Current Nanomedicine - Volume 8, Issue 1, 2018

Background: The silica-based nanomaterials are playing a major role to harnessing dual or multiple modalities in therapeutic and diagnostic applications. These silica- based materials are separately used as drug carrying substrate or contrast agents for magnetic resonance imaging (MRI). These materials are also used as a combined platform for both drug delivery and MRI contrast agents either as a T1- or T2- or combined T1- and T2- contrast agents for MRI image enhancement. This article presents an overview on the recent development of the ordered mesoporous silica nanoparticles (MSNs) and unordered non-MSNs silica nanoparticles used as MRI contrast agents, and describes their biological evaluations viz. biocompatibility, bio-toxicity, in vitro and in vivo MRI cell imaging, and MRI image enhancement in animals. Methods: Since the development of the silica-based MRI contrast agents started to grow from mid-2000, this review narrowly focusses on the pertinent articles published during the period of 2007 to 2016. Apparently, a large number of research articles reported the dual applications of silica materials both as a drug carrier for controlled release of drug and as a potential contrast agent for MRI image enhancement. This review has taken a structured approach by separately describing the design, development and applications of the MSNs-based materials being ordered in structure and the unordered non-MSNs silica nanoparticles as MRI contrast agents. The MSNs particularly contain Gd-based materials, and the non-MSNs silica nanoparticles contain Gd-, Fe-, and Mn-based materials. The biological evaluations of the MRI contrast agents containing MSNs and non-MSNs silica nanoparticles are also discussed. Results: The review reveals extensive diversities and complexities being involved in developing these materials. It discusses the types of contrast agents being developed; examinations of these materials for possible MRI contrast agents; their functionalities and mechanisms; in situ and in vivo MRI in cells and animals; and, a range of biological evaluations. The development of MRI contrast agents containing the non-MSNs such as, nanocomposites, nanocapsules and core-shell structured materials were associated with designs of enormous complexities where different synthetic techniques were applied such as, functionalising, grafting, tethering, coating and conjugating with polymers. Thus the properties of these developed materials significantly differed from each other. All the developed MRI contrast agents showed good biocompatibility, cell viability, and cell or cancer targeting specificity. Conclusion: Most of the commercially available MRI contrast agents representing the silica- based nanoparticles are found to be T1 contrast agents however, a few T2 contrast agents were also approved for clinical applications. The perspectives, insights and critical reflections on the stability, limitations, relaxivity and toxicity of the MRI contrast agents and, current and future developments of this area of research are presented. Thus, it is anticipated that the future researchers will be benefitted from the discussions presented in this review in understanding of the significance of these materials; a myriad range of complexities being involved in their developments; various implications; and, the future directions towards the development of more sophisticated silica-based MRI contrast agents.

Background: The introduction of new less invasive and non-invasive techniques for treating cardiac arrhythmias and neoplastic tissues has enhanced interest in medical imaging and iron oxide nanoparticles. The main scope of this review is to provide an overview on the usage of iron oxide nanoparticles (IONP) in magnetic resonance imaging (MRI) and thermal ablation. Methods: Several methods have been proposed to ablate abnormal growth and myocardial arrhythmia; namely surgical, radiofrequency, chemical and cryoablation. Fluoroscopy, multi-detector computed tomography, MRI as well as ultrasound are currently used for diagnosis and guiding therapies. Image-guided techniques help in visualizing the targets, precise delivering/verifying the treatment and follow up the prognosis. Results: Over one hundred papers were included in this review; the majority of the papers addressed the unique features of IONP and MRI settings. IONP have attracted special interest in MRI and thermal ablation due to their high relaxivity, biocompatibility, magnetic heating and low toxicity. The concept of ablation by magnetic nanoparticles is based on depositing magnetic nanoparticles in the tumor and their subsequent heating by an external alternating magnetic field. IONP have been used as: 1) MR contrast media for visualizing pathologic lesions before, during, and after ablation, 2) hyperthermal agents for generating heat during exposure to alternating magnetic field and 3) magnetic vectors (drugs and gene carriers) guided by magnetic field gradients to deliver therapies to pathologic lesions. IONP highlight ablated lesions in neighboring healthy tissue or organs due to improper targeting of lesions. It also enhances the vascular tree for proper catheter navigation. Conclusion: Iron oxide nanoparticles incorporate good biocompatibility and safety margin with their unique magnetic and thermic properties. IONP can be delivered locally and systemically (with caution). Furthermore, they blend diagnosis and treatment. The provision of pre-, during and post-ablation lesion characterization on IONP-contrast enhanced MRI might be helpful in complex ablation procedures and treatment.

Background: The development of nanostructures (nanoparticles and nanocapsules) is one of the most important pipelines of research of pharmaceutical technology. Methods: These nanotechnology pharmaceuticals allow the vectorization of drugs to tissues or cells target, allowing thus actions more specific and therapeutically active directed by molecules. Results: The use of molecules with an affinity for membrane receptors expressed in specific excess in tumor cells, monoclonal antibodies, or proteins, among others, is common for this purpose. In addition, these nanosystems allow to deliver drugs that could be the basis of the pharmacological treatment of many disorders of genetic origin in the future: biomolecules. Conclusion: The future scope of drug vectoring systems to target drug delivery using nanotechnologies can increase the control of pharmacokinetic parameters of chemotherapeutic agents.

Background: Algae are widely used for their beneficial properties by food, cosmetic and nutraceutical industry. For nutraceutical and cosmetic (e.g. oral and dermal) application, solubility is a key parameter. Algal extracts are available in sticky and completely dried form and in both cases it is difficult to formulate them due to solubility challenges. Therefore, attempts were made to produce stable algal nanosuspensions. A nano algal suspension could increase the biological activity (due to increased saturation solubility and higher dissolution velocity) and lead to better penetration or absorption profile. Methods: Dried algae products (N. oculata and Chaetoceros) were obtained from biotechnological cultivation. The algae were dispersed in Tween 80 or in Poloxamer 188 solutions and passed through a piston-gap high pressure homogenizer to produce nano algal suspensions. Production parameters like, number of homogenisation cycles, pressure etc, were optimised. Nanosuspensions were evaluated for particle size, zeta potential and crystallinity. Furthermore, nanosuspensions were converted to solid product using lyophilisation and extrusion-spheronisation technique. Results: A minimum size of about 226 nm could be achieved after 10 cycles at 1,500 bar. The aqueous nanosuspensions showed highest, but still insufficient stability at refrigeration (4 months data), decreasing stability with increasing temperature, especially at 50°C in the stress storage test and during autoclaving at 121°C. Preservation with Euxyl PE 9010 further decreased the physical stability of the aqueous algae nanosuspensions. Algae as natural material undergoes chemical degradation when in contact with water. For long-term preservation of the size and for chemical stabilization, the algae nanosuspensions were lyophilized. The algae nanoparticles re-dispersed well in water when using trehalose as cryoprotectant. The lyophilizate can be filled in capsules. Pellets were produced using the nanosuspensions as granulation fluid, filled in gelatine capsules for nutraceutical delivery. Conclusion: Nano-algal suspensions open new perspective for algae products with enhanced bioavailability and penetration profile. The produced nanosuspensions can be used for dermal, nutraceutical or cosmetics purposes.

Background: Maghemite nanoparticle is well known for its biocompatibility compared to other types of nanoparticles having huge biomedical applications. The aim of this study was to investigate the significance of maghemite nanoparticle and analyse the anti proliferative, oxidative stress and apoptosis potency of this on CRL-1739 Adenogastric carcinoma (AGS) cell line in order to understand its antitumor effect on gastric carcinoma. Methods: The cytotoxicity was examined by MTT assay and microscopic analysis on AGS cell line along with a small intestinal epithelial cell line IEC-6. The oxidative stress and cell damage on AGS were monitored by measuring the anti oxidants of glutathione S Transferase (GST), reduced glutathione (GSH) and trypan blue exclusion and Lactate dehydrogenase release (LDH) assay respectively. In addition live/dead assay, DNA fragmentation assay and semi quantitative PCR analysis were carried out. Results: The cytotoxicity results showed that significant growth inhibition was observed in the cancer cells compared to normal cells. The cytotoxicity resulted here was due to oxidative stress that reflected in the reduction of antioxidants and elevated levels of ROS and LDH. Moreover, it was investigated that nanoparticles arrested cell growth in the G2/M phase transition. The cell death mechanism induced by the nanoparticle upregulated the expression of apoptotic marker p53 along with down regulation of oncogene C-myc. Conclusion: The result obtained in this study suggests that the maghemite nanoparticle explode the activation of apoptosis in cancer cells by G2/M phase arrest as well as shows to be a potent targeted therapeutic agent.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by inflammatory activity, irreversible structural damage, and oxidative stress. Methotrexate (MTX) is widely used for RA management; however, MTX administration is associated with a decrease in the level of endogenous antioxidants. Co-administration of sesamol could combat oxidative stress alongside MTX regimen. The intent of the present study was to prepare, characterize, and evaluate the in vitro radical scavenging effects of novel mixed nanomicelles (NMs) of MTX co-encapsulated with an efficient natural antioxidant like sesamol. Methods: Novel MTX-sesamol loaded NMs (MTX-Ses-NMs) composed of phospholipid and sodium deoxycholate (SDC) were prepared by film hydration method and the micelle size, zeta potential, and entrapment efficiency (EE) was measured. Additionally, MTXSes- NMs were characterized for morphology, small-angle neutron scattering (SANS), structural features by Fourier Transform Infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (NMR), and X-ray diffraction (XRD) studies. The antiradical effects of MTX-Ses-NMs were evaluated by nitric oxide (NO) radical inhibition, hydroxyl radical, and superoxide anion radical scavenging assays. Results: MTX-Ses-NMs were fabricated successfully and the micelle size and zeta potential were found to be 123 ± 76 nm and -46.8 ± 16.4 mV, respectively. The encapsulation efficiency of MTX and sesamol in MTX-Ses-NMs was found to be 89.62 ± 1.58% and 86.77 ± 1.27%, respectively. Morphology study by transmission electron microscopy (TEM), and field emission gun scanning electron microscopy (FEG-SEM) corroborates the formation of NMs. FTIR, 1H NMR, and XRD studies validate the encapsulation of MTX and sesamol within the micelle core. Analysis of SANS data confirms the presence of micelles and showed a decrease in the thickness of micelles after drug loading. Moreover, in all the antiradical assays, MTX-Ses-NMs exhibited superior radical scavenging activity as compared to free MTX. Conclusion: The rationale of co-encapsulating sesamol with MTX was to augment the antiradical effects of the developed NMs and we achieved the improved antiradical status of NMs in vitro. The novel MTX-Ses-NMs might prove beneficial in reducing the toxic effects of MTX-induced oxidative stress in vivo.