Synthesis and evaluation of modified lens using plasma treatment containing timolol-maleate loaded lauric acid-decorated chitosan-alginate nanoparticles for glaucoma.

Reducing intraocular pressure (IOP) with eye drops is one of the most common ways to control glaucoma. Low bioavailability and high frequency of administration in eye drops are major challenges in ocular pharmacotherapy. Contact lenses have attracted the attention of scientists in recent decades as an alternative method. In this study, with the aim of long-term drug delivery and better patient compatibility, contact lenses with surface modification and nanoparticles were used. In this study, timolol-maleate was loaded into polymeric nanoparticles made of chitosan conjugate with lauric acid and sodium alginate. Then silicon matrix was mixed with a curing agent (10:1), and the suspension of nanoparticles was added to the precursor and cured. Finally, for surface modification, the lenses were irradiated with oxygen plasma at different exposure times (30, 60, and 150 s) and soaked in different BSA concentrations (1, 3, and 5% w/v). The results showed nanoparticles with a size of 50 nm and a spherical shape were synthesized. The best surface modification of the lenses was for 5 (% w/v) albumin concentration and 150 s exposure time, which had the highest increase in hydrophilicity. Drug release from nanoparticles continued for 3 days and this amount increased to 6 days after dispersion in the modified lens matrix. The drug model and kinetic study show the Higuchi model completely supported the release profile. This study represents the novel drug delivery system to control intra-ocular pressure as a candidate platform for glaucoma treatment. Improved compatibility and drug release from the designed contact lenses would prepare new insight into the mentioned disease treatment.

The effect of nanoparticles on pulmonary fibrosis: a systematic review and Meta-analysis of preclinical studies.

Air pollution is a big ecumenical problem associated with public health around the world. The rapid development of nanotechnology worldwide resulted in a significant increase in human exposure with unknown particles, and ultimately leading to an increase in acute and chronic diseases. The effect of nanoparticles on pulmonary fibrosis has been reported in vivo and in vitro studies; however, the results are inconsistent. The present systematic review and meta-analysis of animal preclinical studies was conducted to assess the effect of nanoparticles on pulmonary fibrosis. A systematic search of online databases and gray literature as well as reference lists of retrieved studies was performed up to February 2019 to identify preclinical animal studies. Studies were assessed for methodological quality using the SYstematic Review Center for Laboratory animal Experimentation bias risk tool (SYRCLE's ROB tool). Pooled standardized mean difference (SMD) estimate with corresponding 95% CI was calculated using inverse-variance weights method while random effects meta-analysis was used, taking into account conceptual heterogeneity. To assess the robustness of pooled estimates as well as heterogeneity across studies, sensitivity analysis and Cochran Q statistic (with I2 statistic) was carried out using Stata 11.0. Of 6494 retrieved studies, 85 were reviewed in depth for eligibility. 16 studies met the criteria for inclusion in this systematic review. The meta-analysis was conducted on 10 studies which had reported the mean of TGF-ß in 7 days after exposure by nanoparticles jointly (exposure compared to no exposure). Findings showed that exposure to nanoparticles significantly induced pulmonary fibrosis (SMD: 4.12, 95% CI: 2.57-5.67). A statistical heterogeneity was found [P < 0.001 (Q statistics), I2 = 83.0%] across studies. Nanoparticles were the most influencing in inducing pulmonary fibrosis in animal models. Sensitivity analysis demonstrated consistency of the results, indicating that the meta-analysis model was robust. Publication bias (using visual inspection and statistical tests) was unlikely in the association between nanoparticles and pulmonary fibrosis. We found that the nanoparticles significantly induce pulmonary fibrosis through increasing proinflammatory cytokine TGF-ß and histopathological changes.

Preparation and characterization of self-electrical stimuli conductive gellan based nano scaffold for nerve regeneration containing chopped short spun nanofibers of PVDF/MCM41 and polyaniline/graphene nanoparticles: Physical, mechanical and morphological studies.

Conductive self -electrical stimuli bioactive scaffolds could be used the potential for peripheral nerve regeneration with the maximum efficiency. To produce such conductive self-electrical stimuli bioactive scaffolds, chopped spun piezoelectric nanofibers of polyvinylidene fluoride/mesoporous silica nanoparticle (PVDF/MCM41) are prepared and incorporated in gellan/polyaniline/graphene (gellan/PAG) nanocomposites which have been previously prepared by incorporation of polyaniline/graphene (PAG) nanoparticles in gellan gel at 80 °C. Highly conductive binary doped polyaniline/graphene nanoparticles are prepared by chemical oxidative polymerization of aniline monomer using in-suite precipitation polymerization method in presence of graphene nanoparticles and sodium dodecyl sulfate. All intermediate and final products including spun PVDF/MCM41 nanofibers, PAG nanoparticles, and gellan-gelatin gel scaffolds containing PVDF/MCM41 nano spun fibers and PAG nanoparticles are characterized using different analysis methods. Chemical and structural analyses of PAG nanoparticles and PVDF/MCM41 nanofibers have been done using FTIR and XRD methods. The morphological structure of different samples is investigated using SEM. Morphological investigation and DLS results confirm fabrication of MCM41 nanoparticle with a completely spherical shape and the average size of 50 nm of which have been dispersed in electrospun PVDF nanofibers very well. Also, the preparation of PAG nanoparticle with high conductivity is verified with morphological and conductivity tests. MTT easy and biocompatibility test results indicate potential applicability of the prepared conductive self -stimuli nano-scaffold for nerve regeneration applications.

Differential Attachment of Pulmonary Cells on PDMS Substrate with Varied Features.

Cancer is now a global concern, and control of the function of cancer cells is recognized as an important challenge. Although many aggressive chemical and radiation methods are in practice to eliminate cancer cells, most of them imply severe adverse toxic effects on patients. Taking advantage of natural physical differences between cancer and normal cells might benefit the patient with more specific cytotoxicity and fewer adverse effects. Physical factors are the main means that can influence cell-biomaterial interaction. To explore the importance of attachment phenomena on cancer cells in this research, polydimethylsiloxane (PDMS) substrates with varied stiffness and roughness were synthesized and lung cancer cell's behavior on these surfaces was examined. To achieve diverse surface topography SDBD plasma was used at various exposure times, and different stiffness was obtained by changing in curing agent amount. Atomic force microscopy (AFM) and tensile modulus were employed to the characterization of roughness and stiffness respectively. Lung cancer cell survival and growth were studied by MTT and image processing analysis. The results indicated that softer and rougher surface made lung cancer cells to die. The number of detached cells, mean space of the detached cells, cellular coverage of surface, and the ratio of detached/ all cellular coverage were significantly affected by roughness and stiffness. Therefore, physical factors can control cell function, especially in lung cancer cells and these results might provide a strong base to help cancer cell removal.

Natural polymeric nanoparticles as a non-invasive probe for mesenchymal stem cell labelling.

Non-invasive tracking of stem cells after transplant is necessary for cell therapy and tissue engineering field. Herein, we introduce natural and biodegradable nanoparticle to develop a highly efficient nanoprobe with the ability to penetrate the stem cell for tracking. Based on the use of (Gd3+) to label stem cells for magnetic resonance imaging (MRI) we synthesized nanoparticle-containing Gd3+. Gd3+ could be used as t1-weighted MRI contrast agents. In this study, chitosan-alginate nanoparticles were synthesized as a clinical Dotarem® carrier for decreased t1-weighted. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR) were utilized for nanoprobe characterization and ICP analysis was performed for Gd3+ concentration measurement. The results illustrate that nanoprobes with spherical shape and with a size of 80 nm without any aggregation were obtained. Relaxivity results suggest that r1 in the phantom was 12.8 mM-1s-1 per Gd3+ ion, which is 3.5 times larger than that for Dotarem® (r1 ∼3.6 mM-1s-1 per Gd3+ ion) and this result for synthesized nanoprobe in stem cells 3.56 mM-1s-1 per Gd3+ ion with 2.16 times larger than that for Dotarem® was reported and also enhanced signal in in-vivo imaging was observed. Chitosan-alginate nanoparticles as a novel biocompatible probe for stem cell tracking can be utilized in tissue engineering approach.

New nanoprobe for breast cancer cell imaging based on low-density lipoprotein.

Many malignant cancers have an increased demand for lipoprotein due to the requirement for lipids for the rapid proliferation of the tumours and which is met by the increased availability of LDL through upregulation of LDL transporters. This unique phenomenon is the basis for the use of LDL based nanoparticles for cell imaging. In this study, a novel MR-active LDL nanoparticle was synthesised as the MRI probes. This MR-active LDL was characterised by using different techniques including scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier-transform infra-red spectroscopy (FTIR) and magnetic resonance imaging (MRI). The intracellular uptake of Gd3+ and cytotoxicity was measured by ICP-AES and MTT assay respectively. Results suggest that this nanoprobe with spherical shape and size of 55 nm has reduced relaxation time compared to commercial contrast agent and is introduced as an appropriate imaging probe. The amount of reabsorption of nanoprobe increased up to 6 h and given that the connection of the chelator does not have an effect on reabsorption proves that entry through transporter of APO section has done. This study lays the basis for exploring a personalised medicine strategy by directing a patient's own LDL to cancer cell imaging in the early stages.

Chitosan-alginate nano-carrier for transdermal delivery of pirfenidone in idiopathic pulmonary fibrosis.

Pirfenidone (PFD) is one of the pyridine family components with anti-inflammatory, antifibrotic effects and US FDA approved for the treatment of idiopathic pulmonary fibrosis (IPF). Presently, PFD is administered orally and this has setbacks. Hence, it is important to eliminate the pharmacotherapeutic limitations of PFD. This research was carried out to study the possibility of transdermal delivery of PFD using chitosan-sodium alginate nanogel carriers. In order to synthesize chitosan-sodium alginate nanoparticles loaded with PFD, the pre-gelation method was used. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR) analyses were used for the characterization. Drug encapsulation and release manner were studied using UV spectroscopy. Ex vivo permeation examinations were performed using Franz diffusion cell and fluorescence microscopy. The results showed that nanoparticles having spherical morphology and size in the range of 80 nm were obtained. In vitro drug release profile represents sustained release during 24 h, while 50% and 94% are the loading capacity and efficiency, respectively. Also, the skin penetration of PFD loaded in nanoparticles was significantly increased as compared to PFD solution. The obtained results showed that synthesized nanoparticles can be considered as promising carriers for PFD delivery.

Nanogel-based natural polymers as smart carriers for the controlled delivery of Timolol Maleate through the cornea for glaucoma.

Despite frequent scientific efforts, efficient ocular drug delivery is a major challenge for pharmaceutical scientists. Poor bioavailability of ophthalmic solutions can be overcome by using smart ophthalmic drug-delivery systems. In this research, loading and delivery of Timolol Maleate (TM) through the cornea by synthesized nanoparticles based on biopolymers (chitosan-alginate) were studied. The physico-chemical properties of these nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). Loading and release were evaluated by a UV-vis spectrometer and the ex vivo permeation study was carried out using the Franz Diffusion Cell and fluorescent microscopy studies. The results indicated that morphology and size of nanoparticles were spherical and in the range of 80-100nm. The loading capacity and encapsulation efficiency were about 42% and 94% respectively. They illustrated a burst release in the first hour followed by a slower and more sustained drug release during the next 24h. Also, the results indicated that the cornea penetration of TM loaded in nanoparticles was twice than that of TM. Hence, this nanocarrier can be considered as a suitable candidate for controlled TM delivery and release through the cornea.

Acute Toxicity Evaluation of Glycosylated Gd3+-Based Silica Nanoprobe.

PURPOSE: Early stage diseases diagnosed using magnetic resonance imaging (MRI) techniques is of high global interest as a potent noninvasive modality. MRI contrast agents are improved through modifications in structural and physicochemical properties of the applied nanoprobes. But, the potential toxic effects of nanoprobes upon exposure to biological systems are still a major concern. PROCEDURE: In this study, the acute toxicity of glycosylated Gd3+-based silica mesoporous nanospheres (GSNs) as a MRI contrast agent was evaluated in Balb/c mice. In order to evaluate in vivo toxicity of GSN, preclinical studies, daily weight monitoring, hematological/blood chemistry tests, and histological assessment were conducted. Magnetic resonance relaxivities of GSN was determined using a MRI scanner. RESULTS: The obtained results suggest that in vivo toxicity of GSN was mostly influenced by nanoparticle surface area, functionality, and nanoparticle zeta potential. The maximum tolerated dose (MTD) increased in the following order: mesoporous silica nanospheres (MSNs) at 1 mg/mice < GSN (aspect ratio 1, 2, 8) at 40 mg/mice. The results also indicate GSN, one of the best cell imaging contrast agent, which does not show any significant toxicity on multiple vital organs following injection of 20 mg/mice, while a significant T1-weighted enhancement was observed in whole body of a Balb/c mice 15 min postinjection of (5 µmol/kg) of body weight of GSN. CONCLUSIONS: These results shed light on the functionality of MSNs to minimize in vivo toxicity. Also, glyconanoprobe can be beneficially used for nanomedicine and cellular imaging applications without any significant toxicity.