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Mondal L, Mukherjee B, Das K, et al. Int J Nanomedicine. 2019;14:8073–8094.The authors have advised due to an error at the time of figure assembly, Figure 5 on page 8085 is incorrect. The correct Figure 5 is shown below. The authors apologize for this error and advise it does not affect the results of the paper.Read the original article

Laboni Mondal,1 Biswajit Mukherjee,1 Kaushik Das,2 Sanchari Bhattacharya,1 Debasmita Dutta,1 Shreyasi Chakraborty,1 Murari Mohan Pal,1 Raghuvir H Gaonkar,3 Mita Chatterjee Debnath3 1Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India; 2Department of Biological Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, India; 3Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, IndiaCorrespondence: Biswajit MukherjeeDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaTel +91 332 457 2588Fax +91 332 414 6677Email biswajit.mukherjee@jadavpuruniversity.inBackground and objective: Targeted drug delivery of nanoparticles decorated with site-specific recognition ligands is of considerable interest to minimize cytotoxicity of chemotherapeutics in the normal cells. The study was designed to develop CD-340 antibody-conjugated polylactic-co-glycolic acid (PLGA) nanoparticles loaded with a highly water-soluble potent anticancer drug, doxorubicin (DOX), to specifically deliver entrapped DOX to breast cancer cells.Methods: The study showed how to incorporate water-soluble drug in a hydrophobic PLGA (85:15) based matrix which otherwise shows poor drug loading due to leaching effect. The optimized formulation was covalently conjugated to anti-human epidermal growth factor receptor-2 (HER2) antibody (CD-340). Surface conjugation of the ligand was assessed by flow cytometry, confocal microscopy, and gel electrophoresis. Selectivity and cytotoxicity of the experimental nanoparticles were tested on human breast cancer cells SKBR-3, MCF-7, and MDA-MB-231. Both CD-340-conjugated and unconjugated nanoparticles were undergone in vitro and in vivo characterization.Result: Higher level of incorporation of DOX (8.5% W/W), which otherwise shows poor drug loading due to leaching effect of the highly water-soluble drug, was seen in this method. In HER2-overexpressing tumor xenograft model, radiolabeled antibody-conjugated nanoparticles showed preferentially more of the formulation accumulation in the tumor area when compared to the treatments with the unconjugated one or with the other control groups of mice. The ligand conjugated nanoparticles showed considerable potential in reduction of tumor growth and cardiac toxicity of DOX in mice, a prominent side-effect of the drug.Conclusion: In conclusion, CD-340-conjugated PLGA nanoparticles containing DOX preferentially delivered encapsulated drug to the breast cancer cells and in breast tumor and reduced the breast tumor cells by apoptosis. Site-specific delivery of the formulation to neoplastic cells did not affect normal cells and showed a drastic reduction of DOX-related cardiotoxicity.Keywords: breast cancer, nanoparticles, ligand, targeting, tumor

Ruma Maji, Niladri Shekhar Dey, Bhabani Sankar Satapathy, Biswajit Mukherjee, Subhasish MondalDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata (Calcutta), IndiaBackground: Four formulations of Tamoxifen citrate loaded polylactide-co-glycolide (PLGA) based nanoparticles (TNPs) were developed and characterized. Their internalization by Michigan Cancer Foundation-7 (MCF-7) breast cancer cells was also investigated.Methods: Nanoparticles were prepared by a multiple emulsion solvent evaporation method. Then the following studies were carried out: drug-excipients interaction using Fourier transform infrared spectroscopy (FTIR), surface morphology by field emission scanning electron micro­scopy (FESEM), zeta potential and size distribution using a Zetasizer Nano ZS90 and particle size analyzer, and in vitro drug release. In vitro cellular uptake of nanoparticles was assessed by confocal microscopy and their cell viability (%) was studied.Results: No chemical interaction was observed between the drug and the selected excipients. TNPs had a smooth surface, and a nanosize range (250–380 nm) with a negative surface charge. Drug loadings of the prepared particles were 1.5%±0.02% weight/weight (w/w), 2.68%±0.5% w/w, 4.09%±0.2% w/w, 27.16%±2.08% w/w for NP1–NP4, respectively. A sustained drug release pattern from the nanoparticles was observed for the entire period of study, ie, up to 60 days. Further, nanoparticles were internalized well by the MCF-7 breast cancer cells on a concentration dependent manner and were present in the cytoplasm. The nucleus was free from nanoparticle entry. Drug loaded nanoparticles were found to be more cytotoxic than the free drug.Conclusion: TNPs (NP4) showed the highest drug loading, released the drug in a sustained manner for a prolonged period of time and were taken up well by the MCF-7 breast cancer cell line in vitro. Thus the formulation may be suitable for breast cancer treatment due to the good permeation of the formulation into the breast cancer cells.Keywords: polylactide-co-glycolide nanoparticle, PLGA, breast cancer, multiple emulsion

Sumit Basu,1,2 Biswajit Mukherjee,1 Samrat Roy Chowdhury,1 Paramita Paul,1 Rupak Choudhury,3 Ajeet Kumar,1 Laboni Mondal,1 Chowdhury Mobaswar Hossain,1 Ruma Maji11Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India; 2Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA; 3Department of Biochemistry, Ballygunge Science College, Kolkata, IndiaObjective: We describe the development, evaluation, and comparison of colloidal gold-loaded, poly(d,l-lactic-co-glycolic acid)-based nanoparticles containing anti-acquired immunodeficiency syndrome drug stavudine and uptake of these nanoparticles by macrophages in vitro.Methods: We used the following methods in this study: drug-excipient interaction by Fourier transform infrared spectroscopy, morphology of nanoparticles by field-emission scanning electron microscopy, particle size by a particle size analyzer, and zeta potential and polydispersity index by a zetasizer. Drug loading and in vitro release were evaluated for formulations. The best formulation was incorporated with fluorescein isothiocyanate. Macrophage uptake of fluorescein isothiocyanate nanoparticles was studied in vitro.Results: Variations in process parameters, such as speed of homogenization and amount of excipients, affected drug loading and the polydispersity index. We found that the drug was released for a prolonged period (over 63 days) from the nanoparticles, and observed cellular uptake of stavudine nanoparticles by macrophages.Conclusion: Experimental nanoparticles represent an interesting carrier system for the transport of stavudine to macrophages, providing reduced required drug dose and improved drug delivery to macrophages over an extended period. The presence of colloidal gold in the particles decreased the drug content and resulted in comparatively faster drug release.Keywords: stavudine, poly(d,l-lactic-co-glycolic acid), nanoparticles, colloidal gold, uptake by macrophages

Background: Acute disseminated Encephalo Myelitis (ADEM) is an important neurological cause of mortality and morbidity and many aspects of the aetiopathogenesis and clinical presentation are still not clear. More studies are needed to be continued particularly from developing countries on ADEM. Aims & Objects: To study the clinical spectrum of ADEM in relation to aetiology and neuroimaging study and to compare the findings observed in the other parts of India and abroad. Materials and Methods: Clinical examinations, neuroimaging study and electrophysiological tests and follow up in 62 patients of ADEM in the Bangur Institute of Neurology, Kolkata, India from January 1996 to March 2004. Results: Thirty Four patients (54.83%) were below 20 years. Among the preceding events, presumptive viral infections accounted for 32.25% of the total cases, specific viral infections in 43.54% cases, and sample antirabies vaccinations in 24.19% cases. Myeloradiculitis were the common neuroparalytic complications following semple anti rabies vaccination found in 10 patients and in another 5 post vaccinated patients had multiple sites of involvement. Acute cerebellar ataxia was the common clinical presentation following varicella infection found in 8 cases and another 6 cases had multiple sites involvement. Multimodal evoked potential studies corresponds to the clinical localization of lesions. MRI studies disclosed that white matter lesions were maximum in subcortical white matter and periventricular regions. No signal alterations were observed in 4 cases of acute cerebellar ataxia following varicellar infection and 4 cases of Myeloradiculitis following semple anti rabies vaccinations. Out of 62 patients, 50 patients survived (80.64%), among them 22 patients (44%) had significant motor disability and rest 28 (56%) recovered well in the functional status. Mortality found in the study was in 12 patients (19.36%). Conclusion: Specific viral infections is the common preceding events of ADEM followed by presumptive viral and survivors had motor disability in the 44% cases. The outcome was greatly influenced by antecedent events and number of sites of involvement.

Hot and rotating exotic 124Ce nucleus near proton drip line has been populated through fusion evaporation reaction of 32S and 92Mo. This exotic nucleus was de-excited by evaporating p, n, α and/or light nuclei etc and several exotic nuclei have been populated. The experimentally obtained relative population of those exotic nuclei have been compared with the statistical model calculation. Agreement between experimental and statistical model calculation have been observed for most of the evaporation channels. Huge enhancement in comparison to statistical model calculation have been observed fora few channels related to multiple proton evaporation which could not be explained by using default and modified input parameters in statistical calculation.

AimsTo examine the associations between endogenous sex steroid hormones (oestradiol, testosterone and sex hormone-binding globulin) with diabetes risk in a South-Asian population living in the USA.MethodsWe used data from the Metabolic Syndrome and Atherosclerosis in South-Asians Living in America pilot study. The analytical sample included 60 women and 45 men of Asian Indian origin living in the San Francisco Bay Area, who were free from diabetes and cardiovascular disease and did not use exogenous sex steroids. Sex steroid hormone levels were assessed by validated conventional radioimmunoassays, and visceral and hepatic adiposity were assessed by computed tomography. We used multivariable regression to examine the association between endogenous sex steroid hormone levels (log-transformed) and fasting glucose and 2-h glucose levels in a series of sex-stratified models adjusted for age, waist circumference, visceral and hepatic adiposity, and insulin resistance.ResultsIn age-adjusted models, lower levels of sex hormone-binding globulin (β = -0.18, 95% CI -0.30, -0.06) and higher levels of free testosterone (β = 0.14, 95% CI 0.02, 0.26) were associated with elevated fasting glucose levels in South-Asian women, whereas lower levels of sex hormone-binding globulin (β = -0.14, 95% CI -0.26, -0.02) and lower levels of total testosterone (β = -0.12, 95% CI -0.24, 0.00) were associated with elevated fasting glucose levels in South-Asian men. Adjustment for waist circumference, visceral adiposity and insulin resistance attenuated most of these associations, while adjustment for hepatic adiposity strengthened some of the observed associations. Similar results were found for 2-h glucose levels.ConclusionsResults were consistent with previous research, which suggests that endogenous sex steroid hormones are a risk factor for diabetes across multiple race/ethnic groups. Additional studies are needed to determine whether visceral fat is a mediator or confounder of associations between sex steroid hormone and glucose levels.

Cloud-computing services are provided to consumers through a network of servers and network equipment. Cloud-network (CN) providers virtualize resources [e.g., virtual machine (VM) and virtual network (VN)] for efficient and secure resource allocation. Disasters are one of the worst threats for CNs as they can causemassive disruptions andCN disconnection. A disaster may also induce post-disaster correlated, cascading failures which can disconnect more CNs. Survivable virtual-network embedding (SVNE) approaches have been studied to protect VNs against single physicallink/- node and dual physical-link failures in communication infrastructure, but massive disruptions due to a disaster and their consequences can make SVNE approaches insufficient to guarantee cloud-computing survivability. In this work, we study the problem of survivable CN mapping from disaster. We consider risk assessment, VM backup location, and post-disaster survivability to reduce the risk of failure and probability of CN disconnection and the penalty paid by operators due to loss of capacity.We formulate the proposed approach as an integer linear program and study two scenarios: a natural disaster, e.g., earthquake and a human-made disaster, e.g., weapons-of-mass-destruction attack. Our illustrative examples show that our approach reduces the risk of CN disconnection and penalty up to 90% compared with a baseline CNmapping approach and increases the CN survivability up to 100% in both scenarios. © 2014 Springer Science+Business Media New York.

The Passive Optical Network (PON) is an attractive solution forhigh-bandwidth access networks. In the context of a broadband access network, the term open access implies the ability of multiple service providers to share the deployed access network infrastructure to make services available to the end users. Multiple services may thereby be delivered over a shared access channel. Open access requires fairness in terms of throughput, delay, jitter, and other network parameters in the access channel among the sharing entities, namely service providers and end users. Since the traffic in an access network is very bursty, an access network may be frequently subjected to high loads for certain durations of time. Meeting the above fairness requirements under suchconditions is therefore very challenging. In this study, we first motivate the problem of meeting fairness requirements simultaneously to both service providers and users, which are located at opposite ends of an access channel.We then investigate the importance of two different sets of Service-LevelAgreements (SLAs), which we call Dual SLAs. After formulating a mathematical model, we propose an efficient scheduling algorithm to meet Dual SLAs which is based on the well-known concept of max-min fairness. We then demonstrate the effectiveness of our proposed algorithm through simulations using a discrete-event-simulator-based PON set-up, which compares the fairness of the Dual-SLA scheduling algorithm with that of other traditional fair queuing algorithms such as Deficit Round Robin (DRR).

In this paper, we propose and investigate the characteristics of a fair queueing with service envelopes (FQSE) algorithm-a hierarchical fair-share scheduling algorithm for access networks based on a remote scheduling system such as Ethernet passive optical networks (EPON) or cable TV network. FQSE is designed to overcome the limiting factors of a typical remote scheduling system such as large control-plane delay, limited control-plane bandwidth, and significant queue switch-over overhead. The algorithm is based on a concept of service envelope - a function representing the fair allocation of resources based on a global network condition called satisfiability parameter (SP). We define properties of cousin-fairness and sibling-fairness and show the FQSE to be cousin-fair. FQSE is unique in that it is the only hierarchical algorithm that is simultaneously cousin-fair. Furthermore, we show the necessary techniques to adapt FQSE to variable-sized packet-based networks. We analyze FQSE performance in EPON serving 1024 independent queues and demonstrate FQSE's ability to provide guaranteed bandwidth to each queue and to share the excess bandwidth fairly.