Levofloxacin loaded poly (ethylene oxide)-chitosan/quercetin loaded poly (D,L-lactide-co-glycolide) core-shell electrospun nanofibers for burn wound healing.

This study developed a new burn wound dressing based on core-shell nanofibers that co-deliver antibiotic and antioxidant drugs. For this purpose, poly(ethylene oxide) (PEO)-chitosan (CS)/poly(D,L-lactide-co-glycolide) (PLGA) core-shell nanofibers were fabricated through co-axial electrospinning technique. Antibiotic levofloxacin (LEV) and antioxidant quercetin (QS) were incorporated into the core and shell parts of PEO-CS/PLGA nanofibers, respectively. The drugs could bond to the polymer chains through hydrogen bonding, leading to their steady release for 168 h. An in vitro drug release study showed a burst effect followed by sustained release of LEV and QS from the nanofibers due to the Fickian diffusion. The NIH 3T3 fibroblast cell viability of the drug loaded core-shell nanofibers was comparable to that in the control (tissue culture polystyrene) implying biocompatibility of the nanofibers and their cell supportive role. However, there was no significant difference in cell viability between the drug loaded and drug free core-shell nanofibers. According to in vivo experiments, PEO-CS-LEV/PLGA-QS core-shell nanofibers could accelerate the healing process of a burn wound compared to a sterile gauze. Thanks to the synergistic therapeutic effect of LEV and QS, a significantly higher wound closure rate was recorded for the drug loaded core-shell nanofibrous dressing than the drug free nanofibers and control. Conclusively, PEO-CS-LEV/PLGA-QS core-shell nanofibers were shown to be a promising wound healing material that could drive the healing cascade through local co-delivery of LEV and QS to burn wounds.

Thermoresponsive in situ forming and self-healing double-network hydrogels as injectable dressings for silymarin/levofloxacin delivery for treatment of third-degree burn wounds.

Our study aimed to introduce a novel double-cross-linked and thermoresponsive hydrogel with remarkable potential for accelerating third-degree burn wound healing. Burn injuries are recognized as challenging, critical wounds. Especially in third-degree burns, treatment is demanding due to extended wounds, irregular shapes, significant exudation, and intense pain during dressing changes. In this work, hydrogels made of zwitterionic chitosan and dialdehyde starch (ZCS and ZDAS) were created to deliver silymarine (SM) and levofloxacin (LEV). The hydrogels were effortlessly produced using dynamic Schiff base linkages and ionic interactions between ZCS and ZDAS at appropriate times. The pore uniformity, gel fraction, and commendable swelling properties can imply a suitable degree of Schiff base cross-link. The hydrogel demonstrated outstanding shape retention, and significant self-healing and flexibility abilities, enabling it to uphold its form even during bodily movements. After injecting biocompatible hydrogel on the wound, a notable acceleration in wound closure was observed on day 21 (98.1 ± 1.10 %) compared to the control group (75.1 ± 6.13 %), and histopathological analysis revealed a reduction of inflammation that can be linked to remarkable antioxidant and antibiotic properties. The results demonstrate the hydrogel's efficacy in promoting burn wound healing, making it a promising candidate for medical applications.

Novel polyurethane-based ionene nanoparticles electrostatically stabilized with hyaluronic acid for effective gene therapy.

Gene therapy is considered to be a valuable strategy for effective cancer treatment. However, the development of effective delivery systems that can specifically deliver gene materials, such as siRNA to tumor tissues plays a critical role in cancer therapy. In the present study, we have developed a novel complex that is based on an electrostatic interaction between cationic polyurethane ionene (CPUI) nanoparticles and an anti-signal transducer and activator of transcription 3 (STAT3) siRNA. For active targeting, hyaluronic acid (HA) was used to coat the complexes, which significantly reduced the cytotoxicity of the blank nanocarriers while demonstrating high transport efficiency of the siRNA via the CD44-mediated endocytosis pathway in MCF-7 breast cancer cells. The targeted nanocarriers (HA/CPUI/siRNA) showed significantly higher cellular internalization in flow cytometry and confocal microscopy compared with the non-targeted system (CPUI/siRNA). In addition, the incorporation of HA on the surface of the complexes resulted in significantly greater suppression of the STAT3 gene compared to the corresponding non-targeted formulation. Whole-body fluorescence images showed more significant tumor accumulation of the targeted nanocarriers in 4T1 breast tumor-bearing mice. Therefore, HA/CPUI/siRNA nanocarriers are an interesting option for the siRNA-targeted treatment of breast cancer cells.

Targeted pH- and redox-responsive AuS/micelles with low CMC for highly efficient sonodynamic therapy of metastatic breast cancer.

The efficacy of injectable micellar carriers is hindered due to the disassembly of micelles into free surfactants in the body, resulting in their dilution below the critical micelle concentration (CMC). Copolymer micelles were developed to address this issue, containing a superhydrophilic zwitterionic block and a superhydrophobic block with a disulfide bond, which exhibited a CMC lower than conventional micellar carriers. Cleavable copolymers composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) zwitterion and polycaprolactone CHLZW as the shell, with gold nanoparticles as their core, were studied to deliver doxorubicin to tumor cells while reducing the side effect of the free cytotoxic agent. The research focused on the impact of gold nanoparticles present in targeted TMT-micelles core on stability and in vivo bioavailability and sonotoxicity of the nanoparticles, as well as their synergistic effect on targeted chemotherapy. The nanomicelles prepared in this study demonstrated excellent biocompatibility and responsiveness to stimuli. PCL-SS-MPC nanomicelles displayed drug release in response to GSH and pH, resulting in high DOX release at GSH 10 mM and pH 5. Our findings, supported by MTT, flow cytometry, and confocal laser scanning microscopy, demonstrated that AuS-PM-TMTM-DOX micelles effectively induced apoptosis and enhanced cellular uptake in MCF7 and MDA-MB231 cell lines. The cytotoxic effects of AuS-PM-DOX/US on cancer cells were approximately 38 % higher compared to AuS-PM-DOX samples at a concentration of IC50 0.68 nM. This increase in cellular toxicity was primarily attributed to the promotion of apoptosis. The introduction of disulfide linkages in AuSNPs resulted in increased ROS production when exposed to ultrasound stimulation, due to a reduction in GSH levels. Compared to other commercially available nanosensitizers such as titanium dioxide, exposure of AuS-PM to ultrasound radiation (1.0 W/cm, 2 min) significantly enhanced cavitation effects and resulted in 3 to 5 times higher ROS production. Furthermore, laboratory experiments using human breast cancer cells (MDA-MB-231, MCF7) demonstrated that the toxicity of AuS-PM in response to ultrasound waves is dose-dependent. The findings of this study suggest that this formulated nanocarrier holds great potential as a viable treatment option for breast cancer. It can induce apoptosis in cancer cells, reduce tumor size, and display notable therapeutic efficacy.

Botulinum toxin A dissolving microneedles for hyperhidrosis treatment: design, formulation and in vivo evaluation.

Multiple periodic injections of botulinum toxin A (BTX-A) are the standard treatment of hyperhidrosis which causes excessive sweating. However, BTX-A injections can create problems, including incorrect and painful injections, the risk of drug entry into the bloodstream, the need for medical expertise, and waste disposal problems. New drug delivery systems can substantially reduce these problems. Transdermal delivery is an effective alternative to conventional BTX-A injections. However, BTX-A's large molecular size and susceptibility to degradation complicate transdermal delivery. Dissolving microneedle patches (DMNPs) encapsulated with BTX-A (BTX-A/DMNPs) are a promising solution that can penetrate the dermis painlessly and provide localized translocation of BTX-A. In this study, using high-precision 3D laser lithography and subsequent molding, DMNPs were prepared based on a combination of biocompatible polyvinylpyrrolidone and hyaluronic acid polymers to deliver BTX-A with ultra-sharp needle tips of 1.5 ± 0.5 µm. Mechanical, morphological and histological assessments of the prepared DMNPs were performed to optimize their physicochemical properties. Furthermore, the BTX-A release and diffusion kinetics across the skin layers were investigated. A COMSOL simulation was conducted to study the diffusion process. The primary stability analysis reported significant stability for three months. Finally, the functionality of the BTX-A/DMNPs for the suppression of sweat glands was confirmed on the hyperhidrosis mouse footpad, which drastically reduced sweat gland activity. The results demonstrate that these engineered DMNPs can be an effective, painless, inexpensive alternative to hypodermic injections when treating hyperhidrosis.

pH-sensitive bilayer electrospun nanofibers based on ethyl cellulose and Eudragit S-100 as a dual delivery system for treatment of the burn wounds; preparation, characterizations, and in-vitro/in-vivo assessment.

A pH-sensitive bilayer electrospun nanofibrous mat containing both antibiotic (gentamicin sulfate, GEN) and non-steroidal anti-inflammatory (diclofenac sodium, DIC) drugs was fabricated for burn wound dressing by electrospinning technique, in which ethyl cellulose (EC) and ethyl cellulose/Eudragit S-100 (EC/ES-100) formed the top and bottom layers, respectively. The fabricated pH-sensitive bilayer electrospun nanofibrous mats were characterized from aspects of both structure and efficiency. Physicochemical properties were investigated via SEM, FTIR, and TGA. The swelling ratio and in vitro drug release of the fabricated nanofibrous mats were studied in different pHs. MTT was applied to assess the safety of the fiber mats. Finally, the in vivo efficiency of the designed pH-sensitive bilayer electrospun nanofibrous mats was examined on the male Wistar rats. Based on the histological analysis and wound healing test (in vivo animal experiments), the (ES100/EC-DIC/GEN)-(EC) pH-sensitive bilayer nanofibrous mat displayed faster wound healing than other bilayer nanofibrous mat. As a result, (ES100/EC-DIC/GEN)-(EC) bilayer nanofibrous mat with pH-responsion could accelerate the burn wound healing process via decreasing the adverse effects of GEN and DIC as topical antimicrobial and anti-inflammatory agents, receptively.

Waterborne polyurethane magnetic nanomicelles with magnetically governed functions for breast cancer therapy.

Drug delivery strategies aim to maximize a drug's therapeutic efficiency by increasing the drug's concentration at the target site while minimizing delivery to off-target tissues. There is a great deal of interest in using magnetic nanoparticles in combination with applied magnetic fields to selectively control drug accumulation and release in target tissue while minimizing effects on other tissues. In this study, a magnetic targeted drug delivery system based on waterborne polyurethane nanomicelles was prepared by encapsulating hydrophobic doxorubicin (DOX, model drug) and hydrophobic oleic acid-superparamagnetic nanoparticles (SPION-OA) into the hydrophobic core of waterborne polyurethane micelles (CPUM) using the solvent evaporation method. The prepared drug-loaded magnetomicelles (CPUM-DOX-SPION) had a spherical shape with an average diameter of 158 nm. The magnetomicelles showed superparamagnetic properties with excellent magnetic resonance imaging (MRI) contrast effects and T2 relaxation in vitro. In the absence and presence of a magnetic field, the cytocompatibility and cellular uptake of the samples were assessed by MTT assay and flow cytometry, respectively, and the cells were imaged with a confocal microscope. Application of the magnetic field increased cellular cytotoxicity and cellular uptake in association with improved DOX delivery. In addition, the in vivo study of tumor volume showed that tumor growth of the mice group treated with CPUM-DOX-SPION in the presence of an external magnetic field was significantly retarded, with no apparent loss of body weight, compared with the same magnetomicelles in the absence of the magnetic field and with free DOX at the same dose. Moreover, the in vivo MRI experiment indicated the potential of these magnetomicelles as a probe in MRI diagnosis for tumor targeting, and the results showed that magnetically guided delivery of CPUM-SPION magnetomicelles into tumors could significantly improve the targeting efficacy. All the results suggest that the prepared novel magnetomicelles will be promising theranostic systems for effective magnetically guided delivery of chemotherapeutic agents and image-guided personalized medicine.

Design, optimization and characterization of a novel antibacterial chitosan-based hydrogel dressing for promoting blood coagulation and full-thickness wound healing: A biochemical and biophysical study.

The use of hydrogel dressings has become increasingly popular as a scaffold for skin tissue engineering. Herein, we have developed an innovative wound dressing using chitosan, fibrinogen, nisin, and EDTA as an effective antibacterial scaffold for wound treatment. The structural and functional characteristics of the hydrogel, including morphology, mechanical strength, drug encapsulation and release, swelling behaviors, blood coagulation, cytotoxicity, and antibacterial activity, were studied. Spectroscopic studies indicated that the attachment of chitosan to fibrinogen is associated with minimal change in its secondary structure; subsequently, at higher temperatures, it is expected to preserve fibrinogen's conformational stability. Mechanical and blood coagulation analyses indicated that the incorporation of fibrinogen into the hydrogel resulted in accelerated clotting and enhanced mechanical properties. Our cell studies showed biocompatibility and non-toxicity of the hydrogel along with the promotion of cell migration. In addition, the prepared hydrogel indicated an antibacterial behavior against both Gram-positive and Gram-negative bacteria. Interestingly, the in vivo data revealed enhanced tissue regeneration and recovery within 17 days in the studied animals. Taken together, the results obtained from in vitro and histological assessments indicate that this innovatively designed hydrogel shows good potential as a candidate for wound healing.

Improved infectious burn wound healing by applying lyophilized particles containing probiotics and prebiotics.

Lactiplantibacillus plantarum cells were encapsulated in a mixture of cationic and anionic polymers, with the final composition stabilized through freeze-drying. A D-optimal design was used to examine the effects of different polymer concentrations as well as adding prebiotics on the probiotic viability and swelling behavior of the formulations. Scanning electron micrographs revealed stacked particles capable of rapidly absorbing significant amounts of water. These images corresponded to initial swelling percentages of around 2000% for the optimal formulation. The optimized formula had a viability percentage of more than 82%, with the stability studies suggesting that the powders should be stored at refrigerated temperatures. The physical characteristics of the optimized formula were examined to ensure compatibility with its application. According to antimicrobial evaluations, the difference in pathogen inhibition between formulated and fresh probiotics was less than a logarithm. The final formula was tested in vivo and showed improved wound healing indicators. The optimized formula resulted in a higher rate of wound closure and infection clearance. Furthermore, the molecular studies for oxidative stress indicated that the formula could modify wound inflammatory responses. In histological investigations, the probiotic-loaded particles functioned exactly as efficaciously as silver sulfadiazine ointment did.

Redox-responsive waterborne polyurethane nanocarriers for targeted doxorubicin delivery.

Nanocarriers of different origins that respond to stimuli have been synthesized and used in various biomedical applications, such as intracellular drug delivery. To develop highly efficient nanocarriers, novel clickable and cleavable soybean oil-based polyurethane nanomicelles (CPUM), and polyurethane-hyaluronic acid nanomicelles (CPUM-HA) were prepared. The prepared nanocarriers exhibited controlling self-assembly properties, stimuli-responsiveness, good cytocompatibility, and high loading capacity for doxorubicin (DOX). The addition of the reducing agent glutathione (GSH) to the drug release medium resulted in GSH-triggered species size change (aggregation of nanomicelles) and enhanced release of DOX, leading to higher cytotoxicity in tumors. MTT, confocal laser scanning microscopy (CLSM), and flow cytometry results showed that the CPUM-HA-DOX nanocarriers exhibited increased cytotoxicity and cellular uptake compared to the CPUM-DOX nanocarriers. The in vivo and ex vivo results suggested that the CPUM-HA nanomicelles could provide a potential platform for effective targeted delivery of cytotoxic drug molecules to the tumor tissue and breast cancer therapy in the clinic.

Dual drug delivery system based on layered double hydroxides/carboxymethyl cellulose-poly ethylene oxide bionanocomposite electrospun fibrous mats: Fabrication, characterization, in-vitro and in-vivo studies.

The main goal of the present project was to design and develop ibuprofen (IBU) and layered double hydroxides-vancomycin (LDH-VAN) nanohybrid loaded bionanocomposite fibrous mats to increase the wound healing rate. Thus, first, LDH-VAN nanohybrid particles was synthesized by in-situ incorporation of VAN into the Mg-Al-LDH interlayers during the co-precipitation of hydroxides. Then, LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats were fabricated by electrospinning technique. Test samples were examined XRD, SEM, TEM, TGA, and FTIR. In vitro drug release test was performed in the phosphate buffer solution (pH = 7.4) to prove the efficiency of the fabricated bionanocomposite fibrous mats as a sustained-release carrier for both VAN and IBU. All the fabricated bionanocomposite fibrous mats did not displayed any significant cytotoxicity on NIH/3 T3 fibroblast cells. The wound area in the rats treated with LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats was less than other treatment groups. Based on histological analysis, the LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats possess a faster wound healing than other nanofibrous mats. Data obtained from the present project indicated that LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats could accelerate the wound healing process.

Montmorillonite-Famotidine/Chitosan Bio-nanocomposite Hydrogels as a Mucoadhesive/Gastroretentive Drug Delivery System.

The main purpose of the present study was to fabricate mucoadhesive bio-nanocomposite hydrogels to prolong the drug retention time in the stomach. In these bio-nanocomposite hydrogels, chitosan (CH) was used as a bioadhesive matrix, montmorillonite (MMT) was applied to modulate the release rate, and tripolyphosphate (TPP) was the cross-linking agent. The test samples were analyzed via different methods such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). Drug incorporation efficacy and mucoadhesive strength of these nanocomposite hydrogel beads were studied. Swelling and in vitro drug release behaviors of these bio-nanocomposite hydrogels were evaluated in simulated gastric fluid (SGF; pH 1.2). The optimized MMT-famotidine (FMT)/CH bio-nanocomposite hydrogels displayed a controllable and sustainable drug release profile with suitable mucoadhesion and prolonged retention time in the stomach. Thus, the results demonstrated that the fabricated mucoadhesive bio-nanocomposite hydrogels could remarkably increase the therapeutic efficacy and bioavailability of FMT by the oral route.

Development of PVA/Chitosan-g-Poly (N-vinyl imidazole)/TiO2/curcumin nanofibers as high-performance wound dressing.

In this study, electrospun Poly(vinyl alcohol)/Chitosan-g-Poly (N-vinyl imidazole) (PVA/CS-g-PNVIM) wound dressing containing Titanium dioxide/Curcumin (CUR) was prepared as a novel wound healing system with multifunctional properties, including wound closure, drug release, and antibacterial activity. The wound dressing nanofibers system's mechanical, structural, and biological properties were investigated using tensile testing, degradation, X-ray diffraction, Scanning electron microscopy, Fourier transformed infrared spectroscopy, drug release, and in vivo studies. The nanofiber dressing showed excellent mechanical and hydrolytic degradation stability. CS-g-PNVIM-based nanofibers showed excellent antibacterial activity against both Escherichia coli and Staphylococcus aureus in just 1 h with 90 % growth inhibition, with no cytotoxicity to normal fibroblast cells. The animal studies showed that the wound healing and tissue regeneration process by CS-g-PNVIM-based nanofibers were faster than the control group and was completed in 14 days. In conclusion, the CS-g-PNVIM-based nanofibers are potentially promising for biocompatible antibacterial wound dressing applications with proper exudate absorption.

Dual drug delivery system of teicoplanin and phenamil based on pH-sensitive silk fibroin/sodium alginate hydrogel scaffold for treating chronic bone infection.

For effective treatment of infected bone, it is essential to use local drug delivery systems with the ability to deliver both antibiotics and osteoinductive factors. Herein, a pH-sensitive silk fibroin (SF)/sodium alginate (SA) hydrogel scaffolds containing teicoplanin (TEC) and phenamil (PM) loaded SF nanoparticles (PMSFNPS) are introduced for treating chronic osteomyelitis. The TEC and PM showed a sustained- and pH-sensitive release behavior from SF/SA hydrogel. The higher release rate was seen in an alkaline pH in comparison to neutral and acidic pH during 10 days. The eluted TEC maintained its antibacterial activity of >75 % during 35 days and in three different pH values (5.5, 7.4, and 8.5). The cellular study indicated that the scaffolds containing PMSFNPs could promote the cell viability, ALP activity, and matrix mineralization. Moreover, the in vivo effectiveness of hydrogel scaffolds were analyzed with radiography, histological and Immunohistochemistry evaluations. The lower infection and higher regeneration were observed in methicillin-resistant Staphylococcus aureus (MRSA) infected rat bone treated with hydrogel scaffold containing PMSFNPs and TEC compared to other groups. Consequently, this dual-drug delivery system could be a hopeful approach for effective treatment of chronic bone infection.

Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer.

Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.

Impact of oxygen-calcium-generating and bone morphogenetic protein-2 nanoparticles on survival and differentiation of bone marrow-derived mesenchymal stem cells in the 3D bio-printed scaffold.

Although stem cell therapy is a major area of interest in tissue engineering, providing proper oxygen tension, good viability, and cell differentiation remain challenges in tissue-engineered scaffolds. In this study, an osteogenic scaffold was fabricated using the 3D bio-printing technique. The bio-ink contained alginate hydrogel, encapsulated human bone marrow-derived mesenchymal stem cells (hBM-MSCs), calcium peroxide nanoparticles (CPO NPs) as an oxygen generating biomaterial, and bone morphogenic protein-2 nanoparticles (BMP2 NPs) as an osteoinductive growth factor. CPO NPs were synthesized with the hydrolysis-precipitation method, and their concentrations in the bio-ink were optimized. Scaffolds containing CPO 3% (w/w) were preferred, because they generated sufficient oxygen gas for 20 days, increased mechanical strength after 20 days, and had sufficient stability. The CPO NPs effect on the viability of embedded hBM-MSCs under hypoxic conditions was analyzed. Live/Dead staining results represented a 22% improvement in CPO 3% scaffold viability on day 7. Therefore, CPO NPs constituted a promising survival factor. BMP2 NPs were prepared with the double emulsification technique. The incorporation of both BMP2 and CPO NPs resulted in the upregulation of Runt-related transcription factor 2, Collagen type I alpha 1, and the osteocalcin genes compared to internal references in osteogenic media. Overall, the proposed 3D bio-printed osteogenic scaffold in this study has moved scientific research one step forward toward successful stem cell therapy and helped improve host tissue healing by biological activity enhancement, especially for low oxygen pressure tissues.

Designing a new alginate-fibrinogen biomaterial composite hydrogel for wound healing.

Wound healing is a complex process and rapid healing necessitates a proper micro-environment. Therefore, design and fabrication of an efficacious wound dressing is an impressive innovation in the field of wound healing. The fabricated wound dressing in this scenario was designed using a combination of the appropriate coagulating and anti-bacterial materials like fibrinogen (as coagulating agent), nisin (as anti-bacterial agent), ethylenediaminetetraacetic acid (as anti-bacterial agent), and alginate (as wound healing agent). Biophysical characterization showed that the interaction of fibrinogen and alginate was associated with minor changes in the secondary structure of the protein. Conformational studies showed that the protein was structurally stable at 42 °C, is the maximum temperature of the infected wound. The properties of the hydrogel such as swelling, mechanical resistance, nisin release, antibacterial activity, cytotoxicity, gel porosity, and blood coagulation were assessed. The results showed a slow release for the nisin during 48 h. Antibacterial studies showed an inhibitory effect on the growth of Gram-negative and Gram-positive bacteria. The hydrogel was also capable to absorb a considerable amount of water and provide oxygenation as well as incorporation of the drug into its structure due to its sufficient porosity. Scanning electron microscopy showed pore sizes of about 14-198 µm in the hydrogel. Cell viability studies indicated high biocompatibility of the hydrogel. Blood coagulation test also confirmed the effectiveness of the synthesized hydrogel in accelerating the process of blood clot formation. In vivo studies showed higher rates of wound healing, re-epithelialization, and collagen deposition. According to the findings from in vitro as well as in vivo studies, the designed hydrogel can be considered as a novel attractive wound dressing after further prerequisite assessments.

Enhanced BBB and BBTB penetration and improved anti-glioma behavior of Bortezomib through dual-targeting nanostructured lipid carriers.

The effective treatment of glioma through conventional chemotherapy is proved to be a great challenge in clinics. The main reason is due to the existence of two physiological and pathological barriers respectively including the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) that prevent most of the chemotherapeutics from efficient delivery to the brain tumors. To address this challenge, an ideal drug delivery system would efficiently traverse the BBB and BBTB and deliver the therapeutics into the glioma cells with high selectivity. Herein, a targeted delivery system was developed based on nanostructured lipid carriers (NLCs) modified with two proteolytically stable D-peptides, D8 and RI-VAP (Dual NLCs). D8 possesses high affinity towards nicotine acetylcholine receptors (nAChRs), overexpressed on brain capillary endothelial cells (BCECs), and can penetrate through the BBB with high efficiency. RI-VAP is a specific ligand of cell surface GRP78 (csGRP78), a specific angiogenesis and cancer cell-surface marker, capable of circumventing the BBTB with superior glioma-homing property. Dual NLCs could internalize into BCECs, tumor neovascular endothelial cells, and glioma cells with high specificity and could penetrate through in vitro BBB and BBTB models with excellent efficiency compared to non-targeted or mono-targeted NLCs. In vivo whole-animal imaging and ex vivo imaging further confirmed the superior targeting capability of Dual NLCs towards intracranial glioma. When loaded with Bortezomib (BTZ), Dual NLCs attained the highest therapeutic efficiency by means of superior in vitro cytotoxicity and apoptosis and prolonged survival rate and efficient anti-glioma behavior in intracranial glioma bearing mice. Collectively, the designed targeting platform in this study could overcome multiple barriers and effectively deliver BTZ to glioma cells, which represent its potential for advanced brain cancer treatment with promising therapeutic outcomes.

pH-Responsive, Adorned Nanoniosomes for Codelivery of Cisplatin and Epirubicin: Synergistic Treatment of Breast Cancer.

Combination chemotherapy has become a treatment modality for breast cancer. However, serious side effects and high cytotoxicity associated with this combination therapy make it a high-risk method for breast cancer treatment. This study evaluated the anticancer effect of decorated niosomal nanocarriers loaded with cisplatin (CIS) and epirubicin (EPI) in vitro (on SKBR3 and 4T1 breast cancer cells) and in vivo on BALB/c mice. For this purpose, polyethylene glycol (PEG) and folic acid (FA) were employed to prepare a functionalized niosomal system to improve endocytosis. FA-PEGylated niosomes exhibited desired encapsulation efficiencies of ∼91.2 and 71.9% for CIS and EPI, respectively. Moreover, cellular assays disclosed that a CIS and EPI-loaded niosome (NCE) and FA-PEGylated niosomal CIS and EPI (FPNCE) enhanced the apoptosis rate and cell migration in SKBR3 and 4T1 cells compared to CIS, EPI, and their combination (CIS+EPI). For FPNCE and NCE groups, the expression levels of Bax, Caspase3, Caspase9, and Mfn1 genes increased, whereas the expression of Bcl2, Drp1, MMP-2, and MMP-9 genes was downregulated. Histopathology results showed a reduction in the mitosis index, invasion, and pleomorphism in BALB/c inbred mice with NCE and FPNCE treatment. In this paper, for the first time, we report a niosomal nanocarrier functionalized with PEG and FA for codelivery of CIS and EPI to treat breast cancer. The results demonstrated that the codelivery of CIS and EPI through FA-PEGylated niosomes holds great potential for breast cancer treatment.

Fabrication of Silk Scaffold Containing Simvastatin-Loaded Silk Fibroin Nanoparticles for Regenerating Bone Defects

Background: In the present study, a tissue engineered silk fibroin (SF) scaffold containing simvastatin-loaded silk fibroin nanoparticles (SFNPs) were used to stimulate the regeneration of the defected bone. Methods: At first, the porous SF scaffold was prepared using freeze-drying. Then simvastatin-loaded SFNPs were made by dissolvation method and embedded in the SF scaffold. Afterwards, the scaffold and the NPs were characterized in terms of physicochemical properties and the ability to release the simvastatin small molecule. Results: The results exhibited that the SF scaffold had a porous structure suitable for releasing the small molecule and inducing the proliferation and attachment of osteoblast cells. SFNPs containing simvastatin had spherical morphology and were 174 ± 4 nm in size with -24.5 zeta potential. Simvastatin was also successfully encapsulated within the SFNPs with 68% encapsulation efficiency. Moreover, the small molecule revealed a sustained release profile from the NPs during 35 days. The results obtained from the in vitro cell-based studies indicated that simvastatin-loaded SFNPs embedded in the scaffold had acceptable capacity to promote the proliferation and alkaline phosphatase production of osteoblast cells while inducing osteogenic matrix precipitation. Conclusion: The SF scaffold containing simvastatin-loaded SFNPs could have a good potential to be used as a bone tissue-engineered construct.