Preparation,optimization by 2<Superscript>3</Superscript> factorial design,characterization and in vitro release kinetics of lorazepam loaded PLGA nanoparticles

The aim of this work was to formulate the lorazepam loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles by optimization of different preparation variables using 2³ factorial design. The effect of three independent factors, the amount of polymer, concentration of the stabilizer and volume of organic solvent was investigated on two dependent responses, i.e., particle size and % drug entrapment efficiency. By using PLGA as polymer, PVA as a stabilizer and dimethyl sulfoxide as organic solvent lorazepam loaded PLGA nanoparticles were successfully developed through modified nanoprecipitation method. FTIR and DSC studies were carried out to examine the interaction between the excipients used and to explore the nature of the drug, the formulation and the nature of drug in the formulations. These nanoparticles were characterized for particle size, shape, zeta potential, % drug entrapment efficiency, % process yield and in vitro drug release behavior. In vitro evaluation showed particles size between 161.0 ± 5.4 and 231.9 ± 4.9 nm, % drug entrapment efficiency of formulations was in the range of 60.43 ± 5.8 to 75.40 ± 1.5, % process yield at 68.34 ± 2.3 to 81.55 ± 1.3 was achieved and in vitro drug release for these formulations was in the range of 49.2 to 54.6%. Different kinetics models, such as zero order, first order, Higuchi model, Hixson-Crowell model and Korsmeyer- Peppas model were used to analyze the in vitro drug release data. Preferred formulation showed particle size of 161.0 ± 5.4 nm, PDI as 0.367 ± 0.014,–25.2 mV zeta potential, drug entrapment efficiency as 64.58 ± 3.6% and 72.48 ± 2.5% process yield. TEM results showed that these nanoparticles were spherical in shape, and follow the Korsmeyer-Peppas model with a release exponent value of n = 0.658.     

Lomustine loaded chitosan nanoparticles: characterization and in-vitro cytotoxicity on human lung cancer cell line L132

The aim of this work was to prepare chitosan nanoparticles loaded with antineoplastic drug Lomustine (LCNPs), by ionic-gelation method with homogenization. The nanoparticles were characterized for particle size, polydispersity index (PDI), surface morphology, encapsulation efficiency, in-vitro drug release and cytotoxicity on human lung cancer cell line L132 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The particle size, zeta potential and encapsulation efficiency of prepared nanoparticles ranged from 75 ± 1.1 to 637 ± 1.6 nm (PDI from 0.05 ± 0.001 to 0.18 ± 0.007), 37.2 ± 0.21 to 53.8 ± 0.18 mV and 66.74 ± 1.4 to 98.0 ± 1.8% respectively. The particles were spherical in shape with smooth surface in scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images. Mechanical shearing by homogenization treatment significantly changed the nanoparticle size. The drug release rate was biphasic and diffusion controlled over the 8 h. LCNPs greatly inhibited the growth of the L132 cancer cell line used in this study in comparison to the native Lomustine (LMT).     

Au nanoparticle decorated silicate network for the amperometric sensing of isoniazid

Au nanoparticle (nAu) based electrochemical platform for the amperometric sensing of isoniazid at sub-nanomolar level is developed. The sol-gel derived 3-dimensional silicate network pre-assembled on a conducting substrate is chemically decorated with nAu of 70-100 nm by seed-mediated growth approach. The Au nanoseeds are first chemisorbed onto the thiol functional groups of the silicate network and their size was enlarged by hydroxylamine seeding. The nanoparticles efficiently catalyze the oxidation of isoniazid at less positive potential. Large decrease in the overpotential and significant enhancement in the anodic peak current with respect to the polycrystalline Au electrode are observed. The nanoparticle based platform is highly sensitive (4.03 ± 0.01 nA/nM) and it linearly responds to isoniazid up to the concentration of 1 mM. It could detect as low as 0.1 nM (S/N = 5) of isoniazid at the potential of 10 mV in aqueous solution without any redox mediator. The catalytic response of the sensing platform depends on the amount of nanoparticles loaded onto the silicate network. Very interestingly, the sensing platform could simultaneously detect isoniazid and hydrazine in their coexistence without compromising the sensitivity. Well separated individual voltammetric response is obtained for both analytes. The sensing platform is highly stable and it can be repeatedly used for 7 days.     

Effect of polyethylene glycol on preparation of rifampicin-loaded PLGA microspheres with membrane emulsification technique

Monodisperse poly(lactide-co-glycolide) (PLGA) microspheres containing rifampicin (RFP), anti-tubercle drug, as hydrophobic model drug were prepared by solvent evaporation method with a membrane emulsification technique using Shirasu Porous Glass (SPG) membranes. Five kinds of rifampicin-loaded PLGA (RFP/PLGA) microspheres with different sizes were prepared by changing pore size of the membranes. Effect of polyethylene glycol (PEG) added to polyvinyl alcohol (PVA) solution (continuous phase) upon the monodispersity of microspheres was studied. PEG was used as a stabilizer for microspheres dispersing in PVA solution. The most suitable molecular weight of PEG as a stabilizer was 20,000. RFP/PLGA microspheres prepared with PEG20000 were apparently more uniform than those prepared without PEG. The yield of RFP/PLGA microspheres was 100%. The initial burst observed in the release of RFP from RFP/PLGA microspheres was suppressed by the addition of PEG.     

A new kind of polyion complex nanoparticles and the covalent drug-loading pattern for doxorubicin and pH-controlled release

The one-pot synthesis method was developed for the preparation of complex nanoparticles with a narrow size distribution and stable morphology. The vinyl monomers of (2-dimethylamino)ethyl methacrylate (DEMA) and diacetone acrylamide (DAA) were copolymerized in the presence of alginic acid in an aqueous solution without any organic solvents or surfactants, yielding stable complex nanoparticles in one-pot synthesis. The nanoparticle was composed of the complex of poly(DEMA-co-DAA) and alginic acid. The complex was formed via electrostatic interaction between polycations of DEMA and polyanions of alginate. The residual alginate segment around the core formed the shell of the nanoparticles. The average diameter of the nanoparticles varied from 120 to 213 nm when the molar percentage of DAA changed from 0.5 to 0 with respect to DEMA. The anti-cancer drug doxorubicin could be loaded onto the nanoparticles with a high-loading efficiency through the formation of polymer–drug conjugate. The drug release could be controlled by adjusting the pH value of the medium.     

Mechanistic study of hydrolytic erosion and drug release behaviour of PLGA nanoparticles: Influence of chitosan

The hydrolytic erosion of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (PLGA-NPs) was investigated in vitro. The changes in physical properties of the nanoparticles with time were evaluated by ultra high-pressure liquid chromatographic (UHPLC) analysis, particle size analysis and scanning electron microscopy (SEM). Mass reduction data demonstrated a triphasic erosion pattern for PLGA-NPs with nearly no mass loss (3.0%) up to a week, followed by a rapid mass loss (weeks 1-3, 61.4%), and further followed by slow mass loss (weeks 3-5, 19.8%). SEM revealed microcavitation on the surface of nanoparticles, which tended to increase with the erosion time and eventually particle fragmentation was evident at 5 weeks. A significant increase in particle size was observed at 4 weeks which can be attributed to particle aggregation, however, at about 5 weeks, the particle size decreased significantly owing to particle fragmentation. The hydrolytic erosion of PLGA-NPs was found to be specifically proton catalyzed. The release profile of the model drug, moxifloxacin, from PLGA-NPs was closely related to nanoparticle erosion except for the initial burst release which was based on diffusion. The presence of chitosan in the PLGA-NPs accelerated the rate of erosion of the nanoparticles and reduced the burst release of the drug. An understanding of the erosion mechanism and alteration in erosion by chitosan could give desirable and more uniform drug release kinetics from PLGA-NPs.     

Synthesis of alginate stabilized gold nanoparticles by γ-irradiation with controllable size using different Au3+ concentration and seed particles enlargement

Gold nanoparticles with pre-selected size in the range 5–40 nm were synthesized by γ-irradiation of Au³⁺ solution containing natural polysaccharide alginate as a stabilizer. The gold nanoparticles with controllable size were prepared by two approaches: (i) varying the concentration of Au³⁺ from 0.25 to 1 mM and alginate from 0.25% to 1% (w/v) and (ii) enlargement of seed particles with double size from 20 to 40 nm at [Au³⁺]/[Au⁰]=6. The obtained gold nanoparticles were characterized by UV–vis spectroscopy and transmission electron microscopy. The results indicated that γ-irradiation method is suitable for production of gold nanoparticles with controllable size and high purity.     

Tailoring the carbon nanostructures grown on the surface of Ni-Al bimetallic nanoparticles in the gas phase

A gas-phase, one-step method for producing various aerosol carbon nanostructures is described. The carbon nanostructures can be selectively tailored with either straight, coiled, or sea urchin-like structures by controlling the size of Ni-Al bimetallic nanoparticles and the reaction temperature. The carbon nanostructures were grown using both conventional spray pyrolysis and thermal chemical vapor deposition. Bimetallic nanoparticles with catalytic Ni (guest) and non-catalytic Al (host) matrix were reacted with acetylene and hydrogen gases. At the processing temperature range of 650-800 °C, high concentration straight carbon nanotubes (S-CNTs) with a small amount of coiled carbon nanotubes (C-CNTs) can be grown on the surface of seeded bimetallic nanoparticle size <100 nm, resulting from consumption of the melting Al matrix sites; sea urchin-like carbon nanotubes (SU-CNTs) of small diameter (～10±4 nm) can be grown on the bimetallic nanoparticle size >100 nm, resulting from the significant size reduction of the available Ni sites due to thermal expansion of molten Al matrix sites without consumption of Al matrix. However, at the processing temperature range of 500-650 °C, C-CNTs can be grown on the bimetallic nanoparticle size <100 nm due to the presence of Al matrix in the bimetallic nanoparticles; SU-CNTs of large diameter (～60±13 nm) can also be grown on the bimetallic nanoparticle size >100 nm due to the isolation of Ni sites in the Al matrix.     

Preparation, characterization of hydrophilic and hydrophobic drug in combine loaded chitosan/cyclodextrin nanoparticles and in vitro release study

The compound nanoparticles of chitosan (CS) and cyclodextrin (CD) loading with hydrophilic and hydrophobic drug simultaneously were prepared via the cross-linking method. Methotrexate (MTX) and calcium folinate (CaF) were selected as the model drugs. The prepared nanoparticles were characterized by FT-IR spectroscopy to confirm the cross-linking reaction between CS and cross-linking agent. X-ray diffraction (XRD) was performed to reveal the form of the drug after encapsulation. The average size of nanoparticles ranged from 308.4 ± 15.22 to 369.3 ± 30.01 nm. The nanoparticles formed were spherical in shape with high zeta potentials (higher than +30mV). In vitro release studies in phosphate buffer saline (pH 7.4) showed an initial burst effect and followed by a slow drug release. Cumulative release data were fitted to an empirical equation to compute diffusional exponent (n), which indicated the non-Fickian trend for drug release.     

pH-dependent release from ethylcellulose microparticles containing alginate and calcium carbonate

Ethylcellulose microparticles containing alginate and calcium carbonate nanoparticles were prepared by spray drying water-in-oil emulsion. Alginate solution (3%) in distilled water was used as an aqueous phase, ethylcellulose solution (5%) in dichloromethane as an oil phase, and sorbitan sesquioleate as an emulsifier. The nanoparticles of calcium carbonate were dispersed into the emulsion. By spray-drying the emulsion, ethylcellulose microparticles containing alginate and calcium carbonate were obtained. When the ratios of alginate to calcium carbonate were 4:1 and 2:1, the pH dependency of the release was marked and the degree of release was suppressed in acidic conditions. When the ratio increased to 1:2, the degree of release increased while the pH-dependent release profiles were maintained. Cavities created by the dissolution of calcium carbonate could account for the increased release.     

功能化PbS量子点的水相合成及结构表征

在水溶液中以Pb(NO3)2和Na2S为原料,巯基乙酸为稳定剂,合成了水溶性PbS量子点.用透射电子显微镜、扫描电子显微镜、粒度分析仪和红外光谱对PbS量子点进行了表征,结果表明所合成的PbS量子点的平均粒径为25 nm左右,分散性好,且巯基乙酸成功修饰于PbS纳米粒子表面,使其具有进一步与生物分子偶联的作用.     

Poly(lactic-co-glycolic acid) as a particulate emulsifier

The structure and stability of emulsions formed in the presence of nanoparticles of poly(lactic-co-glycolic acid) (PLGA) were characterised. From oil-water contact angles on PLGA films, it was deduced that particle surface hydrophobicity is linked to the oil phase polarity. Incorporation of polyvinyl alcohol molecules into the nanoparticle surfaces reduces the particle hydrophobicity sufficiently for oil-in-water emulsions to be preferentially stabilised. PLGA nanoparticles enhance the stability of emulsions formed from a wide range of oils of different polarities. The nanoparticle concentration was found to be a key parameter controlling the average size and coalescence stability of the emulsion drops. Visualisation of the interfacial structure by electron microscopy indicated that PLGA nanoparticles were located at the drop surfaces, evidence of the capacity of these particles to stabilise Pickering-type emulsions. These results provide insights into the mechanism of PLGA nanoparticle stabilisation of emulsions.     

Ag/Au纳米粒子的没食子酸还原制备及其共振瑞利散射光谱测定人血清总蛋白

以没食子酸为还原剂和稳定剂,用种子生长法制备出粒径均匀、单分散性和稳定性好、近球形的Ag/Au 核壳纳米粒子.高分辨透射电镜(HRTEM)与 X-射线能量色散光谱仪(EDX)测试表明,在Ag/Au摩尔比为1:1.6时,Au已完全包裹在Ag纳米粒子表面时,平均粒径为25 nm.以此摩尔比制备的Ag/Au核壳纳米粒子为探针...     

Development of a polymer system for the delivery of daunorubicin to tumor cells to overcome drug resistance

Method for the synthesis of polymeric nanoparticles (NP) with encapsulated daunorubicin (DNR) was developed on the basis of double emulsion solvent evaporation technique using biodegradable poly(lactide-co-glycolide) (PLGA), which is aimed at customization of pharmacokinetic properties of the preparation, enhanced accumulation of DNR in tumor cells and prolongation of its action. The obtained polymer nanoparticles (DNR-PLGA) had average size ranging around 138±36 nm, with zeta-potential of –25.3 mV and the polydispersity index (PDI) of 0.072. The release kinetics of DNR from polymer nanoparticles at pH 7.4 and 5.0 has been studied. In vitro studies showed similar specific activity of DNR- PLGA in K562 and MCF-7 cancer cell lines together with an increase in activity in K562 Adr and MCF-7 Adr cell lines, which are anthracycline resistant, by 1.6 and 3.4 times. The study demonstrated the efficacy of the developed PLGA-based DNR delivery system in the improvement of antitumor effect of DNR, overcoming multidrug resistance in cancer cells, and also in the decrease in nonspecific toxicity of the preparation.     

Nanoformulation Development to Improve the Biopharmaceutical Properties of Fisetin Using Design of Experiment Approach

This study aimed to design an effective nanoparticle-based carrier for the oral delivery of fisetin (FST) with improved biopharmaceutical properties. FST-loaded nanoparticles were prepared with polyvinyl alcohol (PVA) and poly(lactic-co-glycolic acid) (PLGA) by the interfacial deposition method. A central composite design of two independent variables, the concentration of PVA and the amount of PLGA, was applied for the optimization of the preparative parameter. The responses, including average particle size, polydispersity index, encapsulation efficiency, and zeta potential, were assessed. The optimized formulation possessed a mean particle size of 187.9 nm, the polydispersity index of 0.121, encapsulation efficiency of 79.3%, and zeta potential of −29.2 mV. The morphological observation demonstrated a globular shape for particles. Differential scanning calorimetry and powder X-ray diffraction studies confirmed that the encapsulated FST was presented as the amorphous state. The dissolution test indicated a 3.06-fold increase for the accumulating concentrations, and the everted gut sac test showed a 4.9-fold gain for permeability at the duodenum region. In conclusion, the optimized FST-loaded nanoparticle formulation in this work can be developed as an efficient oral delivery system of FST to improve its biopharmaceutic properties.     

壳聚糖-海藻酸盐纳米粒子的制备及其对BSA的载药与释放特性

带相反电荷的聚电解质在水溶液中能通过静电相互作用自组装形成壳聚糖-海藻酸盐纳米粒。利用动态光散射纳米粒度分析仪考察了钙离子及壳聚糖对粒子粒径的影响。结果表明：钙离子的存在可使粒子粒径从268．5nm降为203．4nm,但随着钙离子含量的继续升高,粒径迅速增大,当钙离子浓度大于0．45g／L时形成凝胶。壳聚糖含量的增加和蛋白的包裹均会使粒径增大。所制备的纳米粒对BSA具有较高的包栽能力,并有一定的缓释作用。当壳聚糖投料量增加时,可使BSA在pH=7．4的PBS中的释放减慢。     

Simple reductant concentration-dependent shape control of polyhedral gold nanoparticles and their plasmonic properties

We report a facile seed-mediated method for the synthesis of monodisperse polyhedral gold nanoparticles, with systematic shape evolution from octahedral to trisoctahedral structures. The control over the particle growth process was achieved simply by changing the concentration of the reductant in the growth solution, in the presence of small spherical seed nanoparticles. By progressively increasing the concentration of the reductant used in the growth solution (ascorbic acid), while keeping the amount and type of added surfactant constant, the morphology of the gold nanoparticles was varied from octahedral to truncated octahedral, cuboctahedral, truncated cubic, cubic, and finally trisoctahedral structures. These nanoparticles were monodisperse in size, possessed similar volumes, and were naturally oriented so that their larger crystal planes were face down on quartz substrates when deposited from the solution. By adjusting the volume of gold seed nanoparticle solution added to a growth solution, the size of the simplest gold nanoparticles (with a highly symmetric cubic morphology) could be tuned from 50 ± 2.1 to 112 ± 11 nm. When other seed nanoparticles were used, the size of the cubic Au nanoparticles reached 169 ± 7.0 nm. The nanoparticle growth mechanism and the plasmonic properties of the resulting polyhedral nanoparticles are discussed in this paper.     

Release of rifampicin from chitosan, PLGA and chitosan-coated PLGA microparticles

Recently three groups of rifampicin (RIF)-loaded microparticles (MPs), consisting of chitosan (CHT), PLGA and PLGA/CHT mixtures, were assessed in terms of RIF-loading and retention during nebulisation. The CHT-coated PLGA MPs were found to exhibit high RIF-loading ability together with nebulisation ability, stability, and mucoadhesive properties. All MP types had comparable toxicity towards alveolar cells which was significantly lower than that of the free drug. Herein, we study the release of RIF from all MP-types, during incubation in buffer with pH values: 4.40 and 7.40. Results show that CHT particles exhibit a higher burst release compared to PLGA MPs; at pH 4.40, which is explained by the higher solubility of CHT in acidic media. At pH 7.40 burst release from CHT MP's is significantly lower when CHT is crosslinked with glutaraldehyde, which is consistent with their - previously observed - increased stability during nebulization. From PLGA MPs, RIF release was pH independent under the conditions applied, while the amount of PVA (stabilizer) considerably affected drug release. When PLGA MP's were coated with CHT, at pH 7.40 the retention of RIF increased further (compared to non-coated MPs), while at pH 4.40 the release was faster from the CHT-coated particles. Concluding, it is proven that when PLGA MPs are coated with CHT, in addition to increased particle mucoadhesive properties, the release kinetics of RIF are modified.     

Physical basis for the formation and stability of silica nanoparticles in basic solutions of monovalent cations

The colloidal stability, phase behavior, and solubility of silica nanoparticles (3-10 nm) that are formed in basic solutions of monovalent cations (primarily tetrapropylammonium) are investigated using a combination of chemical equilibria and electrostatic models. The free-energy gain associated with the formation of an electric double layer surrounding the nanoparticle was obtained by solving the Poisson-Boltzmann equation. This free energy is an important contribution to the total free energy of the particle and is second only to the formation of Si-O-Si bonds. The free energy of formation of the nanoparticles becomes increasingly negative with an increase in particle size and density, which explains the lower solubility of nanoparticles compared to that of amorphous silica. There is a minimum in the free energy of condensation as a function of size that qualitatively explains why the formation of small particles with a uniform size (<5 nm) is energetically favorable. The electrostatic models provide an estimate for the nanoparticle surface potential, which is significantly higher (-120 to -170 mV) than that of zeolite silicalite-1 (-60 to -80 mV) prepared in similar solutions. This result explains the stability of such small particles in solution. It is also shown that a condensation model that is based on silica solubility can describe the phase diagram for nanoparticle formation reported by Fedeyko et al. (J. Phys. Chem. B 2004, 108, 12271) over a wide range of pH and, in conjunction with a complexation model, provides an approximate equilibrium constant (pKa = 8.4) for the dissociation of nanoparticle silanol groups.     

Formulation design, preparation and physicochemical characterizations of solid lipid nanoparticles containing a hydrophobic drug: effects of process variables

This study aimed to prepare solid lipid nanoparticles (SLNs) of a hydrophobic drug, tretinoin, by emulsification-ultrasonication method. Solubility of tretinoin in the solid lipids was examined. Effects of process variables were investigated on particle size, polydispersity index (PI), zeta potential (ZP), drug encapsulation efficiency (EE), and drug loading (L) of the SLNs. Shape and surface morphology of the SLNs were investigated by cryogenic field emission scanning electron microscopy (cryo-FESEM). Complete encapsulation of drug in the nanoparticles was checked by cross-polarized light microscopy and differential scanning calorimetry (DSC). Crystallinity of the formulation was analyzed by DSC and powder X-ray diffraction (PXRD). In addition, drug release and stability studies were also performed. The results indicated that 10mg tretinoin was soluble in 0.45±0.07 g Precirol? ATO5 and 0.36±0.06 g Compritol? 888ATO, respectively. Process variables exhibited significant influence in producing SLNs. SLNs with <120 nm size, <0.2 PI, >I30I mV ZP, >75% EE, and ～0.8% L can be produced following the appropriate formulation conditions. Cryo-FESEM study showed spherical particles with smooth surface. Cross-polarized light microscopy study revealed that drug crystals in the external aqueous phase were absent when the SLNs were prepared at ≤0.05% drug concentration. DSC and PXRD studies indicated complete drug encapsulation within the nanoparticle matrix as amorphous form. The drug release study demonstrated sustained/prolonged drug release from the SLNs. Furthermore, tretinoin-loaded SLNs were stable for 3 months at 4°C. Hence, the developed SLNs can be used as drug carrier for sustained/prolonged drug release and/or to improve oral absorption/bioavailability.