Targeted Drug Delivery

The influence of physical properties and morphology of crystallised lactose on delivery of salbutamol sulphate from dry powder inhalers

by Waseem Kaialy

Drug usage, internet and criminal victimization: A socio-legal analysis

by Debarati Halder

Published in the INCDCV 2012, Proceedings of the international Conference on Exploring the Linkages between Drug Usage and Criminal victimization; ed by P. Madhava Soma Sundaram & K. Jaishankar ISBN: 978-81-906687-6-7

DENDRIMER: A NOVEL DRUG DELIVERY SYSTEM

by Ram C Dhakar

ENVIRONMENTAL RESPONSIVE HYDROGELS: A NOVEL APPROACH IN DRUG DELIVERY SYSTEM

by Ram C Dhakar

The use of a dual PEDOT and RGD-functionalized alginate hydrogel coating to provide sustained drug delivery and improved cochlear implant function

by Jennifer Chikar

Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity to MET inhibition in glioblastoma

by Robert Bradley

Because oncogene MET and EGF receptor (EGFR) inhibitors are in clinical development against several types of cancer,... more Because oncogene MET and EGF receptor (EGFR) inhibitors are in clinical development against several types of cancer, including glioblastoma, it is important to identify predictive markers that indicate patient subgroups suitable for such therapies. We investigated in vivo glioblastoma models characterized by hepatocyte growth factor (HGF) autocrine or paracrine activation, or by MET or EGFR amplification, for their susceptibility to MET inhibitors. HGF autocrine expression correlated with high phospho-MET levels in HGF autocrine cell lines, and these lines showed high sensitivity to MET inhibition in vivo. An HGF paracrine environment may enhance glioblastoma growth in vivo but did not indicate sensitivity to MET inhibition. EGFRvIII amplification predicted sensitivity to EGFR inhibition, but in the same tumor, increased copies of MET from gains of chromosome 7 did not result in increased MET activity and did not predict sensitivity to MET inhibitors. Thus, HGF autocrine glioblastoma bears an activated MET signaling pathway that may predict sensitivity to MET inhibitors. Moreover, serum HGF levels may serve as a biomarker for the presence of autocrine tumors and their responsiveness to MET therapeutics.

Optimal protection of stabilised dry live bacteria from bile toxicity in oral dosage forms by bile acid adsorbent resins

by Krishnaa Mahbubani

Edwards, A. D., Chatterjee, P., Mahbubani, K. T., Reis, C. M. and Slater, N. K.H. (2010)
Chemical Engineering Science, 65 (16) pp 4844-4854

We previously found that dried live bacteria of a vaccine strain can be temporarily sensitive to bile acids and... more We previously found that dried live bacteria of a vaccine strain can be temporarily sensitive to bile acids and suggested that Bile Adsorbing Resins (BAR) can be used in oral vaccine tablets to protect dried bacteria from intestinal bile. Here, we report a quantitative analysis of the ability of BAR to exclude the dye bromophenol blue from penetrating into matrix tablets and also sections of hard capsule shells. Based on this quantitative analysis, we made a fully optimised formulation, comprising 25% w/w of cholestyramine in Vcaps™ HPMC capsules. This gave effectively 100% protection of viability from 4% bile, with 4200-fold more live bacteria recovered from this formulation compared to unprotected dry bacteria. From the image analysis, we found that the filler material or compaction force used had no measurable effect on dye exclusion but did affect the rate of tablet hydration. Increasing the mass fraction of BAR gave more exclusion of dye up to 25% w/w, after which a plateau was reached and no further dye exclusion was seen. More effective dye exclusion was seen with smaller particle sizes (i.e. cholestyramine) and when the BAR was thoroughly dried and disaggregated. Similar results were found when imaging dye penetration into capsule sections or tablets. The predictions of the dye penetration study were tested using capsules filled with dried attenuated Salmonella vaccine plus different BAR types, and the expected protection from bile was found, validating the imaging study. Surprisingly, depending on the capsule shell material, some protection was given by the capsule alone without adding BAR, with Vcaps™ HPMC capsules providing up to 174-fold protection against 1% bile; faster releasing Vcaps Plus™ HPMC capsules and Coni Snap™ gelatin capsules gave less protection.

intracellular Caspase-Linked Chimeric Antigen Receptor

by Scott Tarone

The Chimeric Antigen Receptor (CAR), first devised by Gross et al in 1989 (1), has proven effective against cancer as... more The Chimeric Antigen Receptor (CAR), first devised by Gross et al in 1989 (1), has proven effective against cancer as well as immunosuppressive viruses. Landmark work done by Carl June M.D. et al. led to a recent clinical trial in which CD-19 specific-CAR transfected autologous T cells were reinfused to a patient with chemorefractory Chronic Lymphoid Leukemia (CLL). This patient, along with another in the same trial, achieved a complete response within 30 days and remained in remission 10 months after treatment. A specific immune system response was detected and memory effector cells were generated. The only high level toxic events were Tumor Lysis Syndrome and Hypogammaglobulinemia the later expected as the CAR was specific for CD19 which is expressed on all early B cells (2).  The historical significance of Dr. June's work notwithstanding, a limitation to this approach exists stemming from the fact that the peptide containing the epitope targeted by the CAR's variable region must exist on the surface of the tumor cells.  With the exception of hematopoietic cells, as exemplified in Dr. June's work, the peptide would preferentially be expressed only on tumor cells so off-tissue toxicity would be avoided.  An example of this, unfortunately, has occurred in another trial where a CAR specific for erbB-2 was used.  ErbB-2 is expressed on breast and colon cancer cells, but it is also found on healthy endothelial cells; one patient died just days after treatment and on-target/off-tissue events were postulated as the root cause of death (3).  I am proposing an approach that differs from the conventional in three ways: (i) directly targeting of tumor specific or associated antigens within the malignant cells with (ii) an antibody based biological agent (iii) linked to a constitutively active but inhibited form of an apoptosis effector that is released uninhibited upon the antibody binding its agonist.

Characterization and scanning electron microscopic investigation of crosslinked freeze dried gelatin matrices for study of drug diffusivity and release kinetics

by Dr. Goutam Thakur

Goutam Thakur, Analava Mitra, Amit Basak, Debdoot Sheet, Micron 43:311–320(2012)

Drug delivery is a promising technique to enhance the therapeutic efficacy of the drug. However, properties of carrier... more Drug delivery is a promising technique to enhance the therapeutic efficacy of the drug. However, properties of carrier materials require intense improvement for effective transport of drug molecules. In the current study, attempts have been made to develop freeze dried gelatin matrices cross linked with genipin at various temperatures (5ºC, 15ºC and 25ºC) prior to freeze-drying (-80ºC). The freeze dried matrices thus obtained at the said temperatures are characterized for crosslinking density, compression strength, swelling behaviors. The matrix crosslinked at 25ºC showed highest Flory Rehner crosslinking density (467±46) (p<0.05), highest compressive strength (12.36±0.12) (p<0.05) and lowest equilibrium water content. In this context, scanning electron microscopy (SEM) was performed to study the surface morphology (size and shape of pores) of the crosslinked matrices. These images were further processed for quantitative analysis of morphological features viz., areas, radius, ferret diameter, length of major and minor axis and eccentricity using MATLAB toolboxes. These quantitative analyses correlate transport and the release kinetics of model anti-inflammatory drug (indomethacin) from crosslinked matrices in vitro to tune as a controllable delivery system. The diffusional exponent (n) for all constructs ranging from 0.61-0.69 (p<0.05) (0.45<n<0.89) indicated non-Fickian release kinetics

Multifunctional human serum albumin nanoparticles for biomedical imaging and targeted drug delivery

by Bharat Kumar Reddy Karumuri

David K. Bwambok1, Kristen E. Schexnayder1, James McNamara2, Bharat Karumuri2, Mark A. DeCoster2,Leszek Malkinski1 and Matthew A. Tarr1*
1Department of Chemistry and AMRI, University of New Orleans, New Orleans, LA 70148
2Institute of Micromanufacturing, Louisiana Tech University, Ruston, LA 71270

The use of magnetic and fluorescent nanoparticles as drug delivery agents has received considerable attention due to... more The use of magnetic and fluorescent nanoparticles as drug delivery agents has received considerable attention due to the prospect of simultaneous magnetic and fluorescence imaging as well as magnetic drug release. We report the synthesis and characterization of multifunctional human serum albumin magnetic nanoparticles for potential drug delivery, biomedical imaging, and therapeutic applications. Well dispersed, spherical albumin nanoparticles with average diameter in the range of 150-250 nm were obtained as characterized using dynamic light scattering and transmission electron microscopy. We have demonstrated the incorporation of magnetic nanoparticles, fluorescent drug analogs and drugs into these human serum albumin nanoparticles. Enhanced release of the fluorescent molecules and drugs from the nanoparticles after treatment with enzymes or upon exposure to radiofrequency magnetic field have been demonstrated. The presence of magnetic nanoparticles provides the possibility of magnetic resonance tissue imaging, magnetic triggered drug release, and magnetic hyperthermia therapy. In addition, fluorescent molecules enable the use of fluorescence imaging providing for a bimodal imaging system for biomedical applications.

Similarity-Based Virtual Screening Using Bayesian Inference Network: Enhanced Search Using 2D Fingerprints and Multiple Reference Structures

by Ammar Abdo

Published in QSAR & Combinatorial Science

It has been known that different reference structure retrieve different sets of structures. Recent works in similarity... more It has been known that different reference structure retrieve different sets of structures. Recent works in similarity searching have suggested that significant improvements in retrieval effectiveness can be achieved by combining results from different reference structures. One of an important characteristic of the Bayesian inference network (BIN) model is that permits the combining of multiple reference structures. In this paper we introduce a formal inference net model to directly combine the contributions of multiple reference structures, and propose a novel approach to the combination of information from various reference structures. The inference net model of similarity, which was designed from this point of view, treats similarity searching as an evidential reasoning process where multiple sources of evidence about target structure are combined to estimate similarity scores. In this paper, we have compared BIN with other similarity searching methods when multiple bioactive reference structures are available. Six different 2D fingerprints were used in combination with data fusion (DF) and nearest neighbor (NN) approaches as search tools and also as descriptors for BIN. Our empirical results show that the BIN consistently outperformed all conventional approaches such as DF and NN, regardless of the fingerprints that were tested. The superiority of BIN over conventional approaches is ascribed to the fact that BIN understands the content of the descriptors of the structures and references and used this understanding to infer the direct relationship between structures and references.

Bayesian Inference Network Significantly Improves the Effectiveness of Similarity Searching Using Multiple 2D Fingerprints and Multiple Reference Structures

by Ammar Abdo

Published in "QSAR & Combinatorial Science Journal, Wiley, 2009"

Recent work in similarity searching have suggested that significant improvements in retrieval effectiveness can be... more Recent work in similarity searching have suggested that significant improvements in retrieval effectiveness can be achieved by combining results from multiple reference structures or multiple molecular descriptors. Recently, the Bayesian inference network model (BIN) has been introduced for performing molecular similarity searching using a single and multiple reference structures. One of the important characteristics of the inference network model is that it permits the combination of multiple reference structures and multiple molecular descriptors. This paper introduces an inference network model developed for molecular similarity searching that integrates into a single framework, multiple reference structures and multiple molecular descriptors. The inference network model of similarity, which was designed from this point of view, treats similarity searching as an evidential reasoning process where multiple sources of evidence about reference and compound content are combined to estimate similarity scores. Our results show that, the BIN with multiple descriptors is notably more effective than BIN with a single descriptor in searches for structurally diverse sets of actives molecules.

Multiple Bubble Resonance in a Tube

by Marissa Braverman

Tackling Problem Drug Use: A New Conceptual Framework

by Julian Buchanan

Journal of Social Work in Mental Health (The Haworth Social Work Practice Press, an imprint of The Haworth Press, Inc.) Vol. 2, No. 2/3, 2004, pp. 117-138;

Successful ‘recovery’ from long-term problem drug use has depended largely upon understanding and tackling the... more Successful ‘recovery’ from long-term problem drug use has depended largely upon understanding and tackling the physiological and psychological nature of drug dependence; however, drawing upon research and practice in Liverpool, England, the author questions whether this discourse is sufficient given the changing nature, context and attitudes towards drug consumption in the twenty-first century. This article emphasises the importance of incorporating structural and social factors. Drawing upon qualitative data from three separate studies, the author illustrates how stigmatisation, marginalisation, and social exclusion are significant debilitating components that have tended to be overlooked. This paper contributes new insights into the damaging impact of political rhetoric and structural discrimination that has placed many long-term drug users vulnerable to relapse. In response to these findings the author offers a new conceptual framework for practice that incorporates and pro-motes an understanding of the social nature and context of long-term drug dependence.

Rethinking Substance Misuse Policy & Practice in Wales (2010)

by Julian Buchanan

This is an 'Ideas Wales Discussion Paper' on Crime and Criminal Justice - one of a series of discussion papers that... more This is an 'Ideas Wales Discussion Paper' on Crime and Criminal Justice - one of a series of discussion papers that have been prepared and published on the Ideas Wales website http://www.ideaswales.org.uk/publications.htm which seeks to generate new ideas to help inform the policy challenges of the future. This paper explores Substance Misuse Policy: http://www.ideaswales.org.uk/documents/Ideas%20Wales%20%20-%20Substance%20Misuse.pdf