Developing combination of artesunate with paclitaxel loaded into poly-d,l-lactic-co-glycolic acid nanoparticle for systemic delivery to exhibit synergic chemotherapeutic response

Objectives: Paclitaxel (PTX) has been indicated for the treatment of a variety of solid tumors, whereas artesunate (ART) has been reported to have the potential for use in combination chemotherapy. In this study, the combination of ART and PTX was prepared in nanoparticle to induce the synergic effect and improve therapeutic efficiency in treatment of breast cancer.

Methods: Dual anticancer agents (PTX and ART) were loaded into Poly-D,L-lactic-co-glycolic acid (PLGA) nanoparticle (NP) by solvent evaporation technique from oil-in-water emulsion, stabilized with Tween 80. Physicochemical properties of obtained nanoparticles (PTX-ART-NPs) were characterized including particle size (Z), polydispersity index (PDI), zeta potentials (ZP), encapsulation efficiency (EE), and in-vitro drug release. Combination index (CI) was calculated to determine the synergic effect of the combination and select the best ratio of ART and PTX. The final NPs analyzed intracellular uptake, cytotoxicity assay, and apoptosis study.

Results: The final NP had a small size (around 120?nm) with a narrow size distribution (PDI <0.3). EE values for each drug were 87.8?±?1.1% and 99.5?±?0.1% for ART and PTX, respectively, and drugs were released from NPs in a controlled release pattern. All combinations of PTX and ART had CI values under 1, which confirmed the synergic effects. Meanwhile, NP preparation increased cytotoxicity on three breast cancer cell-lines comparable to free drugs.

Conclusions: Combination of ART- and PTX-loaded PLGA NP showed promising results for anticancer therapy, especially for breast cancer treatment.     

Preparation and evaluation of N-caproyl chitosan nanoparticles surface modified with glycyrrhizin for hepatocyte targeting

Background: The development of an efficient targeted drug delivery system into cells is an important subject for the advancement of drug carriers. In this study, a novel hepatocyte-targeted delivery system with glycyrrhizin (GL) surface modification based on N-caproyl chitosan (CCS) has been developed. Method: CCS was synthesized by acylation of amino group of chitosan, and GL was oxidized to be conjugated to the surface of N-caproyl chitosan nanoparticles (CCS-NPs-GL). The synthesized nanoparticles were first characterized for their morphology, particle size, zeta potential, in vitro stability in plasma, tissue distribution, and hepatocyte-targeting uptake in vivo. Results: The obtained results showed that the spherical and discrete nanoparticles prepared with oxidized GL/CCS ratio of 0.14:1 (w/w) exhibited a positive electrical charge and associated adriamycin quite efficiently (association efficiency: 87.5%). The prepared nanoparticles also possessed dimensional and GL surface-binding stability and slow release property in plasma in vitro. The biodistribution of these particles after intravenous injections in mice revealed accumulating drug concentrations in the liver, spleen, and lungs while decreasing drug concentrations in the heart and kidney. The content of adriamycin-loaded CCS-NPs-GL in the liver was 1.6 times higher than that of non-GL-modified CCS-NPs. Furthermore, in vivo uptake of CCS-NPs-GL by rat hepatocytes showed 2.1 times higher nanoparticle uptake compared with non-GL-modified CCS-NPs, which suggested that CCS-NPs-GL were preferentially distributed in hepatocytes by a ligand–receptor interaction. Conclusion: This article indicated that CCS-NPs-GL was a stable and effective drug delivery vehicle for hepatocyte targeting.     

纳米CeO2的反相微乳法制备和表征

通过一种简单的2-乙基己基磺基琥珀酸钠（AOT）-正辛烷-水微乳液体系成功的制得了纳米CeO2．利用激光粒径分布仪、X射线衍射仪（XRD）、差示扫描量热仪（DSC）和傅立叶转换红外光谱仪（FT-IR）表征了所得样品的结构。初步研究了纳米CeO2形成的机理。结果表明，实验所得纳米CeO2的粒径分布均匀；纳米CeO2前驱体表明吸附有表面活性剂AOT，这有利于纳米粒子的分散；经煅烧后的纳米CeO2属于立方晶体结构。     

Morphology and photophysical properties of polymer thin films dispersed with dye nanoparticle

We prepared nanoparticles of an organic dye, acridine orange (AO), dispersed in poly(methacrylic acid) (PMA) films by spin-coating the solution of the two components. The surface of the AO/PMA films became bumpier with increasing AO concentration (c_AO). The absorption and fluorescence spectra of AO/PMA films exhibited a marked dependence on c_AO at low c_AO (c_AO < 2.1 × 10^− 1 mol kg^− 1), and were independent of c_AO at high c_AO (c_AO > 2.1 × 10^− 1 mol kg^− 1). The peak shift of fluorescence spectra with changing c_AO was as large as ∼ 100 nm.     

高致密度FeNi纳米颗粒薄膜制备与性能研究

传统磁控溅射装置制备的纳米颗粒薄膜粒径不均一并且实现粒径大小调控比较困难.本研究采用电场辅助沉积技术,在沉积平台施加5～30 kV的电场,以Si(100)为衬底制备了一系列纳米颗粒粒径均一的高致密度FeNi纳米颗粒薄膜材料.通过XRD、SEM以及VSM测量,研究了不同沉积电场下FeNi纳米颗粒薄膜的结构、形貌和磁性能....     

Glucose-conjugated chitosan nanoparticles for targeted drug delivery and their specific interaction with tumor cells

A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles （GCNPs）, was developed for specific recognition and interaction with glucose transporters （Gluts） over-expressed by tumor cells. GC was synthesized by using succinic acid as a linker between glucosamine and chitosan （CS）, and successful synthesis was confirmed by NMR and elemental analysis. GCNPs were prepared by ionic crosslinking method, and characterized in terms of morphology, size, and zeta potential. The optimally prepared nanoparticles showed spherical shapes with an average particle size of （187.9 ± 3.8） nm and a zeta potential of （-15.43 ± 0.31） mV. The GCNPs showed negligible cytotoxicity to mouse embryo fibroblast and 4T1 cells. Doxorubicin （DOX） could be efficiently entrapped into GCNPs, with a loading capacity and encapsulation efficiency of 20.11% and 64.81%, respectively. DOX-Ioaded nanoparticles exhibited sustained-release behavior in phosphate buffered saline （pH 7.4）. In vitro cellular uptake studies showed that the GCNPs had better endocytosis ability than CSNPs, and the antitumor activity of DOX/GCNPs was 4-5 times effectiveness in 4T1 cell killing than that of DOX/CSNPs. All the results demonstrate that nanoparticles decorated with glucose have specific interactions with cancer cells via the recognition between glucose and Gluts. Therefore, Gluts-targeted GCNPs may be promising delivery agents in cancer therapies.     

Preparation and characterisation of silver nanoparticle coated on cellulose paper: evaluation of their potential as antibacterial water filter

This study investigates the ability of cellulose filter paper coated with silver nanoparticles to remove Escherichia coli from drinking water. The cellulose filter paper was coated with silver nanoparticles by a chemical reduction method using two different ratios of sodium borohydride and silver nitrate. In consideration of drinking-water quality standards and non-carcinogenic health risks, the optimum sodium borohydride:silver nitrate ratio for coating the cellulose filter paper was determined by comparing the silver in the effluent after E. coli removal. For both ratios, 100% E. coli removal was realised. In terms of the silver in the effluent, only the first two lowest concentrations for both ratios of sodium borohydride and silver nitrate were compliant with the drinking-water quality standards, demonstrating hazard quotients (HQs) between 0.084 and 0.484. On the basis of the highest level of E. coli removal with the lowest HQ value, the optimum sodium borohydride:silver nitrate ratio for coating the cellulose filter paper as an antibacterial water filter was 2:1 molar ratio (0.002 M:0.001 M). Silver nanoparticle-coated cellulose filter paper was found to be an inexpensive and easy-to-use emergency antibacterial water filter to generate clean drinking water.     

Preparation of a novel liver-targeting nanoparticle of norcantharidin derivative and evaluation of its anti-tumour activity

In our study, a novel hepatocyte-targeting norcantharidin (NCTD) derivative lactosyl-norcantharidin (Lac-NCTD) was synthesised using ethanediamine as a truss arm, and lactosyl-norcantharidin nanoparticles (Lac-NCTD-NPs) were obtained by an ionic cross-linkage process with an entrapment efficiency of (80.29?±?0.56)%. The release of Lac-NCTD-NPs in vitro was then investigated by means of a dialysis method, and its sustained effect was evident. The in vitro anti-tumour activities of Lac-NCTD and Lac-NCTD-NPs were studied by their cytotoxic effects on HepG2, SMMC-7721 and SGC-7901 cells. The results showed that the IC₅₀ values of Lac-NCTD and Lac-NCTD-NPs cytotoxicity against HepG2 and SMMC-7721 cells were lower compared to NCTD, and the anti-tumour effects could be remarkably inhibited by galactosylated fetal bovine serum (Gal-FBS) as a competitor of the asialoglycoprotein receptor. The cytotoxic effects against SGC-7901 cells were relatively high, even higher than NCTD, and Gal-FBS had no influence on them at all. The amount of Lac-NCTD accumulated in SMMC-7721 cells was assayed by high-performance liquid chromatography, which indicated that Lac-NCTD may be able to permeate the cell membrane in its unchanged form. The anti-tumour activities of Lac-NCTD and Lac-NCTD-NPs in vivo were evaluated in mice bearing an H22 tumour. The results suggested that tumour growth was effectively inhibited by all treatments, including NCTD, Lac-NCTD and Lac-NCTD-NPs, with Lac-NCTD-NPs being the most effective, followed by Lac-NCTD. As a result, Lac-NCTD-NPs may be regarded as liver-targeting agents, which combine both active and passive targeting.     

Conjugated polymer and gold nanoparticle co-loaded PLGA nanocomposites with eccentric internal nanostructure for dual-modal targeted cellular imaging

Herein is reported the one-step synthesis of an integrated nanocomposite with eccentrically loaded 5 nm gold nanoparticles (Au NPs) and conjugated polymer of poly[9,9-bis(6'-N,N,N-trimethylammonium)hexyl)fluorenyldivinylene-alt-4,7-(2,1,3,- benzothiadiazole) dibromide] (PFVBT). The nanocomposite is generated with surface-functionalized folic acid groups due to the matrix polymer of PLGA-PEG(2000) -folate used for encapsulation. The nanocomposite shows far-red fluorescence from PFVBT and scattering signal from Au NPs. Although Au NPs have been widely reported to quench the fluorescence of conjugated polymers, the PFVBT fluorescence is well maintained in the nanocomposite due to the eccentric location of Au NPs. The folic acid groups at the nanocomposite surface favor its cellular uptake by MCF-7 breast cancer cells, which have overexpressed folate receptors on the cell membranes. In conjugation with its low cytotoxicity, the folic-acid-functionalized nanocomposite has been successfully utilized for fluorescence and dark-field dual-modal targeted cellular imaging.     

Niosomes as a potential drug delivery system for increasing the efficacy and safety of nystatin

Nonionic surfactant (NIS) vesicles (niosomes) formed from self-assembly of hydrated synthetic NIS monomers are capable of entrapping a variety of drugs and have been evaluated as an alternative to liposomes. Nystatin (NYS) is a polyene antifungal drug that has been used in the treatment of cutaneous, vaginal and oral fungal infections since the 1950s. The aim of this work is to encapsulate NYS in niosomes to obtain a safe and effective formula administered parenterally for neutropenic patients. NYS niosomes were prepared by the thin-film hydration method using Span 60 or Span 40 and cholesterol (CHOL). Stearylamine and dicetyl phosphate were added as the positive and negative charge-inducing agents (CIA), respectively. Two molar ratios were used, namely NIS/CHOL/CIA (1:1:0.1 and 2:1:0.25). Neutral and positively charged niosomes gave the highest encapsulation efficiencies. NYS niosomes were characterized using transmission electron microscopy, differential scanning calorimetry and dynamic light scattering. The release of neutral and negatively charged NYS niosomes was estimated, and it showed a slow sustained release profile. A 25-kGy γ-irradiation dose was sufficient to sterilize the investigated vesicles. NYS niosomes exerted less nephrotoxicity and hepatotoxicity in vivo, showed higher level of drug in vital organs and revealed pronounced efficacy in elimination of the fungal burden in experimental animals infected with Candida albicans compared with those treated with free NYS. Niosomal encapsulation thus provided means for parenteral administration of NYS, reducing its toxicity and making it a more active antifungal agent.     

Optimization and evaluation of microwave-assisted synthesis of magnetite as a carrier for targeted drug delivery system

ABSTRACT

The present research work is a novel cost-effective method for synthesis of magnetite. Magnetite is a carrier which is used in the targeted drug delivery system. The conventional methods of preparation of magnetite take around 6–7 h for the completion of reaction; moreover, the particle size of magnetite which we get by the conventional methods is above 5 µm, so the present work aims at preparing magnetite with microwave assistance which has found to reduce reaction time with particle size obtained below 5 µm. The aim of this study was to optimize magnetite synthesis using 2³ factorial design by Design-Expert software. Magnetites were synthesized using oxidation of ferrous sulfate. In the next step, the effects of different variables on particle size are studied, including the stirring speed, microwave power (W), and stirring time. Based on the type and the variables studied, eight formulations were designed using factorial design method, and were then prepared, and their particle size was determined. Finally, selected magnetite syntheses were evaluated from the viewpoints of scanning electron microscopy (SEM) and x-ray diffraction (XRD). Results revealed that magnetite obtained from the solutions generated Design-Expert software could be selected as the best and optimized formulations due to their lowest particle size.     

Preparation of griseofulvin nanoparticle suspension by high-pressure homogenization and preservation of the suspension with saccharides and sugar alcohols

Aim: We have attempted to micronize drug particles with a particle size of less than 100 nm and maintain the particle size of their suspension to improve the solubility and bioavailability of poorly water-soluble drugs. Furthermore, the method of freeze-drying nanoparticles was applied to maintain particulate nature of nanoparticles containing various saccharides and sugar alcohols for a long time. Method: Griseofulvin (GF)–lipid nanoparticle suspension is prepared using GF and a lipid by high-pressure homogenization. The particle size of the obtained GF–lipid nanoparticle suspension is maintained constant by freeze-drying. Result: The mean particle size of GF–lipid nanoparticles prepared by high-pressure homogenization is approximately 60 nm. The mean particle size remains less than 100 nm for 1 month. The GF–lipid nanoparticle suspension containing xylitol, trehalose, or sucrose is freeze-dried to maintain the particulate nature. The mean particle size of the rehydrated suspension is lower than that of the rehydrated suspension containing erythritol or lactose. In particular, it is new knowledge to have found that an aggregation is minimized by adding xylitol which is sugar alcohol. The minimum concentration of xylitol, trehalose, and sucrose required to maintain a constant particle size by rehydration is 3%, 3%, and 5% (w/v), respectively.     

Design,characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting

Context: Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra.

Objective: The purpose of the present study was to investigate the possibility of targeting an anti-Parkinson’s drug ropinirole (RH) to the brain using polymeric nanoparticles.

Materials and methods: Ropinirole hydrochloride (RH)-loaded chitosan nanoparticles (CSNPs) were prepared by an ionic gelation method. The RH-CSNPs were characterized for particle size, polydispersity index (PDI), zeta potential, loading capacity, entrapment efficiency in vitro release study, and in vivo distribution after intranasal administration.

Results and discussion: The RH-CSNPs showed sustained release profiles for up to 18?h. The RH concentrations (% Radioactivity/g) in the brain following intranasal administration (i.n.) of RH-CSNPs were found to be significantly higher at all the time points compared with RH solution. The concentration of RH was highest in the liver (7.210?±?0.52), followed by kidneys (6.862?±?0.62), intestine (4.862?±?0.45), and lungs (4.640?±?0.92) in rats following i.n. administration of RH-CSNPs. Gamma scintigraphy imaging in rats was performed to ascertain the localization of drug in the brain following intranasal administration of formulations. The brain/blood ratios obtained (0.251?±?0.09 and 0.386?±?0.57 of RH (i.n.) and RH-CSNPs (i.n.), respectively) at 0.5?h are indicative of direct nose to brain transport, bypassing the blood–brain barrier (BBB).

Conclusion: The novel formulation showed the superiority of nose to brain delivery of RH using mucoadhesive nanoparticles compared with other delivery routes reported earlier.     

Performance characteristics of guanine incorporated PVDF-HFP/PEO polymer blend electrolytes with binary iodide salts for dye-sensitized solar cells

In this work, we have investigated the influence of guanine as an organic dopant in dye-sensitized solar cell (DSSC) based on poly(vinylidinefluoride-co-hexafluoropropylene) (PVDF-HFP)/polyethylene oxide (PEO) polymer blend electrolyte along with binary iodide salts (potassium iodide (KI) and tetrabutylammonium iodide (TBAI)) and iodine (I₂). The PVDF-HFP/KI + TBAI/I₂, PVDF-HFP/PEO/KI + TBAI/I₂ and guanine incorporated PVDF-HFP/PEO/KI + TBAI/I₂ electrolytes were prepared by solution casting technique using DMF as solvent. The PVDF-HFP/KI + TBAI/I₂ electrolyte showed an ionic conductivity value of 9.99 × 10⁻⁵ Scm⁻¹, whereas, it was found to be increased to 4.53 × 10⁻⁵ Scm⁻¹ when PEO was blended with PVDF-HFP/KI + TBAI/I₂ electrolyte. However, a maximum ionic conductivity value of 3.67 × 10⁻⁴ Scm⁻¹ was obtained for guanine incorporated PVDF-HFP/PEO/KI + TBAI/I₂ blend electrolyte. The photovoltaic properties of all these polymer electrolytes in DSSCs were characterized. As a consequence, the power conversion efficiency of the guanine incorporated PVDF-HFP/PEO/KI + TBAI/I₂ electrolyte based DSSC was significantly improved to 4.98% compared with PVDF-HFP/PEO/KI + TBAI/I₂ electrolyte based DSSC (2.46%). These results revealed that the guanine can be an effective organic dopant to enhance the performance of DSSCs.     

Preparation and evaluation of mucin-gelatin mucoadhesive microspheres for rectal delivery of ceftriaxone sodium

Soluble mucin (S-mucin) processed from the small intestines (ileal region) of freshly slaughtered pigs via homogenization, dialysis, centrifugation and lyophilization and its admixtures with type A gelatin were dispersed in an aqueous medium and used to formulate ceftriaxone sodium-loaded mucoadhesive microspheres by the emulsification cross-linking method using arachis oil as the continuous phase. The release profile of ceftriaxone sodium from the microspheres was evaluated in both simulated gastric fluid (SGF) without pepsin (pH 1.2) and simulated intestinal fluid (SIF) without pancreatin (pH 7.4). The microspheres were further evaluated as possible novel delivery system for rectal delivery of ceftriaxone sodium in rats. Release of ceftriaxone sodium from the microspheres in both release media was found to occur predominantly by diffusion following non-Fickian transport mechanism and was higher and more rapid in SIF than in SGF. The results obtained from this study may indicate that ceftriaxone sodium could be successfully delivered rectally when embedded in microspheres formulated with either type A gelatin alone or its admixtures with porcine mucin; hence providing a therapeutically viable alternative route for the delivery of this acid-labile third generation cephalosporin.     

Preparation and evaluation of gel formulations for oral sustained delivery to dysphagic patients

Background: Oral sustained release gel formulations may provide a means of administering drugs to dysphagic and geriatric patients who have difficulties with handling and taking oral dosage forms. Aim: We have designed gel formulations for the oral administration of paracetamol with suitable rheological characteristics for ease of administration to patients with swallowing difficulties and sufficient integrity in the acidic environment of the stomach to achieve a sustained release of this drug. Method: Gels formed by gelatin, agar, gellan, pectin, and xyloglucan were assessed for suitable gel strength and in vitro and in vivo release characteristics. Results: Gellan (1.5%?w/v) and xyloglucan gels (1.5%?w/w) had acceptable gel strengths for ease of swallowing and retained their integrity in the rat stomach sufficiently well to sustain the release of paracetamol over a period of 6 hours. Comparison of 1.5%?xyloglucan gels with a commercially available preparation with identical paracetamol concentrations demonstrated improved sustained release properties of the xyloglucan gels. Conclusions: Gels formed by gellan and xyloglucan have suitable rheological and sustained release characteristics for potential use as vehicles for oral delivery of drugs to dysphagic patients.     

Preparation and evaluation of in situ gelling ophthalmic drug delivery system for methazolamide

Purpose: In this study, a thermosensitive in situ gelling vehicle was prepared to increase the precorneal resident time and the bioavailability of methazolamide (MTA). Method: Poloxamer analogs were used as the gelling agents, and the in situ gel was obtained by using a cold method. The gelation temperature, rheological properties, in vitro release as well as in vivo evaluation (the elimination of MTA in aqueous humor and intraocular-lowering effect) of the optimized formulations were investigated. Results: The optimum concentrations of poloxamer analogs for the in situ gel-forming delivery system were 21% (w/w) poloxamer 407 and 10% (w/w) poloxamer P188. This formulation was able to flow freely under nonphysiological conditions and underwent sol–gel transition in the cul-de-sac upon placement into the eye. In vitro release studies demonstrated a diffusion-controlled release of MTA from the poloxamer solutions over a period of 10 hours. In vivo evaluation indicated that the poloxamer solutions had a better ability to retain drug than MTA eyedrops did. Conclusion: These results suggested that in situ gelling ophthalmic drug delivery system may hold some promise in ocular MTA delivery.     

Preparation, evaluation, and NMR characterization of vinpocetine microemulsion for transdermal delivery

A novel microemulsion was prepared to increase the solubility and the in vitro transdermal delivery of poorly water-soluble vinpocetine. The correlation between the transdermal permeation rate and structural characteristics of vinpocetine microemulsion was investigated by pulsed field gradient nuclear magnetic resonance (PFG-NMR). For the microemulsions, oleic acid was chosen as oil phase, PEG-8 glyceryl caprylate/caprate (Labrasol®) as surfactant (S), purified diethylene glycol monoethyl ether (Transcutol P®) as cosurfactant (CoS), and the double-distilled water as water phase. Pseudo-ternary phase diagrams were constructed to obtain the concentration range of each component for the microemulsion formation. The effects of various oils and different weight ratios of surfactant to cosurfactant (S/CoS) on the solubility and permeation rate of vinpocetine were investigated. Self-diffusion coefficients were determined by PFG-NMR in order to investigate the influence of microemulsion composition with the equal drug concentration on their transdermal delivery. Finally, the microemulsion containing 1% vinpocetine was optimized with 4% oleic acid, 20.5% Labrasol, 20.5% Transcutol P, and 55% double-distilled water (w/w), in which drug solubility was about 3160-fold higher compared to that in water and the apparent permeation rate across the excised rat skin was 36.4 ± 2.1 µg/cm²/h. The physicochemical properties of the optimized microemulsion were examined for the pH, viscosity, refractive index, conductivity, and particle size distribution. The microemulsion was stable after storing more than 12 months at 25°C. The irritation study showed that the optimized microemulsion was a nonirritant transdermal delivery system.     

Preparation and evaluation of polymer/clay nanocomposite surface treatments for concrete durability enhancement

In this work, the effectiveness of nanocomposite surface treatments as protective systems for concrete substrates was evaluated. The study was carried out on hybrid organic-inorganic systems prepared by solvent intercalation of an organomodified montmorillonite into two commercial resins: a coating and a pore liner. The obtained nanocomposite systems at 2, 4 and 6 wt% of nanoclay were applied on concrete substrates and characterized to evaluate their protection performances in comparison with the plain resins. In particular, the effect of the different treatments on liquid and vapor water barrier properties, salt attack resistance, porosity, surfaces water repellency and color changes were analyzed. The results demonstrated that the nanoclay addition can significantly improve the protection effectiveness of both the used plain resins, with chromatic modifications undetectable to the naked eye. However, the extent of the obtained gain strongly depends on the chemical nature and therefore on the mechanisms of action of the matrix.