Silk sericin intake leads to increases in L-serine and L-tyrosine levels in the mouse brain and the simultaneous facilitation of brain noradrenergic turnover.

Sericin is a protein component of the silkworm cocoon, and contains a high proportion of L-serine, but it has been mostly disposed of as an industrial waste. However, recent studies have revealed its unique biological functionalities beneficial to human health. This study aimed to evaluate the effect of acute oral intake of sericin on amino acid and neurotransmitter metabolism in the mouse brain. Acute administration of chemically modified sericin (0.26 g/30 g body weight) increased L-serine and L-tyrosine levels in the serum and brain, although the L-tyrosine content in the sericin was less than 3% (w/w). In addition, sericin administration led to a significant facilitation of noradrenergic turnover via enhancement of 3-methoxy-4-hydroxyphenylethyleneglycol, a principal metabolite of noradrenaline, in several of the brain regions examined. These present findings suggest that oral intake of sericin efficiently delivers L-serine and L-tyrosine to the brain, thus stimulating noradrenergic activity in the brain.Abbreviations: DA: dopamine; 5-HIAA: 5-hydroxyindoleicetic acid; 5-HT: 5-hydroxytryptamine; HVA: homovanillic acid; MHPG: 3-methoxy-4-hydroxyphenylethyleneglycol; 3-MT: 3-methoxytyramine; NA: noradrenaline; NM: normetanephrine; Veh: vehicle.

Augmented Therapeutic Efficacy of Naringenin Through Microemulsion-Loaded Sericin Gel Against UVB-Induced Photoaging.

Naringenin (NAR) is a flavonoid found in citrus fruits such as grapes and oranges. Recently, NAR has demonstrated its potential in inhibition of photoaging. The aim of the present study was to investigate the efficacy of sericin (SR) gel loaded with NAR microemulsion (ME) to inhibit UVB-induced photoaging and prevention of epidermoid carcinoma in animal model. NAR -ME was prepared and optimized through Box-Behnken design. The optimized ME was loaded into sericin (SR) gel. The formulations were subjected to various in vitro, in vivo and cytotoxicity studies over A431 cell lines. The optimized ME revealed a globule size of 249.05 ± 3.78 nm, 6.7 ± 0.5 pH and 73.1 ± 2.11% release over a period of 24 h respectively. Cytotoxicity studies revealed a depression in IC50 value in NAR -ME (65.11 ± 1.54 µg/ml) when compared with NAR (118.1 ± 2.09 µg/ml). The NAR-ME-SR gel displayed enhanced therapeutic potential when compared with plain NAR, in terms of augmented antiproliferative activity. Graphical abstract.

Instillation of Sericin Enhances Corneal Wound Healing through the ERK Pathway in Rat Debrided Corneal Epithelium.

Sericin is a major constituent of silk produced by silkworms. We previously found that the instillation of sericin enhanced the proliferation of corneal epithelial cells, and acted to promote corneal wound healing in both normal and diabetic model rats. However, the mechanisms by which sericin promotes the proliferation of corneal cells have not been established. In this study, we investigated the effects of sericin on Akt and ERK activation in a human corneal epithelial cell line (HCE-T cells) and rat debrided corneal epithelium. Although Akt phosphorylation was not detected following the treatment of HCE-T cells with sericin, ERK1/2 phosphorylation was enhanced. The growth of HCE-T cells treated with sericin was significantly increased, with the cell growth of sericin-treated HCE-T cells being 1.7-fold higher in comparison with vehicle-treated HCE-T cells. On the other hand, both of an ERK inhibitor U0126 (non-specific specific inhibitor) and SCH772984 (specific inhibitor) attenuated the enhanced cell growth by sericin, and the growth level in the case of co-treatment with sericin and ERK1/2 inhibitor was similar to that of cells treated with ERK1/2 inhibitor alone. In an in vivo study using rat debrided corneal epithelium, the corneal wound healing rate was enhanced by the instillation of sericin, and this enhancement was also attenuated by the instillation of U0126. In addition, the corneal wound healing rate in rats co-instilled with sericin and U0126 was similar to that following the instillation of U0126 alone. In conclusion, we found that the instillation of sericin enhanced cell proliferation via the activation of the MAPK/ERK pathway, resulting in the promotion of corneal wound healing in rat eyes. These findings provide significant information for designing further studies to develop potent corneal wound-healing drugs.

Combination Ointment Containing Solid Tranilast Nanoparticles and Dissolved Sericin Is Efficacious for Treating Skin Wound-Healing Deficits and Redness in Diabetic Rats.

We attempted to design a combination ointment containing solid tranilast nanoparticles and dissolved sericin as a wound-healing drug (TS-combination ointment), and evaluated its usefulness as therapy for wound-healing deficits in streptozotocin-induced diabetic rat (STZ rat) using kinetic analyses as an index. Solid tranilast nanoparticles were prepared by bead mill methods with low-substituted methylcellulose; the mean particle size of the tranilast nanoparticles was 70 nm. The ointment was designed to contain the tranilast nanoparticles plus sericin powder and/or Carbopol® 934. Skin wound healing in STZ rats begins significantly later than in normal rats. Although the skin wound healing rate in STZ rats treated with an ointment containing tranilast nanoparticles was lower than in STZ rats treated with vehicle, the ointment was effective in reducing redness. An ointment containing sericin enhanced the skin-healing rate, but the preventive effect on redness was weak. On the other hand, the combination of tranilast and sericin increased both the skin healing rate and reduction in redness. In conclusion, we have adapted kinetic analyses to skin wound healing in rats, and found these analyses to be useful as an index of wound healing ability by a wound-healing drug. In addition, we show that treatment with the TS-combination ointment enhances the skin wound healing rate and reduces redness. These findings provide information significant to the search for new wound-healing therapies and for the design of wound-healing drugs.

Intra-articular Retention and Anti-arthritic Effects in Collagen-Induced Arthritis Model Mice by Injectable Small Interfering RNA Containing Hydrogel.

Small interfering RNAs (siRNAs) are expected to offer a means of treating rheumatoid arthritis (RA) because they allow the specific silencing of genes related to RA pathogenesis. In our previous study, we reported that the siRNA targeted against RelA (anti-RelA siRNA), an important nuclear factor-kappaB (NF-κB) subdomain, was an effective therapeutic in atopic dermatitis and RA model animals. In this study, to develop an intra-articular injectable gel formulation against RA, we prepared a hydrogel that contains anti-RelA siRNA, and determined the in vitro release profile (%) and in vivo intra-articular retention of fluorescence-labeled model siRNA, and the anti-arthritic effects of the anti-RelA siRelA containing hydrogel in RA model mice. We selected the silk protein, sericin (SC), as an aqueous gel base, as it is a biocompatible and useful for forming hydrogels without a cross-linker. We showed that fluorescence-labeled model siRNA was continuously released from SC hydrogel in vitro, and retained in the knee joint of rats after injection of siRNA hydrogel. In addition, the knee joint thickness, clinical severity and incidence (%) in collagen-induced arthritis (CIA) mice as RA model treated with anti-RelA siRNA containing hydrogel were more improved than untreated, anti-RelA siRNA solution and negative control siRNA containing hydrogel group. Therefore, the intra-articular injectable sericin hydrogel formulation containing of anti-RelA siRNA could be a great potential therapeutic in rheumatoid arthritis.

Can Sericin Prove Useful as a Pleurodesis Agent or Tissue Glue?

Background Sericin is a natural, gum-like, macromolecule protein, synthesized from silkworms for the formation of cocoon shells. The aim of the present study is to describe the effects of sericin when used for pleurodesis and/or as tissue glue. Methods Adult, male, 12-week-old Wistar albino rats, weighing 257 to 395 g were used in the present study (n = 12). The animals were randomly divided into two equal groups as the sericin and the control group. After intramuscular administration of the anesthetic agent, the rats were intubated and mechanically ventilated. A left thoracotomy was performed and 30 mg sericin powder was instilled into the thoraxes of the sericin group. The remaining rats were allocated to a sham thoracotomy group. The animals were housed in individual cages, fed ad-libitum, and sacrificed 8 days after. After sacrifice, the left hemithoraxes were removed en bloc and underwent histopathologic examination. Results Masson trichrome staining was applied on the visceral pleura sections of all the animals. Each animal specimen (n = 6, 100%) in the control group showed minimal collagen deposition, while only one rat (16.67%) in the sericin group had minimal collagen deposition. However, in the sericin group, five animals (83.33%) showed dense collagen deposition, fibroblastic activity, and fibrosis. According to the test method, independent t-test, developing fibroblastic activity and fibrosis are statistically significant between the two groups (p < 0.01). There were no foreign-body reactions and no evidence of biological glue on the specimens in the sericin group. The rats in the sericin group had lower inflammatory reactions compared with those in the control group. Emphysema was observed in two rats (33.33%) in the sericin group and in four rats (66.67%) in the control group. Therefore, sericin was found to be associated with an increase in fibroblastic activity and fibrosis in visceral pleura without exerting any adverse effect on the lung parenchyma. Conclusion Sericin is a new and researchable protein for chest diseases and thoracic surgery. To develop an effect of dense collagen deposition, fibroblastic activity, and fibrosis in the visceral pleura, without significant adverse effects, is remarkable. Therefore, sericin may be useful as a pleurodesis agent or natural biological glue in the future. Sericin treatment can add value to the disciplines of pulmonology and thoracic surgery.

The development of non-toxic ionic-crosslinked chitosan-based microspheres as carriers for the controlled release of silk sericin.

Silk sericin is recently shown to possess various biological activities for biomedical applications. While various sericin carriers were developed for drug delivery system, very few researches considered sericin as a bioactive molecule itself. In this study, sericin incorporated in the chitosan-based microspheres was introduced as a bioactive molecule and bioactive carrier at the same time. The chitosan/sericin (CH/SS) microspheres at different composition (80/20, 70/30, 60/40, and 50/50) were successfully fabricated using anhydroustri-polyphosphate (TPP) as a polyanionic crosslinker. The microspheres with an average size of 1-4 µm and narrow size distribution were obtained. From FT-IR spectra, the presence of both chitosan and sericin in the microspheres confirmed the occurrence of ionic interaction that crosslink them within the microspheres. We also found that the CH/SS microspheres prepared at 50/50 could encapsulate sericin at the highest percentage (37.28%) and release sericin in the most sustained behavior, possibly due to the strong ionic interaction of the positively charged chitosan and the negatively charged sericin. On the other hand, the composition of CH/SS had no effect on the degradation rate of microspheres. All microspheres continuously degraded and remained around 20% after 14 days of enzymatic degradation. This explained that the ionic crosslinkings between chitosan and sericin could be demolished by the enzyme and hydrolysis. Furthermore, we have verified that all CH/SS microspheres at any concentrations showed non-toxicity to L929 mouse fibroblast cells. Therefore, we suggested that the non-toxic ionic-crosslinked CH/SS microspheres could be incorporated in wound dressing material to achieve the sustained release of sericin for accelerated wound healing.

Randomized, double-blinded, vehicle-controlled, split-face study to evaluate the effects of topical application of a Gold Silk Sericin/Niacinamide/Signaline complex on biophysical parameters related to skin ageing.

OBJECTIVE: To investigate the effects of topical application of a Gold Silk Sericin (GSS) complex on biophysical parameters related to skin ageing. METHODS: A range of non-invasive bioengineering methods were deployed in an 8-week randomized, double-blinded, vehicle-controlled, split-face study among 40 female subjects aged 40-70. Endpoints measured included expert grades of skin condition, stratum corneum (SC) hydration, SC barrier function, elasticity and surface topography. RESULTS: The GSS complex produced significant single-variable (P < 0.05) improvements in SC hydration, barrier function, elasticity and surface topography compared with the Vehicle control. CONCLUSION: The GSS complex examined in this study represents an interesting new cosmetic topical technology with which to address multiple aspects of aged/photoaged female facial skin.

Accelerated healing of full-thickness wounds by genipin-crosslinked silk sericin/PVA scaffolds.

Silk sericin has recently been studied for its advantageous biological properties, including its ability to promote wound healing. This study developed a delivery system to accelerate the healing of full-thickness wounds. Three-dimensional scaffolds were fabricated from poly(vinyl alcohol) (PVA), glycerin (as a plasticizer) and genipin (as a crosslinking agent), with or without sericin. The physical and biological properties of the genipin-crosslinked sericin/PVA scaffolds were investigated and compared with those of scaffolds without sericin. The genipin-crosslinked sericin/PVA scaffolds exhibited a higher compressive modulus and greater swelling in water than the scaffolds without sericin. Sericin also exhibited controlled release from the scaffolds. The genipin-crosslinked sericin/PVA scaffolds promoted the attachment and proliferation of L929 mouse fibroblasts. After application to full-thickness rat wounds, the wounds treated with genipin-crosslinked sericin/PVA scaffolds showed a significantly greater reduction in wound size, collagen formation and epithelialization compared with the control scaffolds without sericin but lower numbers of macrophages and multinucleated giant cells. These results indicate that the delivery of sericin from the novel genipin-crosslinked scaffolds efficiently healed the wound. Therefore, these genipin-crosslinked sericin/PVA scaffolds represent a promising candidate for the accelerated healing of full-thickness wounds.

Dietary silk protein, sericin, improves epidermal hydration with increased levels of filaggrins and free amino acids in NC/Nga mice.

Epidermal hydration is maintained primarily by natural moisturising factors (NMF), of which free amino acids (AA) are major constituents that are generated by filaggrin degradation. To identify dietary sources that may improve skin dryness of atopic dermatitis (AD), we investigated dietary effects of silk proteins, sericin and fibroin, on epidermal levels of hydration, filaggrins and free AA, as well as PPARγ, peptidylarginine deiminase-3 (PAD3) and caspase-14 proteins involved in filaggrin expression and degradation processes. NC/Nga mice, an animal model of AD, were fed a control diet (group CA: atopic control) or diets with 1 % sericin (group S) or fibroin (group F) for 10 weeks. In group S, epidermal levels of hydration, total filaggrins and total free AA, as well as PPARγ, PAD3 and caspase-14, which were reduced in group CA, were increased to higher or similar levels of a normal control group of BALB/c mice (group C). Furthermore, profilaggrin, a precursor with multiple filaggrin repeats, and three repeat intermediates were increased, while two repeat intermediates and filaggrin were decreased in parallel with increased levels of glutamate and serine, major AA of NMF in group S. Despite increased levels of total filaggrins, total free AA, PPARγ and PAD3, epidermal levels of hydration, glutamate, serine and caspase-14 were not increased, but other minor AA of NMF were highly detected in group F. Dietary sericin improves epidermal hydration in parallel with enhancing profilaggrin expression and degradation into free AA that is coupled with elevated levels of PPARγ, PAD3 and caspase-14 proteins.

Sericin cream reduces pruritus in hemodialysis patients: a randomized, double-blind, placebo-controlled experimental study.

BACKGROUND: Uremic pruritus (UP) is a significant complication in ESRD patients and substantially impairs their quality of life. UP is considered to be a skin manifestation of chronic inflammation. Because sericin can suppress the release of pro-inflammatory cytokines, the purpose of this study was to investigate the short-term safety and efficacy of sericin cream for treating UP in hemodialysis patients. METHODS: This study used a double-blind design to investigate the effects of random topical administration of sericin cream and cream base (placebo) on either the right or left extremities of hemodialysis patients for 6 weeks. Skin hydration, irritation and pigmentation were evaluated every 2 weeks using Skin Diagnostic SD27. The visual analog scale for itching was also evaluated every 2 weeks, and the Kidney Disease Quality of Life Short Form was performed on the day of each patient's enrollment and after 6 weeks of treatment. RESULTS: Fifty dialysis patients were enrolled, 47 of which completed the study. The hydration of the skin of the patients' extremities increased significantly after administration of sericin cream; significant differences were found between sericin treatment and control after 6 weeks of treatment (p = 0.041 for arms and p = 0.022 for legs, respectively). Moreover, a significant difference was also found in skin irritation between the two treatments (p = 0.013 for arms and p = 0.027 for legs, respectively). At the end of the study, the skin pigmentation level was significantly reduced on both the arms (p = 0.032) and legs (p = 0.021) of the sericin-treated side compared with the side treated with cream base. The mean itching score decreased significantly from moderate to severe at the time of enrollment to mild pruritus after 6 weeks of treatment (p = 0.002). A better quality of life was found in all domains tested although statistically significant differences before and after treatment was found only in the patients' pain scores, the effect of kidney disease on daily life, sleep quality and symptoms or problems related to kidney disease. CONCLUSIONS: We conclude that sericin cream has a high potential for reducing UP in hemodialysis patients.The trial registration number of this study is ISRCTN16019033; its public title is "sericin cream reduces pruritus in hemodialysis patients".

Consumption of a resistant protein, sericin, elevates fecal immunoglobulin A, mucins, and cecal organic acids in rats fed a high-fat diet.

We previously reported that consumption of a resistant protein, sericin, reduces colon tumorigenesis, constipation, and serum TG in rodents. The present study was conducted to elucidate the effects of dietary sericin on the intestinal luminal environment in rats fed a high-fat (HF) diet. Rats were fed 300 or 50 g/kg of beef tallow with or without 40 g/kg sericin, a protein purified from cocoons of Bombix mori, for 3 wk. Intestinal luminal variables, including IgA (index of intestinal immune function), mucins (index of barrier function), organic acids, microflora, and secondary bile acids, were measured. Dietary sericin markedly elevated fecal IgA in the HF diet group (3-fold, P < 0.05) but not in the low-fat (LF) diet group. Fecal mucin levels were elevated by sericin intake in the HF diet group (P < 0.05). Cecal organic acids, including acetate, propionate, n-butyrate, and succinate, were significantly lower in the HF diet group compared with the LF diet group. Dietary sericin significantly elevated cecal acetate and n-butyrate in the HF diet group but not in the LF diet group. Compared with the LF diet, the HF diet significantly increased serum TG in the untreated group but not in those fed sericin. The HF diet increased lower density lipoprotein (VLDL + IDL + LDL) cholesterol and it was reduced by sericin intake (P < 0.05). There was an inverse correlation between serum TG and cecal acetate (Spearman rank correlation coefficient = -0.63; P < 0.001). The profile of microflora in cecal digesta and fecal secondary bile acids (a risk factor for colon cancer) did not differ between the HF diet and HF diet with sericin groups. These results suggest a novel and favorable effect of sericin on colon health by modulating intestinal immune and barrier functions and fermentation in rats fed a HF diet.

Consumption of sericin reduces serum lipids, ameliorates glucose tolerance and elevates serum adiponectin in rats fed a high-fat diet.

The effect was examined of dietary sericin on the lipid and carbohydrate metabolism in rats fed with a high-fat diet. The rats were fed with a 20% beef tallow diet with or without sericin at the level of 4% for 5 weeks. The final body weight and white adipose tissue weight were unaffected by dietary manipulation. The consumption of sericin significantly reduced the serum levels of triglyceride, cholesterol, phospholipids and free fatty acids. Serum very-low-density lipoprotein (VLDL)-triglyceride, VLDL-cholesterol, low-density lipoprotein (LDL)-cholesterol and LDL-phospholipids were also significantly reduced by the sericin intake. Liver triglyceride and the activities of glucose 6-phosphate dehydrogenase and malic enzyme, the lipogenic enzymes, were also reduced by the sericin intake. Dietary sericin caused a marked elevation in serum adiponectin. The consumption of sericin suppressed the increases in plasma glucose and insulin levels after an intraperitoneal glucose injection. These results imply the usefulness of sericin for improving the lipid and carbohydrate metabolism in rats fed on a high-fat diet.

Safety Assessment of Water-Extract Sericin from Silkworm (Bombyx mori) Cocoons Using Different Model Approaches.

Sericin is a natural protein component of silks of silkworm and has potential utility in multiple areas such as pharmacological, cosmetics, and biotechnological industries. However, the understanding of its toxicological safety is still limited. This study evaluated the safety of water-extract sericin from silkworm (Bombyx mori) cocoons using different model approaches, including three genotoxicity studies (the bacterial reverse mutation test, the mammalian erythrocyte micronucleus test, and the mouse spermatogonia chromosomal aberration test) and a 90-day subchronic toxicity study in Sprague-Dawley (SD) rats. The results of this study showed that water-extract sericin was nonmutagenic and nongenotoxic both in vitro and in vivo. Sericin did not induce significant changes in the body and organ weight, food intake, blood hematology and serum biochemistry, urine index, and histopathology in rats. The NOAEL of sericin was determined to be 1 g/kg/day for male and female rats. These results indicated that water-extract sericin was of low toxicity in the experimental conditions of the current study and had the potential for application in food-related products.

Hydrophobic IR780 loaded sericin nanomicelles for phototherapy with enhanced antitumor efficiency.

The near-infrared dye, IR780 iodide, has been utilized in photodynamic therapy (PDT) and photothermal therapy (PTT). However, the hydrophobicity and photosensitivity of IR780 limit its further applications in biomedical fields. Herein, the hydrophilic sericin was modified with hydrophobic cholesterol to form an amphiphilic macromolecular conjugate (Ser-Chol). The tumor-targeting agent, folic acid (FA), was further linked to the conjugate (FA-Ser-Chol). The IR780 could be encapsulated into such amphiphilic macromolecule to form stable micelles (FA-Ser-Chol/IR780) by self-assembly, and the solubility and photo-stability of IR780 were greatly improved. The FA-Ser-Chol/IR780 micelles could be efficiently absorbed by FA-positive gastric cancer cells (BGC-823) through FA receptors, while the uptake micelles showed remarkable PDT and PTT cytotoxicity towards BGC-823 cells under laser irradiation of 808 nm. Therefore, FA-Ser-Chol micelles may serve as a promising IR780 carrier for PDT and PTT therapy.

The wound healing and antibacterial potential of triple-component nanocomposite (chitosan-silver-sericin) films loaded with moxifloxacin.

AIM: The current study reports the development and evaluation of chitosan-sericin-silver nanocomposite (CSSN) films without and with moxifloxacin (Mox). METHODOLOGY: The film preparation method involved the in-situ synthesis of silver nanoparticles within the chitosan-sericin colloidal composite followed by preparation into a film by solvent casting technique. In-situ formation and the particle size analysis of the silver nanoparticles was performed via UV-Visible and zeta-size spectrometer. The prepared films were tested for swelling ratio, contents uniformity, in-vitro Mox release, and permeation analysis. The morphological (SEM), elemental (EDX), spectral (FT-IR), structural (XRD), and thermal (TGA and DSC) properties of the composites were also inspected. The antibacterial activity of the CSSN films was performed against seven pathogenic bacterial strains including five ATCC and two clinical strains. The potential wound healing activity of the composite films was evaluated on burn wound model induced in Sprague Dawley male rats. RESULTS: The prepared films displayed good swelling profile with a sustained in-vitro Mox release and permeation profile; attaining maximum of 78.57% (CSSM3) release and 55.05% (CSSM1) permeation (CSSM1) in 24 h. The prepared films, particularly the Mox-loaded CSSN films displayed a promising antibacterial activity against all the tested strains with the activity being highest against MRSA (clinical isolates). The prepared films indicated a remarkable wound healing applications with successful fibrosis, collagen reorganization, neovascularization, and mild epidermal regeneration after 7 days of treatment with no silver ions detection in animal's blood. CONCLUSION: The obtained findings strongly suggest the use of the prepared novel composite dressing for wound care applications.

Consumption of sericin suppresses colon oxidative stress and aberrant crypt foci in 1,2-dimethylhydrazine-treated rats by colon undigested sericin.

This study was conducted to examine the mechanisms of the anti-colon tumor effect of dietary sericin. Dietary supplementation of 3% sericin reduced colon mucosal lipid peroxide and aberrant crypt foci in 1,2-dimethylhydrazine-treated rats. The colon content from sericin-fed rats had much stronger antioxidant activity compared to that from control rats not receiving sericin. The amino acid composition of undigested proteins in the colon contents from sericin-fed rats was similar to that of sericin ingested. The results suggest that the strong antioxidant activity of undigested sericin in the colon content causes lower oxidative stress and tumorigenesis in the colon.

Towards understanding the distribution and tumor targeting of sericin regulated spherical calcium phosphate nanoparticles.

The study of calcium phosphate (CaP) nanoparticles in vivo is still incomplete, which has limited their applications for biomedical delivery. Herein, we synthesized amorphous spherical calcium phosphate (S-CaP) nanoparticles with an average size of 80 nm via a co-precipitation method in the presence of silk sericin as the regulation template. S-CaP was labeled by the near-infrared dye reagent DiR, and then, the labeled nanoparticles (S-CaP@DiR) were used to investigate the distribution and degradation in healthy mice by IVIS and TEM. The results showed that the S-CaP nanoparticles were mainly distributed in the liver, and ∼90% of them (500 µg) could be degraded by the liver within 2 weeks. Tumor-bearing mice were then prepared, and the S-CaP was injected intravenously. Strikingly, the nanoparticles can effectively target solid tumors in cancer cell-bearing mice, indicating that the solid tumor was a foundation for the enrichment of the nanoparticles by the EPR effect, which showed the important potential of biodegradable inorganic nanoparticles in clinical drugs for tumor therapy.

Wound healing applications of sericin/chitosan-capped silver nanoparticles incorporated hydrogel.

Microbial contamination in wounds leading to severe sepsis can be treated by silver-based antiseptics. However, frequent application of silver-based antiseptics, staining of skin, burning, and irritation at application site resulted to poor patient compliances. Thus, we formulated sericin- and chitosan-capped silver nanoparticle (S/C-SNP)-loaded hydrogel for accelerated wound healing and antimicrobial properties. The wound healing property of sericin, antibacterial nature of chitosan and silver, and mucoadhesive property of carbopol were utilized in development of novel wound dressing hydrogel to investigate the combined effect of these materials for effective treatment of wounds. The chemical reduction method was successfully employed for the synthesis of SNPs using sericin and chitosan as a capping/reducing agent. The SNPs were characterized by ultraviolet-spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The optimized SNPs were further used for preparation of carbopol hydrogel (0.5, 0.75, and 1.0 % w/v). The prepared hydrogels were characterized for pH, viscosity, and texture analysis. The antimicrobial activity and wound healing activity of the optimized hydrogel (S/C-SNPs G-1) demonstrated higher bactericidal activity and wound closure, as supported by results of histopathology. Hydrogel containing capped SNPs has application in wound healing treatment.

Controlled Release of Chitosan and Sericin from the Microspheres-Embedded Wound Dressing for the Prolonged Anti-microbial and Wound Healing Efficacy.

One approach in wound dressing development is to incorporate active molecules or drugs in the dressing. In order to reduce the frequency of dressing changes as well as to prolong wound healing efficacy, wound dressings that can sustain the release of the active molecules should be developed. In our previous work, we developed chitosan/sericin (CH/SS) microspheres that released sericin in a controlled rate. However, the difficulty of applying the microspheres that easily diffuse and quickly degrade onto the wound was its limitations. In this study, we aimed to develop wound dressing materials which are easier to apply and to provide extended release of sericin. Different amounts of CH/SS microspheres were embedded into various compositions of polyvinyl alcohol/gelatin (PVA/G) scaffolds and fabricated using freeze-drying and glutaraldehyde crosslinking techniques. The obtained CH/SS microspheres-embedded scaffolds with appropriate design and formulation were introduced as a wound dressing material. Sericin was released from the microspheres and the scaffolds in a sustained manner. Furthermore, an optimized formation of the microspheres-embedded scaffolds (2PVA2G+2CHSS) was shown to possess an effective antimicrobial activity against both gram-positive and gram-negative bacteria. These microspheres-embedded scaffolds were not toxic to L929 mouse fibroblast cells, and they did not irritate the tissue when applied to the wound. Finally, probably by the sustained release of sericin, these microspheres-embedded scaffolds could promote wound healing as well as or slightly better than a clinically used wound dressing (Allevyn®) in a mouse model. The antimicrobial CH/SS microspheres-embedded PVA/G scaffolds with sustained release of sericin would appear to be a promising candidate for wound dressing application.