUND: Silver sulfadiazine (AgSD) is widely employed as an antibacterial agent for surface burn management. However, the antibacterial activity of AgSD was restrained because of the lower drug solubility and possible cytotoxicity. OBJECTIVE: This study aimed to formulate stable silver sulfadiazine/nanosuspensions (AgSD/NSs) with improved AgSD solubility and prepare a suitable carrier for AgSD/NS delivery. Nanotechnology was used to overcome the low drug dissolution rate of AgSD, while the new carrier loaded with AgSD/NS was assumed to decrease the possible cytotoxicity, enhance antibacterial activity, and promote wound healing. METHODS: AgSD/NSs were prepared by high pressure homogenization method. Poloxamer 407-based thermoresponsive hydrogels were prepared by cold method as carriers of AgSD/NS to obtain AgSD/NS-loaded thermoresponsive hydrogel. Scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were used to measure the physicalchemical properties of AgSD/NSs and AgSD/NS-loaded gel. The cytotoxicity of the AgSD/NS-loaded gel was evaluated using methyl thiazolyltetrazolium assay with L929 mouse fibroblast cell lines. In vitro antibacterial activities of AgSD/NSs and AgSD/NS loaded gel were also measured. RESULTS: Stable AgSD/NSs with an average particle size of 369 nm were formulated while 1.5% P407 was selected as a stabilizer. The optimized AgSD/NS thermoresponsive hydrogel exhibited the gelation temperature of approximately 30°C. A significant improvement in solubility was observed for AgSD nanoparticles (96.7%) compared with AgSD coarse powders (12.5%). The results of FTIR and XRD revealed that the physicochemical properties of AgSD/NS were reserved after incorporating into the hydrogel. The cell viability after incubation with AgSD/NS-loaded thermoresponsive hydrogel improved from 60.7% to 90.6% compared with incubation with AgSD/NS directly. Drug release profiles from the thermoresponsive hydrogel increased compared with the commercial AgSD cream, implying less application frequency of AgSD cream clinically. In vitro antibacterial studies manifested that AgSD nanocrystallization significantly enhanced the antibacterial activity compared with the AgSD coarse powder. CONCLUSION: The combination of AgSD nanosuspensions and thermoresponsive hydrogel effectively improved the AgSD antibacterial activity and decreased the cytotoxicity. This study also suggested that a poloxamer thermoresponsive hydrogel could be used as a delivery system for other nanocrystals to decrease possible nanotoxicity.

Silver sulfadiazine nanoethogel for burn healing: characterization and investigation of its in vivo effects.

AIM: Nanoethosomal formulation containing silver sulfadiazine (SSD) was used to reduce bacterial burden and healing time in burn injuries. MATERIALS & METHODS: Ethosomal formulations were characterized for their size, ζ-potential, morphology, drug encapsulation efficiency and in vitro release kinetics of SSD. RESULTS: The optimized nanoethosomal suspension with a size of 206.7 ± 1.18, and ζ-potential value of -67.3 ± 0.45 mV exhibited a high SSD encapsulation efficiency (92.03 ± 0.79%). Results of antimicrobial tests indicated SSD-loaded ethosome formulation led to a significant reduction of colony number. Histopathological results demonstrated a wound contraction rate of 96.83% for the group treated with SSD ethosomal gel while untreated group showed 59.41%. CONCLUSION: The SSD ethogels promotes the therapeutic effect of SSD for burn treatment.

Electrospun poly(ε-caprolactone) matrices containing silver sulfadiazine complexed with ß-cyclodextrin as a new pharmaceutical dosage form to wound healing: preliminary physicochemical and biological evaluation.

Cooperation between researchers in the areas of medical, pharmaceutical and materials science has facilitated the development of pharmaceutical dosage forms that elicit therapeutic effects and protective action with a single product. In addition to optimizing pharmacologic action, such dosage forms provide greater patient comfort and increase success and treatment compliance. In the present work, we prepared semipermeable bioactive electrospun fibers for use as wound dressings containing silver sulfadiazine complexed with ß-cyclodextrin in a poly(Ɛ-caprolactone) nanofiber matrix aiming to reduce the direct contact between silver and skin and to modulate the drug release. Wound dressings were prepared by electrospinning, and were subjected to ATR-FT-IR and TG/DTG assays to evaluate drug stability. The hydrophilicity of the fibrous nanostructure in water and PBS buffer was studied by goniometry. Electrospun fibers permeability and swelling capacity were assessed, and a dissolution test was performed. In vitro biological tests were realized to investigate the biological compatibility and antimicrobial activity. We obtained flexible matrices that were each approximately 1.0 g in weight. The electrospun fibers were shown to be semipermeable, with water vapor transmission and swelling indexes compatible with the proposed objective. The hydrophilicity was moderate. Matrices containing pure drug modulated drug release adequately during 24 h but presented a high hemolytic index. Complexation promoted a decrease in the hemolytic index and in the drug release but did not negatively impact antimicrobial activity. The drug was released predominantly by diffusion. These results indicate that electrospun PCL matrices containing ß-cyclodextrin/silver sulfadiazine inclusion complexes are a promising pharmaceutical dosage form for wound healing.

Association of Alpha Tocopherol and Ag Sulfadiazine Chitosan Oleate Nanocarriers in Bioactive Dressings Supporting Platelet Lysate Application to Skin Wounds.

Chitosan oleate was previously proposed to encapsulate in nanocarriers some poorly soluble molecules aimed to wound therapy, such as the anti-infective silver sulfadiazine, and the antioxidant α tocopherol. Because nanocarriers need a suitable formulation to be administered to wounds, in the present paper, these previously developed nanocarriers were loaded into freeze dried dressings based on chitosan glutamate. These were proposed as bioactive dressings aimed to support the application to wounds of platelet lysate, a hemoderivative rich in growth factors. The dressings were characterized for hydration capacity, morphological aspect, and rheological and mechanical behavior. Although chitosan oleate nanocarriers clearly decreased the mechanical properties of dressings, these remained compatible with handling and application to wounds. Preliminary studies in vitro on fibroblast cell cultures demonstrated good compatibility of platelet lysate with nanocarriers and bioactive dressings. An in vivo study on a murine wound model showed an accelerating wound healing effect for the bioactive dressing and its suitability as support of the platelet lysate application to wounds.

Nanosuspension-Based Aloe vera Gel of Silver Sulfadiazine with Improved Wound Healing Activity.

The present study focuses on the development and characterization of nanosuspension of a poorly soluble drug, silver sulfadiazine (SSD) incorporated in Aloe vera gel (AV-gel) for improving its therapeutic efficacy. The SSD solution in ammonia was subjected to nanoprecipitation in surfactant solution and particle size was optimized by varying concentration of surfactant. Optimized formulation constituted of 5.5% (w/v) Span 20 and 5.5% (w/v) Tween 80 as a dispersing agent and 0.5% (w/v) Poloxamer 188 as a co-surfactant. The prepared nanosuspension was evaluated for particle size, polydispersity index, surface morphology, and x-ray diffraction study. The optimized nanosuspension was incorporated into nanogel formulation with the addition of 1% AV-gel and 0.5% Carbopol 940 for topical delivery of nanosized SSD. Evaluation of in vitro drug release exhibited a significant enhancement in release rate of the drug from developed nanogel formulation (77.16 ± 3.241%) in comparison to marketed formulation (42.81 ± 1.452%) after 48 h. In vivo histopathological studies in rats for 14 days of application of prepared nanogel showed improvement in the wound healing potential as compared to marketed formulation.

Silver sulfadiazine immobilized glass as antimicrobial fillers for dental restorative materials.

Bacterial colonization and biofilm formation on dental resin composites cause secondary caries that shortens the service life of dental restorative materials. In this study, commercial barium borosilicate based glass powders, fillers widely used in dental composites, were covalently immobilized with silver sulfadiazine to provide antimicrobial effects. The chemical reactions were followed by FT-IR study, elemental analysis, and energy dispersive spectroscopy (EDS), and the reaction pathway was confirmed by model compound studies. The resulting glass powders demonstrated potent antimicrobial effects against Streptococcus mutans (S. mutans). BisGMA (2,2-bis[4-(2-hydroxy-3-methacrylyloxypropoxy)phenyl] propane)-based dental resins containing 2% to 10% of the new silver sulfadiazine glass powders exhibited powerful and durable antimicrobial efficacy against S. mutans. The mechanical properties of the antimicrobial resins were not negatively affected by the silver sulfadiazine glass powders, making them attractive candidates as antimicrobial fillers for dental composites and other related biomedical applications.

Assessment of Deep Partial Thickness Burn Treatment with Keratin Biomaterial Hydrogels in a Swine Model.

Partial thickness burns can advance to full thickness after initial injury due to inadequate tissue perfusion and increased production of inflammatory cytokines, which has been referred to as burn wound progression. In previous work, we demonstrated that a keratin biomaterial hydrogel appeared to reduce burn wound progression. In the present study, we tested the hypothesis that a modified keratin hydrogel could reduce burn wound progression and speed healing. Standardized burn wounds were created in Yorkshire swine and treated within 30 minutes with keratin hydrogel (modified and unmodified), collagen hydrogel, or silver sulfadiazine (SSD). Digital images of each wound were taken for area measurements immediately prior to cleaning and dressing changes. Wound tissue was collected and assessed histologically at several time points. Wound area showed a significant difference between hydrogels and SSD groups, and rates of reepithelialization at early time points showed an increase when keratin treatment was used compared to both collagen and SSD. A linear regression model predicted a time to wound closure of approximately 25 days for keratin hydrogel while SSD treatment required 35 days. There appeared to be no measurable differences between the modified and unmodified formulations of keratin hydrogels.

Evaluation of genipin-crosslinked chitosan hydrogels as a potential carrier for silver sulfadiazine nanocrystals.

In the present study genipin crosslinked chitosan (CHI) hydrogels, which had been constructed and reported in our previous studies (Gao et al., 2014 [22]), were further evaluated for their advantage as a carrier for silver sulfadiazine (AgSD) nanocrystal systems. Firstly, AgSD nanocrystals with a mean particle size of 289nm were prepared by wet milling method and encapsulated into genipin crosslinked CHI hydrogels. AgSD nanocrystals displayed a uniform distribution and very good physical stability in the hydrogel network. Swelling-dependent release pattern was found for AgSD nanocrystals from hydrogels and the release profile could be well fitted with Peppas equation. When AgSD nanocrystals were encapsulated in hydrogels their fibroblast cytotoxicity decreased markedly, and their antibacterial effects against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were still comparable to unencapsulated AgSD nanocrystals. In vivo evaluation in excision and burn cutaneous wound models in mice showed that AgSD nanocrystal hydrogels markedly decreased the expression of inflammatory cytokine IL-6, but increased the levels of growth factors VEGF-A and TGF-ß1. Histopathologically, the wounds treated by hydrogels containing AgSD nanocrystals showed the best healing state compared with commercial AgSD cream, hydrogels containing AgSD bulk powders and blank hydrogels. The wounds treated by AgSD nanocrystal hydrogels were dominated by marked fibroblast proliferation, new blood vessels and thick regenerated epithelial layer. Sirius Red staining assay indicated that AgSD nanocrystal hydrogels resulted in more collagen deposition characterized by a large proportion of type I fibers. Our study suggested that genipin-crosslinked CHI hydrogel was a potential carrier for local antibacterial nanomedicines.

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).