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1.
Eiichi Yamamoto Kenji Hyodo Takuya Suzuki Hiroshi Ishihara Hiroshi Kikuchi Masaru Kato 《Pharmaceutical research》2018,35(5):103
Purpose
To simulate the stimuli-responsive and stoichiometrically controlled doxorubicin (DOX) release from liposomes in in vivo tumor interstitial fluid (TIF), the effect of ammonia concentration and pH on the DOX release from liposomes in human plasma at 37°C was quantitatively evaluated in vitro and the release rate was calculated as a function of ammonia concentration and pH.Methods
Human plasma samples spiked with DOX-loaded PEGylated liposomes (PLD) or Doxil®, containing ammonia (0.3–50 mM) at different pH values, were incubated at 37°C for 24 h. After incubation, the concentration of encapsulated DOX in the samples was determined by validated solid-phase extraction (SPE)-SPE-high performance liquid chromatography.Results
Accelerated DOX release (%) from liposomes was observed as the increase of ammonia concentration and pH of the matrix, and the decrease of encapsulated DOX concentration. The release rate was expressed as a function of the ammonia concentration and pH by using Henderson-Hasselbalch equation.Conclusions
The DOX release from PLD in TIF was expressed as a function ammonia concentration and pH at various DOX concentrations. Further, it was found that the DOX release from liposomes in a simulated TIF was more than 15 times higher than in normal plasma.2.
Kinda A. Darwish Yahya Mrestani Hans-Hermann Rüttinger Reinhard H. H. Neubert 《Pharmaceutical research》2016,33(5):1175-1181
Purpose
Is to characterize the drug release from the ß-cyclodextrin (ß-CD) cavity and the drug transfer into model membranes by affinity capillary electrophoresis. Phospholipid liposomes with and without cholesterol were used to mimic the natural biological membrane.Methods
The interaction of cationic and anionic drugs with ß-CD and the interaction of the drugs with liposomes were detected separately by measuring the drug mobility in ß-CD containing buffer and liposome containing buffer; respectively. Moreover, the kinetics of drug release from ß-CD and its transfer into liposomes with or without cholesterol was studied by investigation of changes in the migration behaviours of the drugs in samples, contained drug, ß-CD and liposome, at 1:1:1 molar ratio at different time intervals; zero time, 30 min, 1, 2, 4, 6, 8, 10 and 24 h. Lipophilic drugs such as propranolol and ibuprofen were chosen for this study, because they form complexes with ß-CD.Results
The mobility of the both drug liposome mixtures changed with time to a final state. For samples of liposomal membranes with cholesterol the final state was faster reached than without cholesterol.Conclusions
The study confirmed that the drug release from the CD cavity and its transfer into the model membrane was more enhanced by the competitive displacement of the drug from the ß-CD cavity by cholesterol, the membrane component. The ACE method here developed can be used to optimize the drug release from CD complexes and the drug transfer into model membranes.3.
Purpose
Although doxorubicin (DXR) has been on the market for many years as an anti-cancer drug, a number of serious dose-limiting toxicities hinder its widespread use. To reduce the known toxicities of soluble DXR, various liposomes have been designed including Doxil, Caelyx, and Myocet. Myocet, a non-PEGylated liposomal formulation containing DXR, was found to reduce the toxicities associated with soluble DXR and has been used in Europe and Canada (but not the US) as a first line therapy. While regarded as successful, Myocet does have some formulation drawbacks including stability, drug release, and an arduous formulation and remote loading method for preparation.Methods
Our lab has developed a liposomal electrospray process in which formulation and remote loading occurs continuously in one step, cutting down on the total time of production and increasing the drug retention in the liposomes with respect to more conventional methods. Electrosprayed Myocet-like liposomes were then tested in vitro for release kinetics and cytotoxicity with respect to a more conventional formulation method.Results
Myocet-like liposomes manufactured via electrospray had similar DXR loadings, hydrodynamic diameters, morphologies, and cytotoxic profiles as their thin-film hydration counterparts, but their release profiles were drastically prolonged.Conclusions
Our findings indicate that electrospray is a viable manufacturing procedure to scalably produce Myocet-like liposomes that appear to be more stable than those formulated through thin-film hydration.4.
Yun Yang Ji Wang Hongliang He Wenli Zhang Yuansheng Zhang Jianping Liu 《Pharmaceutical research》2018,35(7):134
Purpose
Spherical reconstituted high density lipoprotein (rHDL) can target atherosclerotic lesions by the very low density lipoprotein (VLDL) receptor, which is seldom expressed in liver. By promoting this pathway, the targeting efficiency was hyphothesized to be improved due to avoiding undesired uptake in liver mediated by the scavenger receptor class B type I (SR-BI). In this study, how fatty acid modification in spherical rHDL influenced the VLDL receptor-mediated endocytosis pathway was investigated.Methods
Stearic acid (SA) and arachidonic acid (AA) with different saturation levels were utilized to modify the lovastatin-loaded rHDL (LS-rHDL). Phagocytosis test on foam cells with or without cholesteryl ester transfer protein (CETP) expression was conducted to observe the cellular uptake of the SA or AA modified rHDL and the non-modified one. Raman spectroscopy, guanidine hydrochloride (Gdn-HCl) denaturation experiment and in vitro evaluation of drug release were used to analyze the related mechanism.Results
In comparison with the non-modified rHDL, AA modification could reduce the packing order of the rHDL phospholipid acyl chains, leading to the decreased apoA-I binding extent with lipid and the increased drug release, while the opposite was true for SA modification. The AA-modified rHDL exhibited a higher uptake of foam cells expressing CETP than the non-modified one, while the SA-modified one showed the lowest cellular uptake among the three rHDLs.Conclusions
Increased unsaturation level can facilitate lipid-interchange process where the cargo in rHDL core may transfer to VLDL more easily, and then promote the endocytosis mediated by the VLDL receptor.5.
Daniela Monti Silvia Tampucci Erica Zucchetti Carlotta Granchi Filippo Minutolo Anna Maria Piras 《Pharmaceutical research》2018,35(9):175
Purpose
The inhibitors of the human isoform 5 of lactate dehydrogenase (hLDH5) have attracted growing interest as efficient anti-cancer agents. In the present paper, the interactions between an efficient hLDH5 inhibitor (N-hydroxyindole-2-carboxylic derivative) and lipid bilayers based on dipalmitoylphosphatidylcholine (DPPC) were investigated. Additionally, since interstitial acidification plays a key role in tumor pathogenesis and tumor drug therapy, the effect of acidic pH was assessed and correlated to DPPC/drug interaction.Methods
Four different techniques were used: differential scanning calorimetry, dynamic light scattering, UV-VIS second derivative spectrometry and attenuated total reflection Fourier transformed infrared spectroscopy.Results
All techniques concur in highlighting a structural change of lipid assembly, susceptible both to pH change and to the presence of the antitumor compound. Lipid vesicles appeared more compact at the lower pH, since the thermal pre-transition from the lamellar gel phase to the ripple gel phase was absent at pH 7.4 and the infrared analysis revealed a stronger acyl chain packing as well as a different hydration degree. Drug interaction was mainly detected in the lipid region including the ester linkages and the first portion of the acyl chains. Furthermore, a lower drug partitioning was recorded at pH 6.6.Conclusions
The investigated antitumor agent possesses a stable negative charge at the investigated pH values, thus the lower interaction at the acidic pH is mainly ascribable to an environmental effect on lipid assembly. Therefore, drug efficacy under tumor acid conditions may be hampered by the observed lipid membrane constraints, and suggest for the development of suitable prodrugs.6.
Purpose
Liposomes have been developed as versatile nanocarriers for various pharmacological agents. The effect of surface charges on the cellular uptake of the liposomes has been studied by various methods using mainly fixed cells with inevitable limitations. Live cell imaging has been proposed as an alternative methods to overcome the limitations of the fixed cell-based analysis. In this study, we aimed to investigate the effects of surface charges on cellular association and internalization of the liposomes using live cell imaging.Methods
We studied the cellular association and internalization of liposomes with different surface charge using laser scanning confocal microscopy (LSCM) equipped with live cell chamber system. Flow cytometry was also carried out using flow cytometer (FACS) for comparison.Results
All of the cationic, neutral and anionic liposomes showed time-dependent cellular uptake through specific endocytic pathways. In glioblastoma U87MG cells, the cationic and anionic liposomes were mainly taken up via macropinocytosis, while the neutral liposomes mainly via caveolae-mediated endocytosis. In fibroblast NIH/3T3 cells, all of the three liposomes entered into the cell via clathrin-mediated endocytosis.Conclusions
This study provides a better understanding on the cellular uptake mechanisms of the liposomes, which could contribute significantly to development of liposome-based drug delivery systems.7.
Jasmin Monpara Chryso Kanthou Gillian M. Tozer Pradeep R. Vavia 《Pharmaceutical research》2018,35(4):90
Purpose
This work explores synthesis of novel cholesterol derivative for the preparation of cationic liposomes and its interaction with Paclitaxel (PTX) within liposome membrane using molecular dynamic (MD) simulation and in-vitro studies.Methods
Cholesteryl Arginine Ethylester (CAE) was synthesized and characterized. Cationic liposomes were prepared using Soy PC (SPC) at a molar ratio of 77.5:15:7.5 of SPC/CAE/PTX. Conventional liposomes were composed of SPC/cholesterol/PTX (92:5:3 M ratio). The interaction between paclitaxel, ligand and the membrane was studied using 10 ns MD simulation. The interactions were studied using Differential Scanning Calorimetry (DSC) and Small Angle Neutron Scattering analysis. The efficacy of liposomes was evaluated by MTT assay and endothelial cell migration assay on different cell lines. The safety of the ligand was determined using the Comet Assay.Results
The cationic liposomes improved loading efficiency and stability compared to conventional liposomes. The increased PTX loading could be attributed to the hydrogen bond between CAE and PTX and deeper penetration of PTX in the bilayer. The DSC study suggested that inclusion of CAE in the DPPC bilayer eliminates Tg. SANS data showed that CAE has more pronounced membrane thickening effect as compared to cholesterol. The cationic liposomes showed slightly improved cytotoxicity in three different cell lines and improved endothelial cell migration inhibition compared to conventional liposomes. Furthermore, the COMET assay showed that CAE alone does not show any genotoxicity.Conclusions
The novel cationic ligand (CAE) retains paclitaxel within the phospholipid bilayer and helps in improved drug loading and physical stability.Graphical Abstract ?
8.
Lingli Zhou Liu Yang Chulei Yang Yi Liu Qiuyue Chen Wenli Pan Qing Cai Lifeng Luo Lu Liu Shan Jiang Haibing He Yu Zhang Tian Yin Xing Tang 《Pharmaceutical research》2018,35(7):147
Purpose
This work aims to create a novel Cu2+ liposome with excellent loading stability and develop synergistic effect with disulfiram (DSF) for the treatment of tumor.Methods
Copper oleate was incorporated into the liposome membrane via alcohol injection method in this work. In vitro release test was applied to evaluate the release profile of the liposomes. Pharmacokinetic studies were performed in rats and the antitumor efficacy was assessed in mice bearing hepatoma xenografts.Results
The copper oleate liposome (Cu(OI)2-L) was formulated and the loading efficiency were more than 85%. TEM images confirmed that the Cu(OI)2-L had a spherical morphology with an average diameter of 100 nm. Cu(OI)2-L displayed a biphasic release profile, with >70% retained drug over 8 h incubation in PBS at pH 7.4. Pharmacokinetic studies demonstrated that Cu(OI)2-L had a prolonged circulation time and increased AUC when compared to the injection of copper oleate solution. The antitumor efficacy test demonstrated an enhanced tumor inhibition rate with the treatment of Cu(OI)2-L and DSF nanoparticles, indicating an improved synergistic antitumor effect.Conclusions
The Cu(OI)2-L was suitable to be employed in combination with disulfiram for tumor treatment and can also open up opportunities for targeted delivery of copper.9.
Purpose
Volume of distribution is an important pharmacokinetic parameter in the distribution and half-life of a drug. Protein binding and lipid partitioning together determine drug distribution.Methods
Here we present a simple relationship that estimates the volume of distribution with the fraction of drug unbound in both plasma and microsomes. Model equations are based upon a two-compartment system and the experimental fractions unbound in plasma and microsomes represent binding to plasma proteins and cellular lipids, respectively.Results
The protein and lipid binding components were parameterized using a dataset containing human in vitro and in vivo parameters for 63 drugs. The resulting equation explains ~84% of the variance in the log of the volume of distribution with an average fold-error of 1.6, with 3 outliers.Conclusions
These results suggest that Vss can be predicted for most drugs from plasma protein binding and microsomal partitioning.10.
Shaoning?Wang Shihui?Yu Yuwei?Lin Peizhi?Zou Guihong?Chai Heidi?H.?Yu Hasini?Wickremasinghe Nivedita?Shetty Junhong?Ling Jian?Li Qi??Zhou 《Pharmaceutical research》2018,35(10):187
Purpose
This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa.Methods
Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate gradient. Particle size, encapsulation efficiency, in vitro drug release and in vitro antibiotic activities were evaluated.Results
The optimized liposomal formulation has uniform sizes of approximately 100 nm, with encapsulation efficiency of 67.0% (for colistin) and 85.2% (for ciprofloxacin). Incorporation of anionic lipid (DMPG) markedly increased encapsulation efficiency of colistin (from 5.4 to 67.0%); however, the encapsulation efficiency of ciprofloxacin was independent of DMPG ratio. Incorporation of colistin significantly accelerated the release of ciprofloxacin from the DMPG anionic liposomes. In vitro release of ciprofloxacin and colistin in the bovine serum for 2 h were above 70 and 50%. The cytotoxicity study using A549 cells showed the liposomal formulation is as non-toxic as the drug solutions. Liposomal formulations of combinations had enhanced in vitro antimicrobial activities against multidrug resistant P. aeruginosa than the monotherapies.Conclusions
Liposomal formulations of two synergistic antibiotics was promising against multidrug resistant P. aeruginosa infections.11.
Shima Gholizadeh Emmy M. Dolman Rebecca Wieriks Rolf W. Sparidans Wim E. Hennink Robbert J. Kok 《Pharmaceutical research》2018,35(4):85
Purpose
Sepantronium bromide (YM155) is a hydrophilic quaternary compound that cannot be administered orally due to its low oral bioavailability; it is furthermore rapidly eliminated via the kidneys. The current study aims at improving the pharmacokinetic profile of YM155 by its formulation in immunoliposomes that can achieve its enhanced delivery into tumor tissue and facilitate uptake in neuroblastoma cancer cells.Methods
PEGylated YM155 loaded liposomes composed of DPPC, cholesterol and DSPE-PEG2000 were prepared via passive film-hydration and extrusion method. Targeted (i.e. immuno-)liposomes were prepared by surface functionalization with SATA modified monoclonal anti-disialoganglioside (GD2) antibodies. Liposomes were characterized based on their size, charge, antibody coupling and YM155 encapsulation efficiency, and stability. Flow cytometry analysis and confocal microscopy were performed on IMR32 and KCNR neuroblastoma cell lines. The efficacy of developed formulations were assessed by in-vitro toxicity assays. A pilot pharmacokinetic analysis was performed to assess plasma circulation and tumor accumulation profiles of the developed liposomal formulations.Results
YM155 loaded immunoliposomes had a size of 170 nm and zeta potential of ?10 mV, with an antibody coupling efficiency of 60% andYM155 encapsulation efficiency of14%. Targeted and control liposomal formulations were found to have similar YM155 release rates in a release medium containing 50% serum. An in-vitro toxicity study on KCNR cells showed less toxicity for immunoliposomes as compared to free YM155. In-vivo pharmacokinetic evaluation of YM155 liposomes showed prolonged blood circulation and significantly increased half-lives of liposomal YM155 in tumor tissue, as compared to a bolus injection of free YM155.Conclusions
YM155 loaded immunoliposomes were successfully formulated and characterized, and initial in-vivo results show their potential for improving the circulation time and tumor accumulation of YM155.12.
Purpose
Acute lung injury (ALI) is a fatal syndrome in critically ill patients. It is characterized by lung edema and inflammation. Numerous pro-inflammatory mediators are released into alveoli. Among them, interleukin-1beta (IL-1β) causes an increase in solute permeability across the alveolar-capillary barrier leading to edema. It activates key effector cells (alveolar epithelial and endothelial cells) releasing inflammatory chemokines and cytokines. The purpose of the study was to demonstrate that nebulized liposomes inhibit ALI in vivo.Methods
In vivo ALI model was simulated through intra-tracheal instillation of IL-1β solution (100 μg/mL in PBS, pH 7.2, 200 μL) in male Sprague-Dawley rats. Various formulations were tested in ALI induced rats. These formulations include plain liposomes (PL), methylprednisolone sodium succinate solution (MPS solution), cRGD-peptide grafted liposomes (LcRGD) and methylprednisolone sodium succinate encapsulated and cRGD-peptide grafted liposomes (MPS-LcRGD). Formulations were nebulized in vivo in rats using micro-pump nebulizer.Results
Liposome formulations exhibited higher levels of drug concentration in lungs. The physicochemical parameters demonstrated that the liposome formulations were stable. On the basis of aerodynamic droplet-size, nebulized formulations were estimated to deposit in different regions of respiratory tract, especially alveolar region, Among the formulations, MPS-LcRGD caused significant reduction of edema, neutrophil infiltration and inflammation biochemical marker levels.Conclusion
From the results, it can be inferred that nebulization of targeted liposomes had facilitated spatial and temporal modulation of drug delivery resulting in alleviation of ALI.13.
Purpose
Abundance of receptors on tumor vasculature presents a prominent target for theranostic applications. The alphavbeta3 integrin receptors expressed on vascular endothelial cells during angiogenesis were therefore considered targets for imaging. Non-invasive visualization of tumor growth and/or delivery systems can appreciate tumor localization and disposition kinetics of carriers, respectively. Herein, we report near-infrared fluorescence imaging (NIRFI) of solid tumors using targeted fluorescence nanoliposomes in vivo.Methods
Fluorescence nanoliposomes surface modified with cRGD-peptide were injected into CD1 athymic (nu/nu) mice bearing C6 glioblastoma xenografts (300 mm3). At different time points, mice were subjected to NIRFI for visualization of tumor xenografts and nanocarrier tracing in vivo.Results
NIRFI showed tumor localization of 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indotricarbocyanine iodide (DiR18)-incorporated-targeted liposomes with maximum tumor-to-tissue occurring at 24-h post-liposome administration. Interaction of integrin receptors with targeted liposomes had contributed to an intense NIRF signal. Molecular studies showed an elevated expression of alphavbeta3 integrin receptors in tumor xenografts.Conclusion
From the studies, it can be concluded that non-invasive localization of tumors and tracing of liposome carriers had been achieved using receptor targeting and NIRFI approaches.14.
Bilyana M. Dicheva Ann L. B. Seynhaeve Thomas Soulie Alexander M. M. Eggermont Timo L. M. ten Hagen Gerben A. Koning 《Pharmaceutical research》2016,33(3):627-638
Purpose
To evaluate pharmacokinetic profile, biodistribution and therapeutic effect of cationic thermosensitive liposomes (CTSL) encapsulating doxorubicin (Dox) upon mild hyperthermia (HT).Methods
Non-targeted thermosensitive liposomes (TSL) and CTSL were developed, loaded with Dox and characterized. Blood kinetics and biodistribution of Dox-TSL and Dox-CTSL were followed in B16BL6 tumor bearing mice upon normothermia (NT) or initial hyperthermia conditions. Efficacy study in B16BL6 tumor bearing mice was followed with Dox-TSL or Dox-CTSL upon NT or HT. Efficacy study in LLC tumor bearing mice was performed upon two HT conditions. Intravital microscopy was performed on B16BL6 tumors implanted in dorsal-skin fold window-bearing mice.Results
Targeting did not cause faster blood clearance of CTSL compared to TSL. Highest uptake of liposomes was observed in spleen, kidneys and liver. Applying HT prior to CTSL administration increased drug delivery to the tumor and CTSL delivered ~1.7 fold higher Dox concentration compared to TSL. Efficacy in B16BL6 murine melanoma showed that HT had a significant effect on CTSL in tumor suppression and prolonged survival. Efficacy in LLC Lewis lung carcinoma tumor model demonstrates that two HT treatments hold promises for a successful treatment option.Conclusion
CTSL have potency to increase drug efficacy in tumors due to their targeted and drug release functions.15.
Jinyuan Ma Hongjie Wu Yang Li Zehua Liu Guihua Liu Yuxin Guo Zhenqing Hou Qingliang Zhao Dengyue Chen Xuan Zhu 《Pharmaceutical research》2018,35(3):57
Purpose
This work was intended to develop novel doxorubicin (DOX)/zinc (II) phthalocyanine (ZnPc) co-loaded mesoporous silica (MSNs)@ calcium phosphate (CaP)@PEGylated liposome nanoparticles (NPs) that could efficiently achieve collaborative anticancer therapy by the combination of photodynamic therapy (PDT) and chemotherapy. The interlayer of CaP could be utilized to achieve pH-triggered controllable drug release, promote the cellular uptake, and induce cell apoptosis to further enhance the anticancer effects.Methods
MSNs were first synthesized as core particles in which the pores were diffusion-filled with DOX, then the cores were coated by CaP followed by the liposome encapsulation with ZnPc to form the final DOX/ZnPc co-loaded MSNs@CaP@PEGylated liposome.Results
A core-interlayer-shell MSNs@CaP@PEGylated liposomes was developed as a multifunctional theranostic nanoplatform. In vitro experiment indicated that CaP could not only achieve pH-triggered controllable drug release, promote the cellular uptake of the NPs, but also generate high osmotic pressure in the endo/lysosomes to induce cell apoptosis. Besides, the chemotherapy using DOX and PDT effect was achieved by the photosensitizer ZnPc. Furthermore, the MSNs@CaP@PEGylated liposomes showed outstanding tumor-targeting ability by enhanced permeability and retention (EPR) effect.Conclusions
The novel prepared MSNs@CaP@PEGylated liposomes could serve as a promising multifunctional theranostic nanoplatform in anticancer treatment by synergic chemo-PDT and superior tumor-targeting ability.16.
Taro Shimizu Amr S. Abu Lila Mizuki Awata Yukiyo Kubo Yu Mima Yosuke Hashimoto Hidenori Ando Keiichiro Okuhira Yu Ishima Tatsuhiro Ishida 《Pharmaceutical research》2018,35(11):223
Purpose
Immunogenicity of PEGylated proteins and nanomedicines represents a potential impediment against their development and use in clinical settings. The purpose of this study is to develop a method for detecting anti-PEG immunity of PEGylated proteins and/or nanomedicines using flow cytometry.Methods
The binding of fluorescence-labeled mPEG-modified liposomes to HIK-G11 cells, PEG-specific hybridoma cells, or spleen cells was evaluated by flow cytometry for detecting immunogenicity of PEGylated therapeutics.Results
The fluorescence-labeled methoxy PEG (mPEG)-modified liposomes were efficiently bound to HIK-G11 cells. Such staining with fluorescence-labeled mPEG-modified liposomes was significantly inhibited in the presence of either non-labeled mPEG-modified liposomes or mPEG-modified ovalbumin (OVA) but not polyglycerol-modified liposomes. In addition, we found that mPEG-modified liposomes, highly immunogenic, caused proliferation of PEG-specific cells, while hydroxyl PEG-modified liposomes, less immunogenic, scarcely caused. Furthermore, after intravenous injection of mPEG-modified liposomes, the percentage of PEG-specific cells in the splenocytes, as determined by flow cytometry, corresponded well with the production level of anti-PEG antibodies, as determined by ELISA.Conclusions
PEG-specific B cell assay we introduced may become a useful method to detect an anti-PEG immune response against PEGylated therapeutics and clarify the mechanism for anti-PEG immune responses.17.
Antony V. Samrot Ujjala Burman Padmanaban S P. Yamini Arul Maximus Rabel 《Toxicology and Environmental Health Sciences》2018,10(3):162-167
Objective
To evaluate the toxicity of the silver nanoparticle against earthworms - Eudrilus eugeniae, a model for soil organism.Methods
Silver nanoparticles were synthesised by chemical reduction and further characterised by UV Visible Spectroscopy and FeSEM. Earthworms were allowed to interact with different concentrations of the synthesized silver nanoparticles. After exposure period, histology and inductively coupled plasma optical emission spectrometry (ICP-OES) were done to determine the accumulation and toxic effects exhibited by the nanoparticle on earthworms.Results
The synthesized nanoparticle was found to be between the size of 180 and 200 nm. Histology studies revealed that silver nanoparticles to cause fibrosis, lipofuscin-like deposits and also gut disruption in earthworms.Conclusion
Silver nanoparticles were found to be toxic to Eudrilus eugeniae, which was evidenced by histology.18.
Bhushan S. Pattni Srikar G. Nagelli Bhawani Aryasomayajula Pranali P. Deshpande Abhijit Kulkarni William C. Hartner Ganesh Thakur Alexei Degterev Vladimir P. Torchilin 《Pharmaceutical research》2016,33(10):2540-2551
Purpose
To develop transferrin (Tf)-targeted delivery systems for the pro-apoptotic drug, NCL-240, and to evaluate the efficacy of this delivery system in ovarian cancer NCI/ADR-RES cells, grown in vitro in a 3D spheroid model.Methods
Tf-targeted PEG-PE-based micellar and ePC/CHOL-based liposomal delivery systems for NCL-240 were prepared. NCI/ADR-RES cells were used to generate spheroids by a non-adhesive liquid overlay technique. Spheroid growth and development were monitored by size (diameter) analysis and H&E staining. The targeted formulations were compared to untargeted ones in terms of their degree of spheroid association and penetration. A cell viability analysis with NCL-240-loaded micelles and liposomes was performed to assess the effectiveness of Tf-targeting.Results
Tf-targeted polymeric micelles and Tf-targeted liposomes loaded with NCL-240 were prepared. NCI/ADR-RES cells generated spheroids that demonstrated the presence of a distinct necrotic core along with proliferating cells in the spheroid periphery, partly mimicking in vivo tumors. The Tf-targeted micelles and liposomes had a deeper spheroid penetration as compared to the untargeted delivery systems. Cell viability studies using the spheroid model demonstrated that Tf-mediated targeting markedly improved the cytotoxicity profile of NCL-240.Conclusion
Transferrin targeting enhanced delivery and effectiveness of micelles and liposomes loaded with NCL-240 against NCI/ADR-RES cancer cells in a 3D spheroid model.19.
Purpose
Pulmonary infection namely tuberculosis is characterized by alveolar macrophages harboring a large microbe population. The chitosan nanoparticles exhibit fast extracellular drug release in aqueous biological milieu. This study investigated the matrix effects of chitosan nanoparticles on extracellular drug diffusion into macrophages.Methods
Oligo, low, medium and high molecular weight chitosan nanoparticles were prepared by nanospray drying technique. These nanoparticles were incubated with alveolar macrophages in vitro and had model drug sodium fluorescein added into the same cell culture. The diffusion characteristics of sodium fluorescein and nanoparticle behavior were investigated using fluorescence microscopy, scanning electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy techniques.Results
The oligochitosan nanoparticles enabled macrophage membrane fluidization with the extent of sodium fluorescein entry into macrophages being directly governed by the nanoparticle loading. Using nanoparticles made of higher molecular weight chitosan, sodium fluorescein permeation into macrophages was delayed due to viscous chitosan diffusion barrier at membrane boundary.Conclusion
Macrophage-chitosan nanoparticle interaction at membrane interface dictates drug migration into cellular domains.20.