Current challenges ahead in preparation, characterization, and pharmaceutical applications of nanoemulsions.

Nanoemulsions (NEs) are emulsions with particle size of less than around 100 nm. Reviewing the literature, several reports are available on NEs, including preparation, characterization, and applications of them. This review aims to brief challenges that researchers or formulators may encounter when working with NEs. For instance, when selecting NE components and identifying their concentrations, stability and safety of the preparation should be evaluated. When preparing an NE, issues over scale-up of the preparation as well as possible effects of the preparation process on the active ingredient need to be considered. When characterizing the NEs, the two major concerns are accuracy of the method and accessibility of the characterizing instrument. Also a highly efficient NE for clinical use to deliver the active ingredient to the target tissue with maximum safety profile is commonly sought. Throughout the review we also have tried to suggest approaches to overcome the challenges. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Polymeric nanoparticles for drug delivery in glioblastoma: State of the art and future perspectives.

Glioblastoma (GBM) is an aggressive, fatal and malignant primary brain tumor. Despite the current standard treatment for glioblastoma patients including neurosurgical resection, followed by concomitant radiation and chemotherapy, the median survival rate is only about 15 months. An unresolved challenge for current therapies is related to getting drugs through the blood-brain barrier (BBB), which hinders many chemotherapeutic agents from reaching tumors cells. Although a large amount of research has been done to circumvent the BBB and deliver drugs to the brain, with nanoparticles (NPs) taking the lead, the challenge is still high. In this regard, the BBB and how to transfer drug pathways through the BBB, especially using NPs, are introduced here. Afterwards, the latest advances in drug delivery, co-drug delivery, and combination modalities are described specifically for GBM treatments using natural and synthetic polymeric NPs and adjuvant therapies including hyperthermia, photodynamic therapy and also ketogenic regimens. In addition, receptor-mediated endocytosis agents that exist in endothelial capillary cells of the brain are explained. Lastly, future directions to finally deliver drugs through the BBB for GBM treatment are emphasized. It is the hope that this review can provide a number of practical pathways for the future development of BBB permeable nanochemotherapeutics against GBM.

Yogurt fortified with omega-3 using nanoemulsion containing flaxseed oil: Investigation of physicochemical properties.

Flaxseed oil as a natural ingredient has many health benefits due to the rich contents of omega-3 fatty acids. However, its use in food formulations is limited because of low aqueous solubility, easy oxidation owing to the unsaturated nature of the fatty acids such as omega-3. The aim of this study was to prepare a stable nanoemulsion containing flaxseed oil and investigate the fortification of yogurt with this nanoemulsion compared with fortification with bulk flaxseed oil. The nanoemulsion of flaxseed oil-in-water was obtained by low-energy emulsification method. Optimized nanoemulsion contains 3% (w/w) flaxseed vegetable oil, 36% (w/w) surfactant, 10% (w/w) co-surfactant, and 51% (w/w) deionized water as a continuous phase. The result of transmission electron microscopy (TEM) showed that the optimal size was about 60 nm, which was stayed stable for 11 months. The results of gas chromatography (GC) indicated that the amount of omega-3 in nanoemulsion containing flaxseed oil was 27.3% and 19.8% after 7 days and 11 months, respectively. The turbidity results indicated the transparency of nanoemulsion after 11 months as well. The results of centrifuge experiments and thermal stress cycles exhibited that the optimized nanoemulsion was physically stable without any sign of creaming, phase separation, and cracking. In addition, pH and acidity of the yogurt fortified with nanoemulsion containing flaxseed oil were 4.22 and 1.41 wt%, respectively. In conclusion, fortifying yogurt with the nanoemulsion containing flaxseed oil can be considered as a solution to increase solubility, bioavailability, and protection of omega-3.

Paclitaxel/methotrexate co-loaded PLGA nanoparticles in glioblastoma treatment: Formulation development and in vitro antitumor activity evaluation.

AIM: The aim of this study was to improve the therapeutic index of chemotherapeutic drugs on glioblastoma cells through an improved co-drug delivery system. MATERIALS AND METHODS: Methotrexate (MTX) and paclitaxel (PTX) were co-loaded into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with polyvinyl alcohol (PVA) and Poloxamer188 (P188). KEY FINDINGS: The mean size of the NPs was about 212 nm, with a zeta potential of about -15.7 mV. Encapsulation efficiency (EE%) and drug loading (DL%) were determined to be 72% and 4% for MTX and 85% and 4.9% for PTX, respectively. The prepared NPs were characterized by differential thermal analysis (DTA) and thermogravimetric analysis (TGA). Moreover, an in vitro sustained release profile was observed for both drug loaded PLGA NPs. Glioblastoma cellular uptake of the NPs was confirmed by fluorescence microscopy and cell survival rate was investigated through the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method after 48 h of incubation showing IC50 values of 24.5 µg·mL-1 for PTX and 9.5 µg·mL-1 for MTX for the MTX/PTX co-loaded PLGA nanoparticles coated with PVA/P188 (Co-2 NPs). Apoptosis and necrosis were also studied via flow cytometry, the lactate dehydrogenase (LDH) assay and the amount of anti-apoptotic protein (Bcl-2) expression. Blood compatibility of the co-delivery of PTX and MTX loaded PLGA NPs was investigated using a hemolysis method as well. SIGNIFICANCE: The co-delivery of PTX and MTX loaded PLGA NPs is promising for the treatment of glioblastoma compared to their respective free drug formulations and, thus, should be further investigated.

A Combinational Approach Towards Treatment of Breast Cancer: an Analysis of Noscapine-Loaded Polymeric Nanoparticles and Doxorubicin.

Our aim in this study was to clarify the combination anticancer effect of Noscapine (Nos) loaded in a polymeric nanocarrier with Doxorubicin (Dox) on breast cancer cells. Nanoprecipitation method was used to prepare methoxy polyethylene glycol (mPEG), poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) containing Nos. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to characterize the prepared Nos NPs. The anticancer activity of Nos NPs alone and in combination with Dox was assessed on 4T1 breast cancer cell line and in mice model. Spherical-shaped Nos NPs were prepared, with size of 101 ± 4.80 nm and zeta potential of - 15.40 ± 1 mV. Fourier transform infrared (FTIR) spectroscopy results demonstrated that Nos chemical structure was kept stable during preparation process. However, differential scanning calorimetric (DSC) thermogram proved that crystalline state of Nos changed to amorphous state in Nos NPs. The entrapment efficacy % (EE%) and drug loading % (DL%) of Nos NPs were about 87.20 ± 3.50% and 12.50 ± 2.30%, respectively. Synergistic anticancer effects of Nos both in free form (in hydrochloride form, Nos HCl) and Nos NPs form with Dox hydrochloride (Dox HCl) were observed on 4T1 cells. Combination of Nos NPs and Dox HCl inhibited tumor growth (68.50%) in mice more efficiently than Nos NPs (55.10%) and Dox HCl (32%) alone. Immunohistochemical (IHC) analysis of the tumor tissues confirmed antiangiogenic effect of Nos NPs. The findings highlighted efficacy of Nos NPs alone and in combination with Dox HCl on breast cancer tumors.

Investigation of Effective Parameters on Size of Paclitaxel Loaded PLGA Nanoparticles.

Purpose: The size of polymeric nanoparticles is considered as an effective factor in cancer therapy due to enterance into tumor tissue via the EPR effect. The purpose of this work was to investigate the effective parameters on poly(lactic-co-glycolic acid)-paclitaxel (PLGA -PTX) nanoparticles size. Methods: We prepared PLGA-PTX nanoparticles via single emulsion and precipitation methods with variable paremeters including drug concentration, aqueous to organic phase volume ratio, polymer concentration, sonication time and PVA concentration. Results: PLGA-PTX nanoparticles were characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM). The results exhibited that the diameter of nanoparticles enhanced with increasing drug, polymer and PVA concentrations whereas organic to aqueous phase volume ratio and sonication time required to the optimization for a given size. Conclusion: The precipitation method provides smaller nanoparticles compared to emulsion one. Variable parameters including drug concentration, aqueous to organic phase volume ratio, polymer concentration, sonication time and PVA concentration affect diameter of nanoparticles.

Biocompatibility and nanostructured materials: applications in nanomedicine.

There has been huge interest in applications of nanomaterials in biomedical science, including diagnosis, drug delivery, and development of human organs. Number of these nanomaterials has been already studied in human or at pre-clinical trial. There is a growing concern on potential toxicity and adverse effects of nanomaterials on human health, including lack of standard method of assessment of toxicology of these materials. Our investigation indicated that the bare and small nanoparticle have higher toxicity than modified and bulk materials, respectively. In addition, spherical nanoparticles have less toxicity than rod nanoparticles due to immune response of body.

Preparation and characterization of kefiran electrospun nanofibers.

In this study, we report the first successful production of kefiran nanofibers through electrospinning process using distilled water as solvent. For this purpose, kefiran was extracted from cultured kefir grains, and homogenous kefiran solutions with different concentrations were prepared and then electrospun to obtain uniform nanofibers. The effect of main process parameters, including applied voltage, tip-to-collector distance, and feeding rate, on diameter and morphology of produced nanofibers, was studied. Scanning electron microscopy (SEM) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were used to characterize electrospun mats. Rheological behavior of the kefiran solution was evaluated via a cone and plate rheometer too. The results exhibited that diameter of kefiran nanofibers increased with increasing polymer concentration, applied voltage, and polymer feeding rate, while tip-to-collector distance did not have significant effect on nanofiber diameter. ATR-FTIR spectra showed that kefiran has maintained its molecular structure during electrospinning process. Flow curves also demonstrated shear thinning behavior for kefiran solutions.