Investigation and multiscale modeling of PVA/SA coated poly lactic acid scaffold containing curcumin loaded layered double hydroxide nanohybrids.

Applying hydrophilic coatings on polymeric nanofibers combined with layered double hydroxide (LDH) not only enhances the efficiency of drug delivery systems but also increases cell adhesion. This work aimed to prepare poly(vinyl alcohol)/sodium alginate (PVA/SA) (2/1)-coated poly(lactic acid) (PLA) nanofibers containing curcumin-loaded layered double hydroxide (LDH) and to investigate their drug release and mechanical properties and their biocompatibility. The optimum PLA nanofibrous sample was considered to be that based on 3 wt% of curcumin-loaded LDH (PLA-3%LDH) with a drug encapsulation efficiency of ∼18% in which a minimum average nanofiber diameter of ∼476 nm along with a high tensile strength of 3.00 MPa were obtained. In the next step, a PVA/SA (2/1) layer was coated on the PLA-3%LDH; as a result, the hydrophilicity of the sample was improved and the elongation at break was decreased remarkably. In this regard the cell viability reached 80% for the coated PLA. Moreover, the formation of a layer of (PVA/SA) on the PLA nanofibers lowered the burst release and resulted in a more sustained drug release, which is a vital feature in dermal applications. A multiscale modeling method was applied for simulation of the mechanical properties of the composite scaffold and the results showed that this method can predict the data with 83% accuracy. The results of this study indicate that the formation of a layer of PVA/SA (2/1) has a significant effect on hydrophilicity and consequently improves cell adhesion and proliferation.

Synthesis, Solvatochromism and Fluorescence Quenching Studies of Naphthalene Diimide Dye by Nano graphene oxide.

A naphthalene diimide dye with two side amine arm was prepared. Uv-Vis and fluorescence spectroscopic techniques are used for their photophysical and solvatochromic characteristics in different solvents. The Lippert-Mataga plot for naphthalene diimide demonstrated a negative linear dependence by increasing polarity. Results showed naphthalene diimide is more polar in the ground than in the excited state. A quenching study was conducted for interacting the naphthalene diimide as a fluorophore and graphene oxide as a quencher. Fluorescence quenching-based platforms in nanoscale have been used in sensing systems. Raman, FTIR, Uv-Vis and fluorescence spectroscopic techniques were used to study the quenching mechanism. The results indicated that graphene plays an effective quencher against the naphthalene diimide, with a quenching efficiency 91%. The Stern-Volmer analysis results show a mix of static and dynamic quenching mechanisms. The binding constant of the quencher-fluorophore and the number of binding sites have been reported. Thermodynamic parameters of their interaction were evaluated. The negative values of the Gibbs free energy confirm that the complexation process is spontaneous. Meanwhile, the positive entropy value confirms that the favorable pathway process.

Microfluidics combined with ionic gelation method for production of nanoparticles based on thiol-functionalized chitosan to adsorb Hg (II) from aqueous solutions.

This work aimed at producing nanoparticles (NPs) based on thiol-functionalized chitosan (CS) using capillary microfluidic (MF) device combined with ionic gelation method to adsorb mercury ion [Hg (II)] from aqueous solutions. In this line, CS was functionalized with epichlorohydrin/cysteaminium chloride (2.73 M ratio) followed by fabricating NPs via MF and bulk mixing (BM) methods. To characterize the morphology, zeta potential, functionality, structure, and magnetic property of the samples, a series of tests such as SEM, TEM, DLS, FTIR, XRD, and VSM were carried out, respectively. The obtained results showed that MF technique was able to produce NPs with a diameter as small as 18 ±â€¯3 nm, and a uniform shape compared to BM method. Thiol groups (-SH) functionalization on CS surface was confirmed by appearing a characteristic peak at 2579 cm-1. Also, the XRD patterns indicated the appropriate synthesis of Fe3O4 (magnetite), and no change in the structure of CS NPs in the presence of magnetite. Moreover, adding the magnetite to thiol-functionalized CS NPs led to suitable saturation magnetization about 26 emu/g to facilitate their separation using a magnetic field. To evaluate the performance of the nanoadsorbent, it has been exposed to Hg (II) in an aqueous solution which in turn the parameters optimization for the adsorption was done via Box-Behnken design (BBD) method, exhibiting the effect of adsorbent dose and the initial concentration of Hg (II) was much more significant than that of pH. Different concentrations of total dissolved solids up to 1000 mg/L had no adverse impact on the adsorption process confirmed by EDAX spectra. The least value of RMSE (5.023) and χ2 (0.3) were observed for Redlich-Peterson, Radke-Prausnitz, and UT isotherms. Maximum adsorption capacities calculated using Langmuir and UT models were 1192 mg/g and 1126 mg/g, respectively. Thermodynamic studies demonstrated that the nature of the adsorption process was spontaneous and endothermic. Recovery of nanoadsorbent was successfully carried out using HCl 0.5 mol/L. The adsorption studies revealed that the prepared nanoadsorbent is promising candidate used in mercury removal from a real wastewater potentially.

Potential use of a bone tissue engineering scaffold based on electrospun poly (ɛ-caprolactone) - Poly (vinyl alcohol) hybrid nanofibers containing modified cockle shell nanopowder.

Today, the construction of scaffolds promoting the differentiation of stem cells is an intelligent innovation that accelerates the differentiation toward the target tissue. The use of calcium and phosphate compounds is capable of elevating the precision and efficiency of the osteogenic differentiation of stem cells. In this research, osteoconductive electrospun poly (ɛ-caprolactone) (PCL) - poly (vinyl alcohol) (PVA) hybrid nanofibrous scaffolds containing modified cockle shell (CS) nanopowder were prepared and investigated. In this regard, the modified CS nanopowder was prepared by grinding and modifying with phosphoric acid, and it was then added to PVA nanofibers at different weight percentages. Based on the SEM images, the optimum content of the modified CS nanopowder was set at 7 wt %, since reaching the threshold of agglomeration restricted this incorporation. In the second step, the PVA-CS7 nanofibrous sample was hybridized with different PCL ratios. Concerning the hydrophilicity and mechanical strength, the sample named PCL50-PVA50-CS7 was ultimately selected as the optimized and suitable candidate scaffold for bone tissue application. The accelerated hydrolytic degradation of the sample was also studied by FTIR and SEM analyses, and the results confirmed that the mineral deposits of CS are available approximately 7 days for mesenchymal stem cells. Moreover, Alizarin red staining illustrated that the presence of CS in the PCL50-PVA50-CS7 hybrid nanofibrous scaffold may potentially lead to an increase in calcium deposits with high precipitates, authenticating the differentiation of stem cells towards osteogenic cells.

Fabrication of fiber-particle structures by electrospinning/electrospray combination as an intrinsic antioxidant and oxygen-releasing wound dressing.

In this study, we employed a combination of electrospinning and electrospray techniques to fabricate wound dressings with a particle-fiber structure, providing dual characteristics of oxygen-releasing and intrinsic antioxidant properties, simultaneously. The electrospun part of the dressing was prepared from a blend of polycaprolactone/gallic acid-grafted-gelatin (GA-g-GE), enabling intrinsic ROS scavenging. To the best of our knowledge, this is the first time that PCL/GA-g-GE was fabricated by electrospinning. Furthermore, polyvinyl pyrrolidone (PVP) microparticles, containing calcium peroxide nanoparticles (CNPs), were considered as the oxygen production agent through the electrospray part. The CNP content was 1% and 3% w/w of PVP while biopolymer:PCL was 10% w/w. The fabricated structures were characterized in terms of fiber/particle morphology, elemental analysis, oxygen release behavior, ROS inhibition capacity, and water contact angle assessments. The covalent bonding of gallic acid to gelatin was confirmed by 1H-NMR, UV spectroscopy, and FTIR. According to the SEM results, the morphology of the prepared PCL/biopolymer fibers was bead-free and with a uniform average diameter. The analysis of released oxygen showed that by increasing the weight percentage of CNPs from 1 to 3 wt%, the amount of released oxygen increased from 120 mmHg to 195 mmHg in 24 h, which remained almost constant until 72 h. The obtained DPPH assay results revealed that the introduction of GA-g-GE into the fibrous structure could significantly improve the antioxidant properties of wound dressing compared to the control group without CNPs and modified gelatine. In vitro, the fabricated wound dressings were evaluated in terms of biocompatibility and the potential of the dressing to protect human dermal fibroblasts under oxidative stress and hypoxia conditions by an MTT assay. The presence of GA-g-GE led to remarkable protection of the cells against oxidative stress and hypoxia conditions. In vivo studies revealed that the incorporation of intrinsic ROS inhibition and oxygen-releasing properties could significantly accelerate the wound closure rate during the experimental period (7, 14, and 21 days). Additionally, histopathological investigations in terms of H&E and Masson's trichrome staining showed that the incorporation of the two mentioned capabilities remarkably facilitated the wound-healing process.

Neoplastic cell response to tiopronin-coated gold nanoparticles.

The present study characterized the in vitro biological response of a comprehensive set of cancer cell lines to gold nanoparticles (2.7 nm) coated with tiopronin (AuNPs-TP). Our findings suggest that upon entering cells, the AuNPs-TP are sequestered in vacuoles such as endosomes and lysosomes, and mostly localize in perinuclear areas. Peak cell accumulation was achieved at 8 hours after incubation. L929 and H520 cells showed more than 75% surviving fraction when treated with 0.5 mg/mL of AuNPs-TP for 24 hours, whereas the surviving fractions were 60% in MCF-7 and 20% in HeLa cells. Reactive oxygen species (ROS) production by the AuNPs-TP was dependent on cell line and exposure time. Antioxidants inhibited ROS generation to various extents, with glutathione and tiopronin being most effective. Overall, exposure time, concentration of the AuNPs-TP, and cell line influenced neoplastic cell response. Furthermore, the mechanism of cytotoxicity of the AuNPs-TP was found to be ROS generation. FROM THE CLINICAL EDITOR: This study describes the basic intracellular characteristics of Tiopronin-Au nanoparticles from the standpoint of their anti-cancer activity in different cancer cell cultures.

Improvement of Intracellular Interactions through Liquid Crystalline Elastomer Scaffolds by the Alteration of Topology.

Preparation of inherently bioactive scaffolds has become a challenging issue owing to their complicated synthesis and nonrobust modified cell-actuating property. Liquid crystalline elastomers (LCEs), due to their combined specialties of liquid crystals and elastomers as well as their ability to respond to various kinds of stimuli, have reversibly led to the design of a new class of stimuli-responsive tissue-engineered scaffolds. In this line, in the first stage of this research work, synthesis and evaluation of acrylate-based LCE films (LCEfilm) encompassing mesogenic monomers are carried out. In the second step, the design of an affordable electrospinning technique for preparing LCE nanofibers (LCEfiber) as a problematic topic, thanks to the low molecular weight of the mesogenic chains of LCEs, is investigated. For this purpose, two approaches are considered, including (1) photo-cross-linking of electrospun LCEfiber and (2) blending LCE with poly(ε-caprolactone) (PCL) to produce morphologically stable nanofibers (PCL-LCEfiber). In the following, thermal, mechanical, and morphological evaluations show the optimized crosslinker (mol)/aliphatic spacer (mol) molar ratio of 50:50 for LCEfilm samples. On the other hand, for LCEfiber samples, the appropriate amounts of excessive mesogenic monomer and PCL/LCE (v/v) to fabricate the uniform nanofibers are determined to be 20% and 1:2, respectively. Eventually, PC12 cell compatibility and the impact of the liquid crystalline phase on the PC12 cell dynamic behavior of the samples are examined. The obtained results reveal that PC12 cells cultured on electrospun PCL-LCEfiber nanofibers with an average diameter of ∼659 nm per sample are alive and the scaffold has susceptibility for cell proliferation and actuation because of the rapid increase in cell density and number of singularity points formed in time-lapse cell imaging. Moreover, the PCL-LCEfiber nanofibrous scaffold exhibits a high performance for cell differentiation according to detailed biological evaluations such as gene expression level measurements. The time-lapse evaluation of PC12 cell flow fields confirms the significant influence of the reprogrammable liquid crystalline phase in the PCL-LCEfiber nanofibrous scaffold on topographical cue induction compared to the biodegradable PCL nanofibers.

Lawsonia inermis-loaded poly (L-lactide-co-D, L-lactide) nanofibers for healing acceleration of burn wounds.

This study aimed to develop a new bioactive wound dressing based on electrospun poly (L-lactide-co-D, L-lactide) (PLDLLA) nanofibers containing Lawsonia inermis (LI) for burn wounds. The SEM results showed that loading LI increased the average diameter of PLDLLA nanofibers to 528 nm with smooth and beadless morphology. The analysis of LI release from PLDLLA nanofibers and film samples was measured by UV-vis spectrophotometry, and the obtained results revealed that LI molecules could diffuse from the nanofibrous sample with higher rate than film during 48 h. In this regard, the PLDLLA nanofibrous sample as a drug carrier has advantages compared to the film. Moreover, the antibacterial results confirmed the positive influence of LI related to the bacteria which in turn the growth inhibition zones were increased from 6 to 22 mm for P. aeruginosa, and from 3 to 16 mm for S. aureus while the LI concentration was set at 1.4% (w/v). Finally, animal model studies demonstrated that PLDLLA-LI nanofibers accelerated burn wound closure remarkably; thereby decreasing the wound area approximately 90% during the treatment period of 19 days. The histological observations dedicated that the appearance of the epithelial layer was increased dramatically alongside the thickness of around 40% for the wound treated with PLDLLA-LI nanofibrous sample rather than that without LI. Besides the epithelialization, it has been found that the wound covered by PLDLLA-LI wound dressing has condensed collagen fibers with no necrosis.

Kiwi extract-incorporated poly(ɛ-caprolactone)/cellulose acetate blend nanofibers for healing acceleration of burn wounds.

Kiwi extract (KE) including different components such as quercetin, vitamins C and E, and actinides has been known as a debridement agent for burn wounds. In this study, electrospun poly(ɛ-caprolactone)/cellulose acetate blend nanofibers incorporating KE (PCL/CA/KE) were prepared and their performance was evaluated for healing acceleration of burn wounds. The physicochemical characterization of PCL/CA/KE nanofibers showed an average diameter of ∼420 nm, porosity of 70%, water contact angle of 61°, and water uptake of ∼220%. Moreover, the continuous release trend of KE from PCL/CA blend nanofibers happened during 24 h and the release mechanism was governed by the Fickian diffusion. Besides the cytocompatibility of PCL/CA/KE nanofibers, their in vivo experiments revealed that the bioactive wound dressing based on the sample has higher wound closure compared to KE after 21 days. Histopathology of wounds dressed by PCL/CA/KE nanofibers indicated epidermal formation along with a fully extended layer. Eventually, the obtained results confirmed that the PCL/CA/KE nanofibrous sample was a promising wound dressing for burn wound healing.

Green synthesis of chitosan/polyacrylic acid/graphitic carbon nitride nanocarrier as a potential pH-sensitive system for curcumin delivery to MCF-7 breast cancer cells.

A novel pH-sensitive nanocarrier containing chitosan (CS), polyacrylic acid (PAA), and graphitic carbon nitride (g-C3N4) was designed via water/oil/water (W/O/W) emulsification to administer curcumin (CUR) drug. g-C3N4 nanosheets with a high surface area and porous structure were produced via simple one-step pyrolysis process using thiourea as precursor, and incorporated into CS/PAA hydrogel. X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to assess the crystalline structure of the nanocarrier and the interactions between its components, respectively. Scanning electron microscopy (SEM) images revealed a spherical structure and confirmed the g-C3N4 impregnation into the CS/PAA matrix. Zeta potential and dynamic light scattering (DLS) provided information about the surface charge and average size distribution. High CUR loading and entrapment efficiencies were obtained, which were further improved upon addition of g-C3N4. The release kinetics of drug-loaded CS/PAA/g-C3N4 nanocomposites were investigated at pH = 5.4 and pH = 7.4, and the results showed an excellent controlled pH-sensitive release profile. Cell apoptosis and in vitro cytotoxicity were investigated using flow cytometry and MTT analyses. CS/PAA/g-C3N4/CUR resulted in the highest rate of apoptosis in MCF-7 breast cancer cells, demonstrating the excellent nanocomposite efficacy in eliminating cancerous cells. CS/PAA hydrogel coated with g-C3N4 shows great potential for pH-sensitive controlled drug release.

Combination drug delivery strategy for the treatment of multidrug resistant ovarian cancer.

The onset of multidrug resistance (MDR) in ovarian cancer is one of the main causes of treatment failure and low survival rates. Inadequate drug exposure and treatment-free periods due to intermittent chemotherapy select for cancer cells overexpressing drug efflux transporters, resulting in resistant disease. The present study examines the sustained administration of the chemotherapeutic agent docetaxel (DTX) alone and in combination with cepharanthine (CEP), a potent drug efflux transporter inhibitor. DTX and CEP were delivered via the intraperitoneal route in a sustained manner using an injectable polymer-lipid formulation. In vitro, the combination strategy resulted in significantly (p < 0.05) more apoptosis, greater intracellular accumulation of DTX, and lower DTX efflux in ovarian cancer cells showing the MDR phenotype. In vivo, sustained treatment with DTX and CEP showed significantly greater (p < 0.05) tumor inhibition (91 ± 4%) in a murine model of multidrug resistant ovarian cancer compared to sustained DTX treatment (76 ± 6%) and was more than twice as efficacious as intermittent DTX treatment. Overall findings from these studies highlight the impact of sustained delivery of monotherapy and combination therapy in the management of refractory ovarian cancer displaying the MDR phenotype.

Docetaxel distribution following intraperitoneal administration in mice.

PURPOSE: Intraperitoneal (IP) chemotherapy with high molecular weight lipophilic antineoplastic agents such as the taxanes has shown promise in clinical trial evaluation for treatment of localized peritoneal cancers. We have previously developed an IP injectable hydrogel formulation (PoLigel) for sustained peritoneal delivery of docetaxel (DTX), and observed significant efficacy in murine models of ovarian cancer when compared to Taxotere®, the FDA approved formulation of DTX. In order to understand the relationship between drug distribution and efficacy, the current study compares the tissue distribution and pharmacokinetics of DTX administered IP in the PoLigel or Taxotere® formulations. METHODS: The PoLigel was prepared by blending a water-soluble chitosan derivative, egg phosphatidylcholine and lauric aldehyde with DTX (drug to material ratio 1:8 w/w). DTX concentrations in plasma, heart, liver, spleen, stomach, intestine, kidney and peritoneal muscle were measured over a five day period following IP administration of the PoLigel and Taxotere® formulations in CD-1 female mice. RESULTS: Three days after Taxotere® administration, no detectable levels of DTX were seen in plasma, while sustained DTX plasma levels of 0.06 ug/ml ± 0.01 per day were observed with PoLigel. At five days post Taxotere® administration, only intestine, stomach and peritoneal muscle showed detectable DTX concentrations whereas all tissues and plasma showed sustained DTX levels in mice that received PoLigel. DTX concentrations that resulted from PoLigel administration were significantly higher in the peritoneal cavity and 200 fold higher than concentrations found in plasma. CONCLUSIONS: Overall, the PoLigel formulation increases tissue and plasma drug retention and provides sustained DTX levels compared to the clinically used Taxotere® formulation. The sustained DTX levels seen in the peritoneal cavity following IP administration of the PoLigel may be responsible for the improvement in efficacy that has been observed in our previous studies.

Microfluidic-based synthesized carboxymethyl chitosan nanoparticles containing metformin for diabetes therapy: In vitro and in vivo assessments.

This work was aimed to synthesize novel crosslinked carboxymethyl chitosan nanoparticles (CMCS NPs) containing metformin hydrochloride (MET) using microfluidics (MF) and evaluate their performance for diabetes therapy. The field emission-scanning electron microscopy (FE-SEM) images and dynamic light scattering (DLS) results showed that the NPs average size was 77 ± 19 nm with a narrow size distribution. They exhibited a high encapsulation efficiency (∼90 %) and the controlled drug release while crosslinking using CaCl2. Eventually, the in vivo assessments dedicated an increased body weight up to 7.94 % and a decreased blood glucose level amount of 43.58 % for MF MET-loaded CMCS NPs with respect to the free drug in diabetic rats. Also, the results of histopathological studies revealed the size of the pancreatic islets to be 2.32 µm2 and ß cells intensity to be 64 cells per islet for the diabetic rats after treating with the MF-based sample. These data were close to those obtained for the healthy rats.

Osteogenesis enhancement using poly (l-lactide-co-d, l-lactide)/poly (vinyl alcohol) nanofibrous scaffolds reinforced by phospho-calcified cellulose nanowhiskers.

Electrospun poly (l-lactide-co-d, l-lactide) (PLDLLA)/poly (vinyl alcohol) (PVA) nanofibers were reinforced by various contents (0-1 wt%) of phospho-calcified cellulose nanowhiskers (PCCNWs) as scaffolds in bone applications. The hydrophilicity and rate of hydrolytic degradation of PLDLLA were improved by introducing 10 wt% of PVA. PCCNWs with inherent hydrophilic properties, high aspect ratio, and large elastic modulus enhanced the hydrophilicity, accelerated the rate of degradation, and improved the mechanical properties of the nanofibrous samples. Moreover, calcium phosphate and phosphate functional groups on the surface of PCCNWs possessing act as stimulating agents for cellular activities such as proliferation and differentiation. Besides the physico-chemical properties investigation of PLDLLA/PVA-PCCNWs nanofibrous samples, their cytotoxicity was also studied and they did not show any adverse side effect. Incorporation of PCCNWs (1 wt%) into the PLDLLA/PVA nanofibrous samples showed more enzymatic activities and deposited calcium. The micrograph images of the morphology of human mesenchymal stem cells (hMSCs) cultured on the nanofibrous sample containing 1 wt% of PCCNWs after 14 days of cell differentiation revealed their high potential for bone tissue engineering.

Ovarian Cell Encapsulation in an Enzymatically Crosslinked Silk-Based Hydrogel with Tunable Mechanical Properties.

An artificial ovary is a promising approach for preserving fertility in prepubertal girls and women who cannot undergo current cryopreservation strategies. However, this approach is in its infancy, due to the possible challenges of creating a suitable 3D matrix for encapsulating ovarian follicles and stromal cells. To maintain the ovarian stromal cell viability and proliferation, as a first step towards developing an artificial ovary, in this study, a double network hydrogel with a high water swelling capacity (swelling index 15-19) was developed, based on phenol conjugated chitosan (Cs-Ph) and silk fibroin (SF) through an enzymatic crosslinking method using horseradish peroxidase. The addition of SF (1%) to Cs (1%) decreased the storage modulus (G') from 3500 Pa (Cs1) to 1600 Pa (Cs-SF1), and the hydrogels with a rapid gelation kinetic produced a spatially homogeneous distribution of ovarian cells that demonstrated 167% proliferation after 7 days. This new Cs-SF hydrogel benefits from the toughness and flexibility of SF, and phenolic chemistry could provide the potential microstructure for encapsulating human ovarian stromal cells.

Conductive conduit based on electrospun poly (l-lactide-co-D, l-lactide) nanofibers containing 4-aminopyridine-loaded molecularly imprinted poly (methacrylic acid) nanoparticles used for peripheral nerve regeneration.

Using biocompatible polymer nanofibrous conduits with a controlled drug delivery have attracted much attention for peripheral nerve regeneration. This work was aimed at preparing electrospun poly (l-lactide-co-D, l-lactide) (PLDLLA) containing multi-walled carbon nanotubes (MWCNTs) and 4-aminopyridine (4-AP)-loaded molecularly imprinted nanoparticles (MIP4-AP) as well as evaluating their performance in in vitro and in vivo assessments. After synthesis of MIP4-AP based on poly (methacrylic acid) with imprinting factor of 1.78, it was incorporated into the PLDLLA/MWCNTs nanofibers to optimize. By adjusting the process variables, the average diameter and electrical conductivity of the nanofibrous sample were 92 nm and 2870 × 10-7 S cm-1, respectively. Afterward, 4-AP release of the optimum sample showed the presence of MIP4-AP leading to initial burst release decrease and plateau level postpone up to 96 h. Moreover, the culture results of PC12 as neuroblastoma cell line on optimal PLDLLA/MWCNTs/MIP4-AP nanofibrous sample revealed the highest cell proliferation without cytotoxicity compared to neat nanofibers. Eventually, the animal model experiment exhibited that the conductive conduit based on the optimum sample was able to repair the rat's sciatic nerve after four weeks in accordance with sciatic function index and histological studies.

A Novel Approach for Development of Intraocular Biodegradable Ranibizumab Implant: A Solution for Stability of Protein Activity.

Purpose: Ranibizumab is a monoclonal antibody fragment, targeting all isoforms of vascular endothelial growth factor A (VEGF-A), a protein involved in angiogenesis. It is used to treat age-related macular degeneration (AMD), retinal vein occlusion (RVO), and diabetic macular edema (DME), which are associated with blindness worldwide. However, proper treatment can decrease the loss of vision in about 90% of patients. Because of poor drug uptake in topical therapy and several adverse side effects of systemic irregularities and intravitreal injections, sustained-release drug delivery systems are more suitable for treatment. However, there are many challenges in the development of these systems due to the loss of protein activities. Methods: After drug complexation by the ion pairing method and preparation of a polymeric implant, containing the drug, the characteristics of the complexes were examined by Fourier-transform infrared spectroscopy and circular dichroism spectroscopy. The stability of antibody activity and biocompatibility of the released drug from the implant were assessed by bioassays and MTT assay, respectively. Finally, the release kinetics were investigated. Results: The bioassays showed the higher activity of the drug complex, compared to the free form, besides good biocompatibility in vitro. Also, the release data confirmed sustained and controlled release characteristics for the prepared implant. Conclusion: In this study, for the first time, we proposed a method for developing a sustained-release intraocular implant, consisting of ranibizumab by the heating method. This method allows for the industrial production of ranibizumab by extrusion and eliminates the complications related to reservoir systems.

Enhanced osteogenesis using poly (l-lactide-co-d, l-lactide)/poly (acrylic acid) nanofibrous scaffolds in presence of dexamethasone-loaded molecularly imprinted polymer nanoparticles.

The aim of this work is to prepare nanofibrous scaffolds based on poly (l-lactide-d, l-lactide)/poly (acrylic acid) [PLDLLA/PAAc] blends in the presence of Dexamethasone [Dexa]-loaded poly (2-hydroxyethyl methacrylate) [HEMA] as molecular imprinted polymer [MIP] nanoparticles [NPs] for enhancing osteogenesis. By adding 10 wt% of PAAc to the PLDLLA and employing response surface methodology, the average diameter of the electrospun nanofibers is approximately 237 nm. To increase the osteogenesis performance of the optimized nanofibrous scaffolds, the MIP nanoparticles are synthesized using HEMA monomer and Dexa template with a molar ratio of 10 to 1. Accordingly, these crosslinked drug nanocarriers exhibit an average diameter of around 122 nm and imprinting factor of approximately 1.8, enabling to adsorb Dexa molecules around 57%. Afterward, the Dexa-loaded MIP NPs have capability of a controlled drug release with ultimate value of 60% during 72 h. The simultaneous use of PLDLLA/PAAc-10 nanofibrous scaffold and Dexa-loaded MIP NPs within the cultivation media of fibroblast and mesenchymal stem cells is carried out by thiazolyl blue assay and acridine/ethidium bromide staining as well as alkaline phosphate/calcium content test, and alizarin red staining. The results reveal the remarkable efficiency of the blend nanofibers besides the MIP containing Dexa, thereby using for bone tissue engineering applications, potentially.

Microfluidic-Assisted Preparation of 5-Fluorouracil-Loaded PLGA Nanoparticles as a Potential System for Colorectal Cancer Therapy.

This work aims at fabricating 5-fluorouracil (5-FU)-loaded poly (lactic-co-glycolic) acid nanoparticles (PLGA NPs) using a microfluidic (MF) technique, with potential for use in colorectal cancer therapy. In order to achieve 5-FU-loaded NPs with an average diameter of approximately 119 nm, the parameters of MF process with fork-shaped patterns were adjusted as follows: the ratio of polymer to drug solutions flow rates was equal to 10 and the solution concentrations of PLGA as carrier, 5-FU as anti-cancer drug and poly (vinyl alcohol) (PVA) as surfactant were 0.2 (% w/v), 0.01 (% w/v) and 0.15 (% w/v), respectively. In this way, a drug encapsulation efficiency of approximately 95% into the PLGA NPs was obtained, due to the formation of a hydrodynamic flow focusing phenomenon through the MF chip. A performance evaluation of the NP samples in terms of the drug release, cytotoxicity and cell death was carried out. Finally, by analyzing the results after induction of cell death and 4', 6-diamidino-2-phenylin-dole (DAPI) staining, MF-fabricated NPs containing 5-FU [0.2 (% w/v) of PLGA] revealed the dead cell amounts of 10 and 1.5-fold higher than the control sample for Caco2 and SW-480, respectively.

Antibacterial nanofibers based on poly(l-lactide-co-d, l-lactide) and poly(vinyl alcohol) used in wound dressings potentially: a comparison between hybrid and blend properties.

Morphology, hydrophilicity, degradation, mechanical properties, drug release, bacterial resistance, and cell viability are indispensable parameters for a bioactive wound dressing. In this work, the aforementioned terms between hybrid and blend nanofibrous samples based on poly (L-lactide-co-D, L-lactide) (PLDLLA) and poly (vinyl alcohol) (PVA) containing triclosan (Tri) as an antibacterial drug were investigated. The FE-SEM images showed that the presence of Tri in the hybrid and blend samples led to bimodal, and unimodal diameter size distributions. The FTIR spectra revealed that the addition of PVA caused to shift the carbonyl bond of PLDLLA in the blend sample, and DSC thermograms exhibited the immiscibility of PVA and PLDLLA polymers in the blend. Moreover, the hybrid sample showed higher hydrophilicity with water contact angle (WCA) of 53[Formula: see text] than the blend ones with WCA of 73[Formula: see text] which proved by water up-take test. In the following, the antibacterial evaluation showed better results for hybrid-Tri with the maximum growth inhibitory zones of 35 mm and 48 mm for E. coli and S. aureus, respectively. On the other hand, the hybrid nanofibrous sample showed remarkable mechanical properties (tensile stress ∼19 MPa, and Young's modulus ∼532 MPa). Finally, the SNL 76/7 fibroblast cell line culture confirmed that the hybrid-Tri nanofibrous sample had better proliferation performance than the blend-Tri sample because of the minimal cytotoxicity and maximal cell viability by MTT and acridine orange/ethidium bromide staining.