Displaying publications 41 - 60 of 182 in total

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  1. De Silva L, Fu JY, Htar TT, Muniyandy S, Kasbollah A, Wan Kamal WHB, et al.
    Int J Nanomedicine, 2019;14:1101-1117.
    PMID: 30863048 DOI: 10.2147/IJN.S184912
    Background and purpose: Niosomes are nonionic surfactant-based vesicles that exhibit certain unique features which make them favorable nanocarriers for sustained drug delivery in cancer therapy. Biodistribution studies are critical in assessing if a nanocarrier system has preferential accumulation in a tumor by enhanced permeability and retention effect. Radiolabeling of nanocarriers with radioisotopes such as Technetium-99m (99mTc) will allow for the tracking of the nanocarrier noninvasively via nuclear imaging. The purpose of this study was to formulate, characterize, and optimize 99mTc-labeled niosomes.

    Methods: Niosomes were prepared from a mixture of sorbitan monostearate 60, cholesterol, and synthesized D-α-tocopherol polyethylene glycol 1000 succinate-diethylenetriaminepentaacetic acid (synthesis confirmed by 1H and 13C nuclear magnetic resonance spectroscopy). Niosomes were radiolabeled by surface chelation with reduced 99mTc. Parameters affecting the radiolabeling efficiency such as concentration of stannous chloride (SnCl2·H2O), pH, and incubation time were evaluated. In vitro stability of radiolabeled niosomes was studied in 0.9% saline and human serum at 37°C for up to 8 hours.

    Results: Niosomes had an average particle size of 110.2±0.7 nm, polydispersity index of 0.229±0.008, and zeta potential of -64.8±1.2 mV. Experimental data revealed that 30 µg/mL of SnCl2·H2O was the optimal concentration of reducing agent required for the radiolabeling process. The pH and incubation time required to obtain high radiolabeling efficiency was pH 5 and 15 minutes, respectively. 99mTc-labeled niosomes exhibited high radiolabeling efficiency (>90%) and showed good in vitro stability for up to 8 hours.

    Conclusion: To our knowledge, this is the first study published on the surface chelation of niosomes with 99mTc. The formulated 99mTc-labeled niosomes possessed high radiolabeling efficacy, good stability in vitro, and show good promise for potential use in nuclear imaging in the future.

  2. Khames A, Khaleel MA, El-Badawy MF, El-Nezhawy AOH
    Int J Nanomedicine, 2019;14:2515-2531.
    PMID: 31040672 DOI: 10.2147/IJN.S190502
    Background: Fungal keratitis (FK) is a serious pathogenic condition usually associated with significant ocular morbidity. Natamycin (NAT) is the first-line and only medication approved by the Food and Drug Administration for the treatment of FK. However, NAT suffers from poor corneal penetration, which limits its efficacy for treating deep keratitis.

    Purpose: The objective of this work was to prepare NAT solid lipid nanoparticles (NAT-SLNs) to achieve sustained drug release and increased corneal penetration.

    Methods: NAT-SLNs were prepared using the emulsification-ultrasonication technique. Box- Behnken experimental design was applied to optimize the effects of independent processing variables (lipid concentration [X1], surfactant concentration [X2], and sonication frequency [X3]) on particle size (R1), zeta potential (ZP; R2), and drug entrapment efficiency (EE%) (R3) as responses. Drug release profile, ex vivo corneal permeation, antifungal susceptibility, and cytotoxicity of the optimized formula were evaluated.

    Results: The optimized formula had a mean particle size of 42 r.nm (radius in nanometers), ZP of 26 mV, and EE% reached ~85%. NAT-SLNs showed an extended drug release profile of 10 hours, with enhanced corneal permeation in which the apparent permeability coefficient (Papp) and steady-state flux (Jss) reached 11.59×10-2 cm h-1 and 3.94 mol h-1, respectively, in comparison with 7.28×10-2 cm h-1 and 2.48 mol h-1 for the unformulated drug, respectively. Antifungal activity was significantly improved, as indicated by increases in the inhibition zone of 8 and 6 mm against Aspergillus fumigatus ATCC 1022 and a Candida albicans clinical isolate, respectively, and minimum inhibitory concentration values that were decreased 2.5-times against both of these pathogenic strains. NAT-SLNs were found to be non-irritating to corneal tissue. NAT-SLNs had a prolonged drug release rate, that improved corneal penetration, and increased antifungal activity without cytotoxic effects on corneal tissues.

    Conclusion: Thus, NAT-SLNs represent a promising ocular delivery system for treatment of deep corneal keratitis.

  3. SreeHarsha N, Maheshwari R, Al-Dhubiab BE, Tekade M, Sharma MC, Venugopala KN, et al.
    Int J Nanomedicine, 2019;14:7419-7429.
    PMID: 31686814 DOI: 10.2147/IJN.S211224
    Background: Prostate cancer (PC) has the highest prevalence in men and accounts for a high rate of neoplasia-related death. Doxorubicin (DOX) is one of the most widely used anti-neoplastic drugs for prostate cancer among others. However, it has low specificity and many side effects and affects normal cells. More recently, there have been newly developed drug delivery tools which are graphene or graphene-based, used to increase the specificity of the delivered drug molecules. The graphene derivatives possess both π-π stacking and increased hydrophobicity, factors that increase the likelihood of drug delivery. Despite this, the hydrophilicity of graphene remains problematic, as it induced problems with stability. For this reason, the use of a chitosan coating remains one way to modify the surface features of graphene.

    Method: In this investigation, a hybrid nanoparticle that consisted of a DOX-loaded reduced graphene oxide that is stabilized with chitosan (rGOD-HNP) was developed.

    Result: The newly developed rGOD-HNP demonstrated high biocompatibility and efficiency in entrapping DOX (~65%) and releasing it in a controlled manner (~50% release in 48 h). Furthermore, it was also demonstrated that rGOD-HNP can intracellularly deliver DOX and more specifically in PC-3 prostate cancer cells.

    Conclusion: This delivery tool offers a feasible and viable method to deliver DOX photo-thermally in the treatment of prostate cancer.

  4. Wahgiman NA, Salim N, Abdul Rahman MB, Ashari SE
    Int J Nanomedicine, 2019;14:7323-7338.
    PMID: 31686809 DOI: 10.2147/IJN.S212635
    Background: Gemcitabine (GEM) is a chemotherapeutic agent, which is known to battle cancer but challenging due to its hydrophilic nature. Nanoemulsion is water-in-oil (W/O) nanoemulsion shows potential as a carrier system in delivering gemcitabine to the cancer cell.

    Methods: The behaviour of GEM in MCT/surfactants/NaCl systems was studied in the ternary system at different ratios of Tween 80 and Span 80. The system with surfactant ratio 3:7 of Tween 80 and Span 80 was chosen for further study on the preparation of nanoemulsion formulation due to the highest isotropic region. Based on the selected ternary phase diagram, a composition of F1 was chosen and used for optimization by using the D-optimal mixture design. The interaction variables between medium chain triglyceride (MCT), surfactant mixture Tween 80: Span 80 (ratio 3:7), 0.9 % sodium chloride solution and gemcitabine were evaluated towards particle size as a response.

    Results: The results showed that NaCl solution and GEM gave more effects on particle size, polydispersity index and zeta potential of 141.57±0.05 nm, 0.168 and -37.10 mV, respectively. The optimized nanoemulsion showed good stability (no phase separation) against centrifugation test and storage at three different temperatures. The in vitro release of gemcitabine at different pH buffer solution was evaluated. The results showed the release of GEM in buffer pH 6.5 (45.19%) was higher than GEM in buffer pH 7.4 (13.62%). The cytotoxicity study showed that the optimized nanoemulsion containing GEM induced cytotoxicity towards A549 cell and at the same time reduced cytotoxicity towards MRC5 when compared to the control (GEM solution).

  5. Ebadi M, Saifullah B, Buskaran K, Hussein MZ, Fakurazi S
    Int J Nanomedicine, 2019;14:6661-6678.
    PMID: 31695362 DOI: 10.2147/IJN.S214923
    Background: Cancer treatments are being continually developed. Increasingly more effective and better-targeted treatments are available. As treatment has developed, the outcomes have improved.

    Purpose: In this work, polyethylene glycol (PEG), layered double hydroxide (LDH) and 5-fluorouracil (5-FU) were used as a stabilizing agent, a carrier and an anticancer active agent, respectively.

    Characterization and methods: Magnetite nanoparticles (Fe3O4) coated with polyethylene glycol (PEG) and co-coated with 5-fluorouracil/Mg/Al- or Zn/Al-layered double hydroxide were synthesized by co-precipitation technique. Structural, magnetic properties, particle shape, particle size and drug loading percentage of the magnetic nanoparticles were investigated by XRD, TGA, FTIR, DLS, FESEM, TEM, VSM, UV-vis spectroscopy and HPLC techniques.

    Results: XRD, TGA and FTIR studies confirmed the formation of Fe3O4 phase and the presence of iron oxide nanoparticles, polyethylene glycol, LDH and the drug for all the synthesized samples. The size of the nanoparticles co-coated with Mg/Al-LDH is about 27 nm compared to 40 nm when they were co-coated with Zn/Al-LDH, with both showings near uniform spherical shape. The iron oxide nanoparticles retain their superparamagnetic property when they were coated with polyethylene glycol, polyethylene glycol co-coated with Mg/Al-LDH and polyethylene glycol co-coated with Zn/Al-LDH with magnetic saturation value of 56, 40 and 27 emu/g, respectively. The cytotoxicity study reveals that the anticancer nanodelivery system has better anticancer activity than the free drug, 5-FU against liver cancer HepG2 cells and at the same time, it was found to be less toxic to the normal fibroblast 3T3 cells.

    Conclusion: These are unique core-shell nanoparticles synthesized with the presence of multiple functionalities are hoped can be used as a multifunctional nanocarrier with the capability of targeted delivery using an external magnetic field and can also be exploited as hypothermia for cancer cells in addition to the chemotherapy property.

  6. Ashour AE, Badran M, Kumar A, Hussain T, Alsarra IA, Yassin AEB
    Int J Nanomedicine, 2019;14:9259-9273.
    PMID: 31819428 DOI: 10.2147/IJN.S223368
    Purpose: The main goal of this study is to evaluate the impact of physical incorporation of polyethylene glycol (PEG) into 5-fluorouracil (5-FU)-loaded polymeric nanoparticles (NPs).

    Methods: The 5-FU-loaded NPs were prepared utilizing a simple double emulsion method using polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA) with or without PEG 6000. The surface charge, particle size, and shape of NPs were evaluated by standard procedures. Both Fourier Transform Infrared Spectroscopy and X-ray diffraction spectra of the 5-FU loaded NPs were compared against the pure 5-FU. The in vitro release profile of 5-FU from the NPs was monitored by the dialysis tubing method. Cell death and apoptosis induction in response to 5-FU NP exposure were measured by MTT and Annexin-V/7-amino-actinomycin D (7-AAD) assays, respectively, in Daoy, HepG2, and HT-29 cancer cell lines.

    Results: The 5-FU loaded NPs were found to be spherical in shape with size ranging between 176±6.7 and 253.9±8.6 nm. The zeta potential varied between -7.13± 0.13 and -27.06±3.18 mV, and the entrapment efficiency was between 31.96% and 74.09%. The in vitro release of the drug followed a two-phase mode characterized by rapid release in the first 8 hrs followed by a period of slow release up to 72 hrs with composition-based variable extents. Cells exposed to NPs demonstrated a significant cell death which correlated with the ratio of PEG in the formulations in Daoy and HepG2 cells but not in HT-29 cells. Formulations (F1-F3) significantly induced early apoptosis in HT-29 cell lines.

    Conclusion: The physical PEGylation significantly enhanced the entrapment and loading efficiencies of 5-FU into NPs formulated with PLGA and PCL. It also fostered the in vitro cytotoxicity of 5-FU-loaded NPs in both Daoy and HepG2 cells. Induction of early apoptosis was confirmed for some of the formulations.

  7. Jiang H, Mani MP, Jaganathan SK
    Int J Nanomedicine, 2019;14:8149-8159.
    PMID: 31632024 DOI: 10.2147/IJN.S214646
    Introduction: Recently several new approaches were emerging in bone tissue engineering to develop a substitute for remodelling the damaged tissue. In order to resemble the native extracellular matrix (ECM) of the human tissue, the bone scaffolds must possess necessary requirements like large surface area, interconnected pores and sufficient mechanical strength.

    Materials and methods: A novel bone scaffold has been developed using polyurethane (PE) added with wintergreen (WG) and titanium dioxide (TiO2). The developed nanocomposites were characterized through field emission scanning electron microscopy (FESEM), Fourier transform and infrared spectroscopy (FTIR), X-ray diffraction (XRD), contact angle measurement, thermogravimetric analysis (TGA), atomic force microscopy (AFM) and tensile testing. Furthermore, anticoagulant assays, cell viability analysis and calcium deposition were used to investigate the biological properties of the prepared hybrid nanocomposites.

    Results: FESEM depicted the reduced fibre diameter for the electrospun PE/WG and PE/WG/TiO2 than the pristine PE. The addition of WG and TiO2 resulted in the alteration in peak intensity of PE as revealed in the FTIR. Wettability measurements showed the PE/WG showed decreased wettability and the PE/WG/TiO2 exhibited improved wettability than the pristine PE. TGA measurements showed the improved thermal behaviour for the PE with the addition of WG and TiO2. Surface analysis indicated that the composite has a smoother surface rather than the pristine PE. Further, the incorporation of WG and TiO2 improved the anticoagulant nature of the pristine PE. In vitro cytotoxicity assay has been performed using fibroblast cells which revealed that the electrospun composites showed good cell attachment and proliferation after 5 days. Moreover, the bone apatite formation study revealed the enhanced deposition of calcium content in the fabricated composites than the pristine PE.

    Conclusion: Fabricated nanocomposites rendered improved physico-chemical properties, biocompatibility and calcium deposition which are conducive for bone tissue engineering.

  8. Samrot AV, Sahithya CS, Selvarani A J, Pachiyappan S, Kumar S S
    Int J Nanomedicine, 2019;14:8105-8119.
    PMID: 31632021 DOI: 10.2147/IJN.S214236
    Background: Super-paramagnetic iron oxide nanoparticles (SPIONs) are widely used metal nanoparticles for various applications for its magnetic property and biocompatibility. In recent years, pollution of our environment especially with heavy metals in waterbodies has become a major threat and has left us very minimal sources of freshwater to drink. SPIONs or surface modified SPIONs can be used to remove these heavy metals.

    Methods: SPIONs were synthesized by co-precipitation method and further coated with a biopolymer, chitosan. Chromium solution was treated with the synthesized SPIONs to study the efficiency of chromium removal by surface adsorption. Later, the adsorption was analysed by direct and indirect analysis methods using UV-VIS spectrophotometry and isotherm studies.

    Results: Stable chitosan-coated SPIONs were synthesized and they adsorbed chromium better than the uncoated SPIONs, where it was adsorbing up to 100 ppm. Adsorption was found to be increasing with decrease in pH.

    Conclusion: The surface-modified SPIONs expressed cumulative adsorption action. Even after the adsorption studies, chitosan-coated SPIONs were possessing magnetic property. Thus, the surface-modified SPIONs can become an ideal nanotechnology tool to remove the chromium from groundwater.

  9. Jahangirian H, Kalantari K, Izadiyan Z, Rafiee-Moghaddam R, Shameli K, Webster TJ
    Int J Nanomedicine, 2019;14:1633-1657.
    PMID: 30880970 DOI: 10.2147/IJN.S184723
    Conventional cancer treatment techniques show several limitations including low or no specificity and consequently a low efficacy in discriminating between cancer cells and healthy cells. Recent nanotechnology developments have introduced smart and novel therapeutic nanomaterials that take advantage of various targeting approaches. The use of nanotechnology in medicine and, more specifically, drug delivery is set to spread even more rapidly than it has over the past two decades. Currently, many nanoparticles (NPs) are under investigation for drug delivery including those for cancer therapy. Targeted nanomaterials bind selectively to cancer cells and greatly affect them with only a minor effect on healthy cells. Gold nanoparticles (Au-NPs), specifically, have been identified as significant candidates for new cancer therapeutic modalities because of their biocompatibility, easy functionalization and fabrication, optical tunable characteristics, and chemophysical stability. In the last decade, there has been significant research on Au-NPs and their biomedical applications. Functionalized Au-NPs represent highly attractive and promising candidates for drug delivery, owing to their unique dimensions, tunable surface functionalities, and controllable drug release. Further, iron oxide NPs due to their "superparamagnetic" properties have been studied and have demonstrated successful employment in numerous applications. In targeted drug delivery systems, drug-loaded iron oxide NPs can accumulate at the tumor site with the aid of an external magnetic field. This can lead to incremental effectiveness in drug release to the tumor site and vanquish cancer cells without harming healthy cells. In order for the application of iron oxide NPs in the human body to be realized, they should be biodegradable and biocompatible to minimize toxicity. This review illustrates recent advances in the field drug and small molecule delivery such as fluorouracil, folic acid, doxorubicin, paclitaxel, and daunorubicin, specifically when using gold and iron oxide NPs as carriers of anticancer therapeutic agents.
  10. Sisin NNT, Abdul Razak K, Zainal Abidin S, Che Mat NF, Abdullah R, Ab Rashid R, et al.
    Int J Nanomedicine, 2019;14:9941-9954.
    PMID: 31908451 DOI: 10.2147/IJN.S228919
    Purpose: The aim of this study was to investigate the potential of the synergetic triple therapeutic combination encompassing bismuth oxide nanoparticles (BiONPs), cisplatin (Cis), and high dose rate (HDR) brachytherapy with Ir-192 source in breast cancer and normal fibroblast cell line.

    Methods: In vitro models of breast cancer cell lines (MCF-7, MDA-MB-231) and normal fibroblast cell line (NIH/3T3) were employed. Cellular localization and cytotoxicity studies were conducted prior to inspection on the radiosensitization effects and generation of reactive oxygen species (ROS) on three proposed radiosensitizers: BiONPs, Cis, and BiONPs-Cis combination (BC). The optimal, non-cytotoxic concentration of BiONPs (0.5 mM) and the 25% inhibitory concentration of Cis (1.30 µM) were applied. The radiosensitization effects were evaluated by using a 0.38 MeV Iridium-192 HDR brachytherapy source over a prescribed dose range of 0 Gy to 4 Gy.

    Results: The cellular localization of BiONPs was visualized by light microscopy and accumulation of the BiONPs within the vicinity of the nuclear membrane was observed. Quantification of the sensitization enhancement ratio extrapolated from the survival curves indicates radiosensitization effects for MCF-7 and MDA-MB-231 when treated with BiONPs, Cis, and BC. However, NIH/3T3 cells exhibited contradictive behavior as it only reacted towards the BC combination. Nonetheless, the MCF-7 cell line loaded with BC shows the highest SER of 4.29. ROS production analysis, on the other hand, shows that Cis and BC radiosensitizers generated the highest free radicals in comparison to BiONPs alone.

    Conclusion: A BiONPs-Cis combination was unveiled as a novel approach that offers promising radiosensitization enhancement that will increase the efficiency of tumor control while preserving the normal tissue at a reduced dose. This data is the first precedent to prove the synergetic implication of BiONPs, Cis, and HDR brachytherapy that will be beneficial for future chemoradiotherapy strategies in cancer care.

  11. Yusof F, Sha'ban M, Azhim A
    Int J Nanomedicine, 2019;14:5491-5502.
    PMID: 31410000 DOI: 10.2147/IJN.S207270
    PURPOSE: Meniscus is a fibrocartilagenous tissue that cannot effectively heal due to its complex structure and presence of avascular zone. Thus, tissue engineering and regenerative medicine offer an alternative for the regeneration of meniscus tissues using bioscaffolds as a replacement for the damaged one. The aim of this study was to prepare an ideal meniscus bioscaffold with minimal adverse effect on extracellular matrix components (ECMs) using a sonication treatment system.

    METHODS: The decellularization was achieved using a developed closed sonication treatment system for 10 hrs, and continued with a washing process for 5 days. For the control, a simple immersion treatment was set as a benchmark to compare the decellularization efficiency. Histological and biochemical assays were conducted to investigate the cell removal and retention of the vital extracellular matrix. Surface ultrastructure of the prepared scaffolds was evaluated using scanning electron microscope at 5,000× magnification viewed from cross and longitudinal sections. In addition, the biomechanical properties were investigated through ball indentation testing to study the stiffness, residual forces and compression characteristics. Statistical significance between the samples was determined with p-value =0.05.

    RESULTS: Histological and biochemical assays confirmed the elimination of antigenic cellular components with the retention of the vital extracellular matrix within the sonicated scaffolds. However, there was a significant removal of sulfated glycosaminoglycans. The surface histoarchitecture portrayed the preserved collagen fibril orientation and arrangement. However, there were minor disruptions on the structure, with few empty micropores formed which represented cell lacunae. The biomechanical properties of bioscaffolds showed the retention of viscoelastic behavior of the scaffolds which mimic native tissues. After immersion treatment, those scaffolds had poor results compared to the sonicated scaffolds due to the inefficiency of the treatment.

    CONCLUSION: In conclusion, this study reported that the closed sonication treatment system had high capabilities to prepare ideal bioscaffolds with excellent removal of cellular components, and retained extracellular matrix and biomechanical properties.

  12. Ge Y, Lakshmipriya T, Gopinath SC, Anbu P, Chen Y, Hariri F, et al.
    Int J Nanomedicine, 2019;14:7851-7860.
    PMID: 31632005 DOI: 10.2147/IJN.S222238
    BACKGROUND: Gestational diabetes mellitus is a commonly occurring metabolic disorder during pregnancy, affecting >4% of pregnant women. It is generally defined as the intolerance of glucose with the onset or initial diagnosis during pregnancy. This illness affects the placenta and poses a threat to the baby as it affects the supply of proper oxygen and nutrients.

    PURPOSE: Due to the high percentage of affected pregnant women, it should be mandatory to evaluate glucose levels during pregnancy and there is a need for a continuous monitoring system.

    METHODS: Herein, the investigators modified the interdigitated (di)electrodes (IDE) sensing surface to detect the glucose on covalently immobilized glucose oxidase (GOx) with the graphene. The characterization of graphene and gold nanoparticle (GNP) was performed by high-resolution microscopy.

    RESULTS: Sensitivity was found to be 0.06 mg/mL and to enhance the detection, GOx was complexed with GNP. GNP-GOx was improved the sensitive detection twofold from 0.06 to 0.03 mg/mL, and it also displayed higher levels of current changes at all the concentrations of glucose that were tested. High-performance of the above IDE sensing system was attested by the specificity, reproducibility and higher sensitivity detections. Further, the linear regression analysis indicated the limit of detection to be between 0.02 and 0.03 mg/mL.

    CONCLUSION: This study demonstrated the potential strategy with nanocomposite for diagnosing gestational diabetes mellitus.

  13. Wang F, Gopinath SC, Lakshmipriya T
    Int J Nanomedicine, 2019;14:8469-8481.
    PMID: 31695375 DOI: 10.2147/IJN.S219976
    BACKGROUND: A pandemic influenza viral strain, influenza A/California/07/2009 (pdmH1N1), has been considered to be a potential issue that needs to be controlled to avoid the seasonal emergence of mutated strains.

    MATERIALS AND METHODS: In this study, aptamer-antibody complementation was implemented on a multiwalled carbon nanotube-gold conjugated sensing surface with a dielectrode to detect pandemic pdmH1N1. Preliminary biomolecular and dielectrode surface analyses were performed by molecular and microscopic methods. A stable anti-pdmH1N1 aptamer sequence interacted with hemagglutinin (HA) and was compared with the antibody interaction. Both aptamer and antibody attachments on the surface as the basic molecule attained the saturation at nanomolar levels.

    RESULTS: Aptamers were found to have higher affinity and electric response than antibodies against HA of pdmH1N1. Linear regression with aptamer-HA interaction displays sensitivity in the range of 10 fM, whereas antibody-HA interaction shows a 100-fold lower level (1 pM). When sandwich-based detection of aptamer-HA-antibody and antibody-HA-aptamer was performed, a higher response of current was observed in both cases. Moreover, the detection strategy with aptamer clearly discriminated the closely related HA of influenza B/Tokyo/53/99 and influenza A/Panama/2007/1999 (H3N2).

    CONCLUSION: The high performance of the abovementioned detection methods was supported by the apparent specificity and reproducibility by the demonstrated sensing system.

  14. Geetha Bai R, Muthoosamy K, Manickam S, Hilal-Alnaqbi A
    Int J Nanomedicine, 2019;14:5753-5783.
    PMID: 31413573 DOI: 10.2147/IJN.S192779
    Tissue engineering embraces the potential of recreating and replacing defective body parts by advancements in the medical field. Being a biocompatible nanomaterial with outstanding physical, chemical, optical, and biological properties, graphene-based materials were successfully employed in creating the perfect scaffold for a range of organs, starting from the skin through to the brain. Investigations on 2D and 3D tissue culture scaffolds incorporated with graphene or its derivatives have revealed the capability of this carbon material in mimicking in vivo environment. The porous morphology, great surface area, selective permeability of gases, excellent mechanical strength, good thermal and electrical conductivity, good optical properties, and biodegradability enable graphene materials to be the best component for scaffold engineering. Along with the apt microenvironment, this material was found to be efficient in differentiating stem cells into specific cell types. Furthermore, the scope of graphene nanomaterials in liver tissue engineering as a promising biomaterial is also discussed. This review critically looks into the unlimited potential of graphene-based nanomaterials in future tissue engineering and regenerative therapy.
  15. Qi J, Zhang H, Wang Y, Mani MP, Jaganathan SK
    Int J Nanomedicine, 2018;13:2777-2788.
    PMID: 29785105 DOI: 10.2147/IJN.S151242
    Introduction: Currently, the design of extracellular matrix (ECM) with nanoscale properties in bone tissue engineering is challenging. For bone tissue engineering, the ECM must have certain properties such as being nontoxic, highly porous, and should not cause foreign body reactions.

    Materials and methods: In this study, the hybrid scaffold based on polyvinyl alcohol (PVA) blended with metallocene polyethylene (mPE) and plectranthus amboinicus (PA) was fabricated for bone tissue engineering via electrospinning. The fabricated hybrid nanocomposites were characterized by scanning electron microscopy (SEM), Fourier transform and infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), contact angle measurement, and atomic force microscopy (AFM). Furthermore, activated partial thromboplastin time (APTT), prothrombin time (PT), and hemolytic assays were used to investigate the blood compatibility of the prepared hybrid nanocomposites.

    Results: The prepared hybrid nanocomposites showed reduced fiber diameter (238±45 nm) and also increased porosity (87%) with decreased pore diameter (340±86 nm) compared with pure PVA. The interactions between PVA, mPE, and PA were identified by the formation of the additional peaks as revealed in FTIR. Furthermore, the prepared hybrid nanocomposites showed a decreased contact angle of 51°±1.32° indicating a hydrophilic nature and exhibited lower thermal stability compared to pristine PVA. Moreover, the mechanical results revealed that the electrospun scaffold showed an improved tensile strength of 3.55±0.29 MPa compared with the pristine PVA (1.8±0.52 MPa). The prepared hybrid nanocomposites showed delayed blood clotting as noted in APTT and PT assays indicating better blood compatibility. Moreover, the hemolysis assay revealed that the hybrid nanocomposites exhibited a low hemolytic index of 0.6% compared with pure PVA, which was 1.6% suggesting the safety of the developed nanocomposite to red blood cells (RBCs).

    Conclusion: The prepared nanocomposites exhibited better physico-chemical properties, sufficient porosity, mechanical strength, and blood compatibility, which favors it as a valuable candidate in bone tissue engineering for repairing the bone defects.

  16. Harun SN, Nordin SA, Gani SSA, Shamsuddin AF, Basri M, Basri HB
    Int J Nanomedicine, 2018;13:2571-2584.
    PMID: 29731632 DOI: 10.2147/IJN.S151788
    Background and aim: Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood-brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered.

    Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties.

    Results: The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of -46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0-
    t
    , prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0-
    t
    , prolonged half-life, and lower clearance as compared to free cefuroxime solution.

    Conclusion: Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.

  17. Xia N, Deng D, Wang Y, Fang C, Li SJ
    Int J Nanomedicine, 2018;13:2521-2530.
    PMID: 29731627 DOI: 10.2147/IJN.S154046
    Background: Prostate-specific antigen (PSA), a serine protease, is a biomarker for preoperative diagnosis and screening of prostate cancer and monitoring of its posttreatment.

    Methods: In this work, we reported a colorimetric method for clinical detection of PSA using gold nanoparticles (AuNPs) as the reporters. The method is based on ascorbic acid (AA)-induced in situ formation of AuNPs and Cu2+-catalyzed oxidation of AA. Specifically, HAuCl4 can be reduced into AuNPs by AA; Cu2+ ion can catalyze the oxidation of AA by O2 to inhibit the formation of AuNPs. In the presence of the PSA-specific peptide (DAHSSKLQLAPP)-modified gold-coated magnetic microbeads (MMBs; denoted as DAHSSKLQLAPP-MMBs), complexation of Cu2+ by the MMBs through the DAH-Cu2+ interaction depressed the catalyzed oxidation of AA and thus allowed for the formation of red AuNPs. However, once the peptide immobilized on the MMB surface was cleaved by PSA, the DAHSSKLQ segment would be released. The resultant LAPP fragment remaining on the MMB surface could not sequestrate Cu2+ to depress its catalytic activity toward AA oxidation. Consequently, no or less AuNPs were generated.

    Results: The linear range for PSA detection was found to be 0~0.8 ng/mL with a detection limit of 0.02 ng/mL. Because of the separation of cleavage step and measurement step, the interference of matrix components in biological samples was avoided.

    Conclusion: The high extinction coefficient of AuNPs facilitates the colorimetric analysis of PSA in serum samples. This work is helpful for designing of other protease biosensors by matching specific peptide substrates.

  18. Moniri M, Boroumand Moghaddam A, Azizi S, Abdul Rahim R, Zuhainis Saad W, Navaderi M, et al.
    Int J Nanomedicine, 2018;13:2955-2971.
    PMID: 29861630 DOI: 10.2147/IJN.S159637
    Background: Molecular investigation of wound healing has allowed better understanding about interaction of genes and pathways involved in healing progression.

    Objectives: The aim of this study was to prepare magnetic/bacterial nanocellulose (Fe3O4/BNC) nanocomposite films as ecofriendly wound dressing in order to evaluate their physical, cytotoxicity and antimicrobial properties. The molecular study was carried out to evaluate expression of genes involved in healing of wounds after treatment with BNC/Fe3O4 films.

    Study design materials and methods: Magnetic nanoparticles were biosynthesized by using Aloe vera extract in new isolated bacterial nanocellulose (BNC) RM1. The nanocomposites were characterized using X-ray diffraction, Fourier transform infrared, and field emission scanning electron microscopy. Moreover, swelling property and metal ions release profile of the nanocomposites were investigated. The ability of nanocomposites to promote wound healing of human dermal fibroblast cells in vitro was examined. Bioinformatics databases were used to identify genes with important healing effect. Key genes which interfered with healing were studied by quantitative real time PCR.

    Results: Spherical magnetic nanoparticles (15-30 nm) were formed and immobilized within the structure of BNC. The BNC/Fe3O4 was nontoxic (IC50>500 μg/mL) with excellent wound healing efficiency after 48 hours. The nanocomposites showed good antibacterial activity ranging from 6±0.2 to 13.40±0.10 mm against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa. The effective genes for the wound healing process were TGF-B1, MMP2, MMP9, Wnt4, CTNNB1, hsa-miR-29b, and hsa-miR-29c with time dependent manner. BNC/Fe3O4 has an effect on microRNA by reducing its expression and therefore causing an increase in the gene expression of other genes, which consequently resulted in wound healing.

    Conclusion: This eco-friendly nanocomposite with excellent healing properties can be used as an effective wound dressing for treatment of cutaneous wounds.

  19. Megat Nabil Mohsin S, Hussein MZ, Sarijo SH, Fakurazi S, Arulselvan P, Taufiq-Yap YH
    Int J Nanomedicine, 2018;13:6359-6374.
    PMID: 30349255 DOI: 10.2147/IJN.S171390
    Introduction: The potential of layered double hydroxide (LDH) as a host of multiple ultraviolet-ray absorbers was investigated by simultaneous intercalation of benzophenone 4 (B4) and Eusolex® 232 (EUS) in Zn/Al LDH.

    Methods: The nanocomposites were prepared via coprecipitation method at various molar ratios of B4 and EUS.

    Results: At equal molar ratios, the obtained nanocomposite showed an intercalation selectivity that is preferential to EUS. However, the selectivity ratio of intercalated anions was shown to be capable of being altered by adjusting the molar ratio of intended guests during synthesis. Dual-guest nanocomposite synthesized with B4:EUS molar ratio 3:1 (ZEB [3:1]) showed an intercalation selectivity ratio of B4:EUS =53:47. Properties of ZEB (3:1) were monitored using powder X-ray diffractometer to show a basal spacing of 21.8 Å. Direct-injection mass spectra, Fourier transform infrared spectra, and ultraviolet-visible spectra confirmed the dual intercalation of both anions into the interlayer regions of dual-guest nanocomposite. The cytotoxicity study of dual-guest nanocomposite ZEB (3:1) on human dermal fibroblast cells showed no significant toxicity until 25 μg/mL.

    Conclusion: Overall, the findings demonstrate successful customization of ultraviolet-ray absorbers composition in LDH host.

  20. Dhand C, Balakrishnan Y, Ong ST, Dwivedi N, Venugopal JR, Harini S, et al.
    Int J Nanomedicine, 2018;13:4473-4492.
    PMID: 30122921 DOI: 10.2147/IJN.S159770
    Introduction: In search for cross-linkers with multifunctional characteristics, the present work investigated the utility of quaternary ammonium organosilane (QOS) as a potential cross-linker for electrospun collagen nanofibers. We hypothesized that the quaternary ammonium ions improve the electrospinnability by reducing the surface tension and confer antimicrobial properties, while the formation of siloxane after alkaline hydrolysis could cross-link collagen and stimulate cell proliferation.

    Materials and methods: QOS collagen nanofibers were electrospun by incorporating various concentrations of QOS (0.1%-10% w/w) and were cross-linked in situ after exposure to ammonium carbonate. The QOS cross-linked scaffolds were characterized and their biological properties were evaluated in terms of their biocompatibility, cellular adhesion and metabolic activity for primary human dermal fibroblasts and human fetal osteoblasts.

    Results and discussion: The study revealed that 1) QOS cross-linking increased the flexibility of otherwise rigid collagen nanofibers and improved the thermal stability; 2) QOS cross-linked mats displayed potent antibacterial activity and 3) the biocompatibility of the composite mats depended on the amount of QOS present in dope solution - at low QOS concentrations (0.1% w/w), the mats promoted mammalian cell proliferation and growth, whereas at higher QOS concentrations, cytotoxic effect was observed.

    Conclusion: This study demonstrates that QOS cross-linked mats possess anti-infective properties and confer niches for cellular growth and proliferation, thus offering a useful approach, which is important for hard and soft tissue engineering and regenerative medicine.

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