Preparation,characterization, and evaluation of amino acid modified magnetic nanoparticles: drug delivery and MRI contrast agent applications

Abstract

This study is a report about the synthesis iron oxide magnetic nanoparticles (IONPs) which modified with positive and negative charged amino acids (AAs). l-Arginine (Arg) and l-aspartic acid (Asp) which have of guanidinium and carboxylic acid groups, respectively, were selected for this study. After loading chrysin in amino acids modified iron oxide magnetic nanoparticles (F@AAs@Chrysin NPs), it was characterized by XRD, TGA, FTIR, VSM, and TEM techniques. Finally, MTT assays on HFF-2 and HEK-293 cell lines were performed for determination of biocompatibility of AA coated IONPs. The results show that, the ζ-potential and average size of F@Arg@chrysin NPs and F@Asp@chrysin NPs were to ?3.87, ?2.12?mV, 18.75?±?2.40 (mean?±?SD (n?=?50)) nm, and 19.86?±?2.22 (mean?±?SD (n?=?48)) nm, respectively. Also, the results indicated that these F@AAs@Chrysin NPs were appropriate for delivery of chrysin. Furthermore, the phantom MRI studies showed the IONPs can be used as contrast agent for the revealing of tumor.     

Fabrication of long-acting insulin formulation based on poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles: preparation,optimization, characterization,and in vitro evaluation

The purpose of this research was the fabrication, statistical optimization, and in vitro characterization of insulin-loaded poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles (INS-PHBV-NPs). Nanopar-ticles were successfully developed by double emulsification solvent evaporation method. The NPs were characterized for particle size, entrapment efficiency (EE%), and polydispersity index (PDI). The NPs also were characterized by scanning electron microscopy (SEM), Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and circular dichroism (CD). The optimum conditions were found to be 1.6% polyvinyl alcohol (PVA), 0.9% of PHBV, and 15?mg/ml of insulin with the aid of the Box–Behnken experimental design results. The optimized NPs showed spherical shape with particle size of 250.21?±?11.37?nm, PDI of 0.12?±?0.01, and with EE% of 90.12?±?2.10%. In vitro drug release pattern followed Korsmeyer–Peppas model and exhibited an initial burst release of 19% with extended drug release of 63.2% from optimized NPs within 27?d. In conclusion, these results suggest that INS-PHBV-NPs could be a promising candidate for designing an injectable sustained release formulation for insulin.     

Preparation and evaluation of nanoparticles loading plasmid DNAs inserted with siRNA fragments targeting c-Myc gene

Context: c-Myc plays a key role in glioma cancer stem cell maintenance. A drug delivery system, nanoparticles loading plasmid DNAs inserted with siRNA fragments targeting c-Myc gene (NPs-c-Myc-siRNA-pDNAs), for the treatment of glioma, has not previously been reported.

Objective: NPs-c-Myc-siRNA-pDNAs were prepared and evaluated in vitro.

Materials and methods: Three kinds of c-Myc-siRNA fragments were separately synthesized and linked with empty siRNA expression vectors in the mole ratio of 3:1 by T4 DNA ligase. The linked products were then separately transfected into Escherichia coli. DH5α followed by extraction with Endofree plasmid Mega kit (Qiagen, Hilden, Germany) obtained c-Myc-siRNA-pDNAs. Finally, the recombinant c-Myc-siRNA3-pDNAs, generating the highest transfection efficiency and the greatest apoptotic ability, were chosen for encapsulation into NPs by the double-emulsion solvent-evaporation procedure, followed by stability, transfection efficiency, as well as qualitative and quantitative apoptosis evaluation.

Results: NPs-c-Myc-siRNA3-pDNAs were obtained with spherical shape in uniform size below 150?nm, with the zeta potential about ?18?mV, the encapsulation efficiency and loading capacity as 76.3?±?5.4% and 1.91?±?0.06%, respectively. The stability results showed that c-Myc-siRNA3-pDNAs remained structurally and functionally stable after encapsulated into NPs, and NPs could prevent the loaded c-Myc-siRNA3-pDNAs from DNase degradation. The transfection efficiency of NPs-c-Myc-siRNA3-pDNAs was proven to be positive. Furthermore, NPs-c-Myc-siRNA3-pDNAs produced significant apoptosis with the apoptotic rate at 24.77?±?5.39% and early apoptosis cells observed.

Discussion and conclusion: Methoxy-poly-(ethylene-glycol)-poly-(lactide-co-glycolide) nanoparticles (MPEG–PLGA-NPs) are potential delivery carriers for c-Myc-siRNA3-pDNAs.     

Preparation and characterization of insulin chitosan-nanoparticles loaded in buccal films

Chitosan nanoparticles loaded with insulin (IN-CS-NPs) were prepared using ionic gelation method using sodium tripolyphophate as a crosslinker. Later the nanoparticles (NPs) were dispersed in buccal films. The physicochemical properties and the morphology of the nanoparticles were characterized. The stability and release of insulin from the NPs were investigated. Buccal films were prepared separately and their properties such as the weight, thickness, pH, and mucoadhesiveness were investigated. The best film was used to disperse IN-CS-NPs and the loaded film was characterized. The nanoparticles size, polydispersity index, zeta potential, entrapment efficacy, and the loading capacity were 325.07?±?1.32?nm, 0.38?±?0.03 and 8.41?±?0.80?mV, and 73.27 and 18.03%, respectively. The weight and thickness of the loaded film with IN-CS-NPs were 23.0?±?3.0?mg and 0.32?±?0.04?mm, respectively and the mucoadhesive force was 2.3?±?0.2 N. The drug was stable in the NPs and in the films for three months, and its release was controlled by the film and the nanoparticles. Finally, the films loaded with IN-CS-NPs were studied in vivo and were compared to the commercially available insulin. The films prepared in this work were found to decrease glucose level significantly in diabetic rats.     

Gel network comprising UV crosslinked PLGA-b-PEG-MA nanoparticles for ibuprofen topical delivery

Ibuprofen is a non-steroidal anti-inflammatory drug for the treatment of Rheumatoid Arthritis and osteoarthritis. In this study, we prepared topical gel network for enhancement of ibuprofen penetration, maintenance of controlled release and increased patient compliance. Nanoparticles containing ibuprofen were prepared by means of emulsion formation/solvent diffusion method using synthesized copolymer. Nanoparticles were then conjugated with aminoethylmethacrylate, resulting in ibuprofen-loaded nanoparticles in PLGA-b-PEG-MA structure. Ibuprofen-loaded gel networks were developed by crosslinking nanoparticles via UV exposure. Suitability for topical application has been assessed through characterization of particle size, zeta potential, morphology, encapsulation efficiency, in vitro release, cytotoxicity and enhancement of in vitro wound healing. The mean diameter of nanoparticles was measured as 230?±?20?nm. Gel network formulations with higher particle size (2800?±?350?nm) and zeta potential (39.8?±?9.2?mV), depending on conjugation of methacrylate within copolymeric structure, and having encapsulation efficacy of 73.6?±?2.8% were prepared. The in vitro release of ibuprofen was sustained for more than 7?hours. Gel network improved collagen synthesis, type I collagen mRNA expression and fibrosis in dose dependent manner. Based on this, we can conclude that PLGA-b-PEG gel network might be a promising systems for the local delivery of ibuprofen in RA patients.     

Nose-to-brain delivery of temozolomide-loaded PLGA nanoparticles functionalized with anti-EPHA3 for glioblastoma targeting

Glioblastoma is the most common malignant brain tumor. Efficient delivery of drugs targeting glioblastomas remains a challenge. Ephrin type-A receptor 3 (EPHA3) tyrosine kinase antibody-modified polylactide-co-glycolide (PLGA) nanoparticles (NPs) were developed to target glioblastoma via nose-to-brain delivery. Anti-EPHA3-modified, TBE-loaded NPs were prepared using an emulsion-solvent evaporation method, showed a sustained in vitro release profile up to 48 h and a mean particle size of 145.9 ± 8.7 nm. The cellular uptake of anti-EPHA3-modified NPs by C6 cells was significantly enhanced compared to that of nontargeting NPs (p < .01). In vivo imaging and distribution studies on the glioma-bearing rats showed that anti-EPHA3-modified NPs exhibited high fluorescence intensity in the brain and effectively accumulated to glioma tissues, indicating the targeting effect of anti-EPHA3. Glioma-bearing rats treated with anti-EPHA3-modified NPs resulted in significantly higher tumor cell apoptosis (p < .01) than that observed with other formulations and prolonged the median survival time of glioma-bearing rats to 26 days, which was 1.37-fold longer than that of PLGA NPs. The above results indicated that anti-EPHA3-modified NPs may potentially serve as a nose-to-brain drug carrier for the treatment of glioblastoma.     

Targeted delivery of monoclonal antibody conjugated docetaxel loaded PLGA nanoparticles into EGFR overexpressed lung tumour cells

The aim of this study was to develop anti-EGFR antibody conjugated poly(lactide-co-glycolide) nanoparticles (NPs) to target epidermal growth factor receptor, highly expressed on non-small cell lung cancer cells to improve cytotoxicity and site specificity. Cetuximab was conjugated to docetaxel (DTX) loaded PLGA NPs by known EDC/NHS chemistry and characterised for size, zeta potential, conjugation efficiency and the results were 128.4?±?3.6?nm, –31.0?±?0.8?mV, and 39.77?±?3.4%, respectively. In vitro release study demonstrated sustained release of drug from NPs with 25% release at pH 5.5 after 48?h. In vitro cytotoxicity studies demonstrated higher anti-proliferative activity of NPs than unconjugated NPs. Cell cycle analysis and apoptosis study were performed to evaluate extent of cell arrest at different phases and apoptotic potential for the formulations, respectively. In vivo efficacy study showed significant reduction in tumour growth and so antibody conjugated NPs present a promising active targeting carrier for tumour selective therapeutic treatment.     

PNIPAM nanoparticles for targeted and enhanced nose-to-brain delivery of curcuminoids: UPLC/ESI-Q-ToF-MS/MS-based pharmacokinetics and pharmacodynamic evaluation in cerebral ischemia model

Stroke is a one of the leading causes of disease and deaths worldwide, which causes irreversible deterioration of the central nervous system. Curcuminoids are reported to have a potential role in the amelioration of cerebral ischemia but they exhibit low serum and tissue levels due to low solubility and poor absorption. Curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)-loaded PNIPAM nanoparticles (NPs) were prepared by free radical polymerization and characterized for particles size, entrapment efficiency, zeta potential, in vitro release and ex vivo permeation study. Optimized CUR, DMC and BDMC-loaded NPs had the mean size of 92.46?±?2.8, 91.23?±?4.2 and 94.28?±?1.91?nm; zeta potential of ?16.2?±?1.42, ?15.6?±?1.33 and ?16.6?±?1.21 mV; loading capacity of 39.31?±?3.7, 38.91?±?3.6 and 40.61?±?3.6% and entrapment efficiency of 84.63?±?4.2, 84.71?±?3.99 and 85.73?±?4.31%, respectively. Ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectroscopy based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency and brain drug-targeting potential studies post-intranasal (i.n.) administration which showed enhanced bioavailability of curcuminoids in brain as compared to intravenous administration. Improved neurobehavioural activity (locomotor and grip strength) and reduced cytokines levels (TNF-α and IL-1β) was observed in middle cerebral artery occlusion induced cerebral ischemic rats after i.n. administration of curcuminoids NPs. Finally, the toxicity study was performed which revealed safe nature of developed NPs.     

Formulation development of albumin based theragnostic nanoparticles as a potential delivery system for tumor targeting

Background: Generally, chemotherapeutic drugs attack on both normal and tumor cells non-specifically causing life threatening side effects, necessitating targeted drug delivery to tumors.

Purpose: The purpose of this study is to formulate albumin-based nanoparticles for tumor targeted drug delivery and noninvasive diagnosis.

Methods: Albumin based nanoparticles (NPs) were developed as a potential tumor theragnostic agent by entrapping an anti cancer drug, doxorubicin and a near infrared dye, indocyanine green. Theragnostic nanoparticles were prepared using a well established coacervation/nanoprecipitation method followed by lyophilization. The formulation was optimized by varying process parameters using full factorial design of experiments. Release of dye and drug from NPs and physical state of the drug in NPs was studied using DSC. The NPs were injected into tumor bearing mice intravenously and imaged using a bio-imager.

Results: The optimized nanoparticle formulation had a particle size of 125.0?±?1.8?nm, poly dispersity index of 0.180?±?0.057 and zeta potential of ?32.7?±?0.9 mV. The release of dye and drug from the nanoparticles was determined to be quasi-fickian diffusion mediated. Differential scanning calorimetry (DSC) studies revealed the stability of drug in the NP. The in-vivo studies showed enhanced accumulation of the dye loaded NPs at the tumor site than the dye solution, thus allowing noninvasive tumor monitoring.

Conclusion: These results project the newly proposed and evaluated nanoparticle formulation as a potential tumor targeting and imaging delivery system.     

In vitro toxicological assessment of iron oxide,aluminium oxide and copper nanoparticles in prokaryotic and eukaryotic cell types

Metallic nanoparticles (NPs) have a variety of applications in different industries including pharmaceutical industry where these NPs are used mainly for image analysis and drug delivery. The increasing interest in nanotechnology is largely associated with undefined risks to the human health and to the environment. Therefore, in the present study cytotoxic and genotoxic effects of iron oxide, aluminium oxide and copper nanoparticles were evaluated using most commonly used assays i.e. Ames assay, in vitro cytotoxicity assay, micronucleus assay and comet assay. Cytotoxicity to bacterial cells was assessed in terms of colony forming units by using Escherichia coli (gram negative) and Bacillus subtilis (gram positive). Ames assay was carried out using two bacterial strains of Salmonella typhimurium TA98 and TA100. Genotoxicity of these NPs was evaluated following exposure to monkey kidney cell line, CHS-20. No cytotoxic and genotoxic effects were observed for iron oxide, and aluminium oxide NPs. Copper NPs were found mutagenic in TA98 and in TA100 and also found cytotoxic in dose dependent manner. Copper NPs induced significant (p?相似文献   

Concanavaline A conjugated bacterial polyester-based PHBHHx nanoparticles loaded with curcumin for breast cancer therapy

The aim of this study was to evaluate therapeutic potential of curcumin-loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin-loaded NPs (ConA-CUR-NPs) for breast cancer treatment. The size and zeta potential of prepared NPs were about 228?±?5?nm and ?23.3?mV, respectively. The entrapment efficiencies of polymer/drug weight ratios, 1.25CUR-NPs, 2.5CUR-NPs, 5CUR-NPs, ConA-1.25CUR-NPs, ConA-2.5CUR-NPs and ConA-5CUR-NPs were found to be ≈68, 55, 45, 70, 60 and 51%, respectively. Optimized NPs formulations in the freeze-dried form were assessed with their short-term stability for 30 days of storage at 4?°C and 25?°C. Anticancer activity of ConA-CUR-NPs was proved by MTT assay and reconfirmed by double staining and flow cytometry results. The anticancer activity of ConA-CUR-NPs was measured in human breast cancer cells (MDA-MB 231) in vitro, and the results revealed that the ConA-CUR-NPs had better tumor cells decline activity.     

Bioavailability enhancement,Caco-2 cells uptake and intestinal transport of orally administered lopinavir-loaded PLGA nanoparticles

Nanoparticles (NPs) can be absorbed via M cells of Peyer’s patches after oral delivery leading to passive lymphatic targeting followed by systemic drug delivery. Hence, the study was aimed to formulate PLGA NPs of lopinavir. The NPs were prepared by nanoprecipitation, optimized by 3³ factorial design and characterized by TEM, DSC, FTIR studies and safety was assessed by MTT assay. In vivo pharmacokinetic studies were performed in rats. The NPs were discrete spherical structures having particle size of 142.1?±?2.13?nm and entrapment of 93.03?±?1.27%. There was absence of drug-polymer interaction. Confocal images revealed the penetration and absorption of coumarin-loaded NPs in Caco-2 cells and intestine after oral delivery. There was 3.04 folds permeability and 13.9 folds bioavailability enhancement from NPs. The NPs can be promising delivery system for antiretroviral drug by delivering the drug to lymph (major HIV reservoir site) via direct absorption through intestine before reaching systemic circulation.     

Immunoadjuvant potential of cross-linked dextran microspheres mixed with chitosan nanospheres encapsulated with tetanus toxoid

Context: Nasal mucosa is a desirable route for mucosal vaccine delivery. Mucosal co-administration of chitosan nanoparticles with absorption enhancers such as cross-linked dextran microspheres (CDM, Sephadex^®) is a promising antigen delivery system.

Objective: In the current study, the chitosan nanospheres loaded with tetanus toxoid (CHT:TT NPs) was prepared and characterized. The immune responses against tetanus toxoid after nasal administration of CHT:TT NPs alone or mixed with CDM were also determined.

Materials and methods: Chitosan nanospheres were prepared by ionic gelation method. Particle size, releasing profile and antigen stability were evaluated by dynamic light scattering, diffusion chamber and SDS-PAGE methods, respectively. Rabbits were nasally immunized with different formulations loaded with 40 Lf TT. After three times immunizations with 2 weeks intervals, sera IgG titres and nasal lavage sIgA titres were determined.

Results: Mean size of CHT NPs and CHT:TT NPs were 205?±?42?nm and 432?±?85?nm, respectively. The release profile showed that 42.4?±?10.5% of TT was released after 30?min and reached to a steady state after 1.5?h. Stability of encapsulated TT in nanospheres was confirmed by SDS-PAGE. The antibody titres showed that CHT:TT NPs-induced antibody titres were higher than TT solution. CHT NPs mixed with CDM induced the systemic IgG and nasal lavage sIgA titres higher than intranasal administration of TT solution (p?Discussion and conclusion: As the results indicated, these CHT:TT NPs when co-administered with CDM were able to induce more immune responses and have the potential to be used in mucosal immunization.     

Cadmium sulfide nanoparticles trigger DNA alterations and modify the bioturbation activity of tubificidae worms exposed through the sediment

To address the impact of cadmium sulfide nanoparticles (CdS NPs) in freshwater ecosystems, aquatic oligochaete Tubifex tubifex were exposed through the sediment to a low dose (0.52?mg of 8?nm in size of CdS NPs/kg) for 20 days using microcosms. Cadmium (Cd) was released from the CdS NPs-contaminated sediment to the water column, and during this period the average concentrations of Cd in the filtered water fraction were 0.026?±?0.006?µg/L in presence of oligochaetes. Similar experiments with microparticular CdS and cadmium chloride (CdCl₂) were simultaneously performed for comparative purposes. CdS NPs exposure triggered various effects on Tubifex worms compared to control, microsized and ionic reference, including modification of genome composition as assessed using RAPD-PCR genotoxicity tests. Bioaccumulation levels showed that CdS NPs were less bioavailable than CdCl₂ to oligochaetes and reached 0.08?±?0.01?µg Cd/g for CdS NPs exposure versus 0.76?±?0.3?µg Cd/g for CdCl₂ exposure (fresh weight). CdS NPs altered worm’s behavior by decreasing significantly the bioturbation activity as assessed after the exposure period using conservative fluorescent particulate tracers. This study demonstrated the high potential harm of the CdS nanoparticular form despite its lower bioavailability for Tubifex worms.     

Induction of an in vitro reversible hypometabolism through chitosan-based nanoparticles

Objective: Chitosan-based nanoparticles (NPs) were prepared to promote intracellular sustained delivery of the synthetic delta opioid D-Ala(2)-D-Leu(5)-enkephalin (DADLE), prolonging peptide activity and inducing a safe and reversible hypometabolic state.

Materials and methods: NPs were prepared by combining ionotropic gelation and ultrasonication treatment. NP uptake studies and the effects of encapsulated DADLE on HeLa cells proliferation were tested by transmission electron microscopy (TEM) analysis, by immuno-fluorescence and immuno-cytochemistry.

Results: DADLE-loaded NPs are produced with suitable characteristics, a satisfactory process yield (55.4%?±?2.4%) and encapsulation efficiency (64.6%?±?2.1%). NPs are effective in inducing a hypometabolic stasis at a 10^?4?M DADLE concentration. Moreover, as seen from the immunofluorescence study, the effect persists through the recovery period (72?h). Indeed, NPs labelled by anti-enkephalin antibody inside cell nucleus reassert that the in vivo release of the peptide can be prolonged with respect to the case of free peptide supply.

Conclusion: The nanoparticulate drug delivery system described seems to be effective in inducing and prolonging a sort of hibernation-like state in the cells.     

Primary in vitro and in vivo evaluation of norcantharidin-chitosan/poly (vinyl alcohol) for cancer treatment

Abstract

Two novel polymer–drug conjugates norcantharidin-poly(vinyl alcohol) and norcantharidin-chitosan (NCTD-PVA and NCTD-CS) were synthesized via alcoholysis reaction and characterized by ¹H-NMR and FTIR. NCTD was released from the conjugates via hydrolysis, faster in PBS (pH 5.0) than that in PBS (pH 7.4). NCTD-PVA and NCTD-CS inhibited human esophageal carcinoma ECA-109 cell and murine breast cancer EMT6 cell growth in a dose-dependent manner. The IC₅₀ values of NCTD, NCTD-PVA and NCTD-CS on ECA-109 cell at 48?h were 9.4?±?0.9, 55.3?±?3.0 and 168.8?±?8.9?μg/ml, respectively, and the IC₅₀ values of the three compounds on EMT6 cell were 3.1?±?0.3, 30.5?±?5.4 and 90.7?±?8.1?μg/ml, respectively. The two conjugates both induced esophageal carcinoma ECA-109 cell apoptosis and arrested cell cycle at the S phase. Caspase-8 and caspase-3 were activated in the ECA-109 cell after incubating with NCTD-PVA or NCTD-CS. The primary in vivo antitumor activity was assessed in the EMT6 tumor-bearing mouse model. NCTD-PVA and NCTD-CS displayed higher tumor inhibition rates than that of free NCTD.     

Encapsulation of low lipophilic and slightly water-soluble dihydroartemisinin in PLGA nanoparticles with phospholipid to enhance encapsulation efficiency and in vitro bioactivity

Context: PLGA nanoparticles have been widely utilised to encapsulate lipophilic drugs for sustained release.

Objective: This study was to enhance encapsulation efficiency and drug loading for the poorly lipophilic drug dihydroartemisinin (DHA) in PLGA nanoparticles, where amphiphilic phospholipid was employed as the intermediate. Materials and methods: DHA-phospholipid complex formulation was optimised using the response surface method. DHA-phospholipid complex-nanoparticles (DHA-PLC-NPs) were prepared using the solvent evaporation method. Results: The particle size, zeta potential, entrapment efficiency and drug loading of the nanoparticles were 265.3?±?7.9?nm, ?21.4?±?6.3?mV, 74.2?±?6.5% and 2.80?±?0.35%, respectively. Compared with the rapidly released free form, DHA underwent sustained release from the nanoparticles. DHA-PLC-NPs presented stronger cell proliferative inhibition than DHA treatment alone and apoptosis was obviously induced after DHA-PLC-NPs treatment. Conclusion: Phospholipid complexes are useful intermediate to improve the lipophilicity of drugs, the interaction with the hydrophobic core of PLGA and the encapsulation efficiency of poorly lipophilic drugs in polymeric nanoparticles.     

Designing siRNA-conjugated plant oil-based nanoparticles for gene silencing and cancer therapy

Abstract

In this study, the anticancer activities of two siRNA carriers were compared using a human lung adenocarcinoma epithelial cell line (A549). Firstly, poly(styrene)-graft-poly(linoleic acid) (PS-g-PLina) and poly(styrene)-graft-poly(linoleic acid)-graft-poly(ethylene glycol) (PS-g-PLina-g-PEG) graft copolymers were synthesized by free-radical polymerization. PS-PLina and PS-PLina-PEG nanoparticles (NPs) were prepared by solvent evaporation method and were then characterized. The size was found as 150?±?10?nm for PS-PLina and 184?±?6?nm for PS-PLina-PEG NPs. The NPs were functionalized with poly(l-lysine) (PLL) for c-myc siRNA conjugation. siRNA entrapment efficiencies were found in the range of 4–63% for PS-PLina-PLL and 6–42% for PS-PLina-PEG-PLL NPs. The short-term stability test was realised for 1?month. siRNA release profiles were also investigated. In vitro anticancer activity of siRNA-NPs was determined by MTT, flow cytometry, and fluorescence microscopy analyses. Obtained findings showed that both NPs systems were promising as siRNA delivery tool for lung cancer therapy.     

Influence of mefenamic acid on the intestinal absorption and metabolism of three bioactive flavones in Radix Scutellariae and potential pharmacological impact

Context: Mefenamic acid (MEF) and the dried root of Scutellaria baicalensis Georgi (Radix Scutellariae, RS) share a high possibility of combined medication to treat inflammation.

Objective: The present study investigates the impact of MEF on absorption/disposition of three major components in RS (baicalein, B; wogonin, W; oroxylin A, OA) and further pharmacological changes.

Materials and methods: The apparent permeability (P_app) and percentage of metabolism of B, W and OA at 10?μΜ were measured at the absence/presence of MEF (100?μΜ) in the Caco-2 cell monolayer model. A modified whole blood assay was employed to quantify prostaglandin E₂ (PGE₂) 4, 6 and 8?h post-oral administration with water suspension of MEF at 40?mg/kg and RS at 200?mg/kg.

Results: In the presence of MEF, P_app of B, W and OA were increased from 1.69?±?0.89?×?10^?6, 1.57?±?0.10?×?10^?6 and 3.09?±?0.70?×?10^?6?cm/sec to 5.24?±?0.27?×?10^?6, 6.08?±?0.19?×?10^?6 and 4.13?±?0.38?×?10^?6, whereas their percentage of metabolism was decreased from 72.75?±?2.44%, 73.27?±?3.25% and 89.84?±?2.99% to 21.11?±?0.69%, 17.90?±?5.55% and 45.44?±?3.38%. PGE₂ level was much lower in the co-administration group (49.04?±?2.03?pg/ml) than in the MEF group (73.13?±?3.03?pg/ml) or RS group (494.37?±?11.75?pg/ml) 4?h post MEF dosing, suggesting a synergic effect.

Discussion and conclusion: Co-administration of MEF and RS could induce potential alterations in their pharmacokinetic profiles and anti-inflammatory effects.     

Nonselective uptake of silver and gold nanoparticles by wheat

Abstract

Metallic nanoparticles (NPs) show unique reactivity to crop plants, but the uptake mechanisms remain unclear. We quantitatively evaluated the phytoavailability of particles to wheat (Triticum aestivum L.) in hydroponics upon exposure to AgNPs (15?nm) or AuNPs (13 and 33?nm). Particles were physically separated from the released Ag ions by a dialysis membrane, under which particle-specific uptake of AgNPs could be discerned. Plants did not differentiate AgNPs and AuNPs during particle uptake, with uptake rate constants of 1.1?±?0.1, 1.2?±?0.3, and 1.2?±?0.1?L?kg^?1?h^?1 for AgNPs, AuNPs (13?nm), and AuNPs (33?nm), respectively. We found little effect of particle size (13 or 33?nm AuNPs) or core composition (Ag or Au) on particle bioavailability. Plants stimulated the subsequent uptake of Evans blue stain and showed cell damage in root tips. These results imply similar physiological processes involved in particle-specific uptake of AgNPs and AuNPs. The internalization of particles was further confirmed by single particle inductively coupled plasma mass spectrometry (spICP-MS) and transmission electron microscope-energy dispersive spectrometer (TEM-EDS) analysis. The work here builds the knowledge base for the nature of particle-specific uptake of different NP types by crop plants.