BD Technologies

Lake Park, NC, United States

BD Technologies

Lake Park, NC, United States
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Pettis R.J.,BD Technologies | Harvey A.J.,BD Technologies
Therapeutic Delivery | Year: 2012

The concept of microneedle drug delivery was described three decades ago; however, effective clinical demonstration has only occurred within the past 10-15 years. Substantial progress in microneedle design and fabrication including extensive in vitro, ex vivo, and in vivo preclinical evaluation with various drugs, vaccines and other agents has transpired over the last decade. In contrast with this large volume of preclinical data, there are relatively few published microneedle clinical studies. To date, the clinical investigative focus has included testing to reduce dermal barrier properties and enhance transdermal delivery; evaluation of enhanced vaccine antigenicity, including development of the first commercial microneedle product for intradermal influenza vaccination; evaluation of altered microneedle protein pharmacokinetics and pharmacodynamics, especially for insulin; and evaluation of the pain and other perceptions associated with microneedle usage. This review summarizes the various aspects of microneedle clinical evaluation to date and identifies areas requiring further clinical evaluation. © 2012 Future Science Ltd.

Quagliata L.,Universitatsmedizin Mannheim | Klusmeier S.,Karlsruhe Institute of Technology | Cremers N.,Universitatsmedizin Mannheim | Pytowski B.,Imclone Systems | And 6 more authors.
Clinical and Experimental Metastasis | Year: 2014

For many types of human cancer, the expression of vascular endothelial growth factor-C (VEGF-C) correlates with enhanced tumor-associated lymphatic vessel density, metastasis formation and poor prognosis. In experimental animals, VEGF-C produced by primary tumors can induce lymphangiogenesis within and/or at the periphery of the tumor, and promotes metastasis formation. Tumor-induced lymphangiogenesis is therefore thought to expedite entry of tumor cells into the lymphatic vasculature and their trafficking to regional lymph nodes, thereby fostering metastatic dissemination. Tumour-produced VEGF-C can also drain to the regional lymph nodes and induce lymphangiogenesis there. Whether this activity promotes metastasis formation remains unclear. To address this issue we manipulated VEGF-C activity and VEGFR-3 activation in the lymph nodes draining syngeneic rat breast cancers using intra-dermal delivery of either recombinant VEGF-C or VEGFR-3 blocking antibodies to induce or suppress lymph node lymphangiogenesis, respectively. Recombinant VEGF-C induced lymph node lymphangiogenesis, but was not sufficient to promote metastasis formation by poorly metastatic NM-081 breast tumours. Conversely, inhibition of lymph node lymphangiogeneis induced by highly metastatic MT-450 breast tumours suppressed the outgrowth of lymph node metastases, but not the initial colonization of the lymph nodes. Lung metastasis was also not affected. We conclude that tumor-derived VEGF-C draining to regional lymph nodes promotes the outgrowth of lymph node metastases. VEGF-C may induce lung metastasis independently of its effects on lymph node metastasis. © Springer Science+Business Media 2013.

Crapnell K.,BD Technologies | Blaesius R.,BD Technologies | Hastings A.,BD Technologies | Lennon D.P.,Skeletal Research Center | And 3 more authors.
Experimental Cell Research | Year: 2013

The presence of serum in cell culture medium presents an obstacle to safe and efficient production of hMSCs for therapeutic purposes. Availability of defined medium will be crucial to elucidating the mechanism of action of hMSCs in many indications as well as a prerequisite to consistently produce cells with predictable performance characteristics.Using a bioinformatics driven approach, which we call the BD Discovery Platform, we have developed a novel serum-free medium that supports highly efficient growth while maintaining the surface markers and functional characteristics defining hMSCs. In a comparison with serum-containing and other commercially available serum-free formulations, all conditions led to expansion of cells that meet the minimal criteria for hMSCs as set by the International Society for Cellular Therapy (ISCT). However, differences in growth characteristics and gene expression patterns suggest that expansion in serum-free growth conditions can provide greater yields in a shorter time. The mRNA expression profile observed in cells grown without serum suggests upregulation of several genes implicated in hMSC function as well as downregulation of the proinflammatory cytokine IL6. © 2013 Elsevier Inc.

Laube B.L.,Johns Hopkins University | Laube B.L.,David M Rubenstein Child Health Building | Sharpless G.,Johns Hopkins University | Shermer C.,BD Technologies | And 3 more authors.
Pharmaceutical Research | Year: 2010

Purpose: To quantify distribution of albuterol aerosol generated by a pneumatic nebulizer within the nose and lungs of a model of a 9-month-old child (SAINT) and aerosol loss to the environment, during simulated breathing at increasing tidal volumes (TVs). Methods: 99mtechnetium-labeled albuterol aerosol was generated by an IPI nebulizer with face-mask. Deposition was quantified as a percentage of emitted dose using gamma scintigraphy. Results: Lung deposition was similar for all TVs, averaging 7.17±0.01%, 9.34±0.01% and 9.41±0.02% at 50, 100 and 200 mL TV, respectively. In contrast, nose deposition increased significantly with TV, averaging 4.40±0.02%, 11.39±0.02% and 22.12±0.02% at 50 mL, 100 mL and 200 mL TV, respectively (all p<0.0167). Aerosol loss to the environment was significantly lower at 200 mL TV (53.81±0.04%), compared to 50 mL (71.99±0.02%) (p<0.0167). Conclusions: Our results suggest that nasal deposition of albuterol aerosol generated by a pneumatic nebulizer in 9-month-old infants may be significantly affected by changes in TV, ranging between 50 to 200 mL, whereas total lung deposition may not be affected. These results also predict that environmental losses would be highest when administering to a child breathing at 50 mL TV. These data should be useful to companies who are working to improve aerosol delivery systems to treat infants. © 2010 Springer Science+Business Media, LLC.

Laube B.L.,Johns Hopkins University | Sharpless G.,Johns Hopkins University | Shermer C.,BD Technologies | Sullivan V.,BD Technologies | Powell K.,BD Technologies
Aerosol Science and Technology | Year: 2012

Purpose: To quantify deposition of 99mtechnetium-labeled powder in the Sophia Anatomical Infant Nose-Throat (SAINT) model of a 9-month old. Methods: Powder was generated by the Solovent (BD Technologies), an active dry powder inhaler with spacer, during 30 seconds of tidal volume (TV) breathing. Activity that passed through the model was captured on a filter and represented powder that was available for deposition in the lungs. Deposition in the nasal cavity, on the filter, and in the spacer was expressed as a percentage of the injected dose into the spacer. Results: Mean (±SD) injected dose averaged 89.5 ± 0.09%, 90.3 ± 0.11%, and 91.3 ± 0.05% at 50, 100, and 200 mL TV, respectively. Mean nasal deposition increased significantly from 50 mL to 100 mL and 200 mL TV with 0.60 ± 0.002%, 1.72 ± 0.007%, and 6.75 ± 07.21%, respectively (all p ≤ 0.05). Similarly, mean filter deposition increased significantly from 50 mL to 100 mL to 200 mL with 0.28 ± 0.00%, 1.14 ± 0.00%, and 3.87 ± 0.01%, respectively (all p < 0.05). Mean retention in the spacer was similar at 50 mL (93.38 ± 0.02%) and at 100 mL TV (89.97 ± 0.04%), but decreased significantly to 71.47 ± 0.05% at 200 mL TV (all p < 0.05). Conclusions: These data suggest for the first time the feasibility of delivering a dry powder formulation to infants and toddlers by actively introducing the powder into a spacer. Lung deposition and nasal deposition, as a percent of injected dose, were dependent on tidal volume with deposition increasing with increasing TV. Nevertheless, deposition, as a percent of injected dose, was low in both regions. This was likely due to significant retention in the spacer at all 3 tidal volumes.© 2012 Copyright Taylor and Francis Group, LLC.

Danas K.,Laboratoire Of Mecanique Des Solides | Kankanala S.V.,BD Technologies | Kankanala S.V.,Ford Motor Company | Triantafyllidis N.,Laboratoire Of Mecanique Des Solides | Triantafyllidis N.,University of Michigan
Journal of the Mechanics and Physics of Solids | Year: 2012

Magnetorheological elastomers (MREs) are ferromagnetic particle impregnated rubbers whose mechanical properties are altered by the application of external magnetic fields. Due to their coupled magnetoelastic response, MREs are finding an increasing number of engineering applications. In this work, we present a combined experimental and theoretical study of the macroscopic response of a particular MRE consisting of a rubber matrix phase with spherical carbonyl iron particles. The MRE specimens used in this work are cured in the presence of strong magnetic fields leading to the formation of particle chain structures and thus to an overall transversely isotropic composite. The MRE samples are tested experimentally under uniaxial stresses as well as under simple shear in the absence or in the presence of magnetic fields and for different initial orientations of their particle chains with respect to the mechanical and magnetic loading direction. Using the theoretical framework for finitely strained MREs introduced by Kankanala and Triantafyllidis (2004), we propose a transversely isotropic energy density function that is able to reproduce the experimentally measured magnetization, magnetostriction and simple shear curves under different prestresses, initial particle chain orientations and magnetic fields. Microscopic mechanisms are also proposed to explain (i) the counterintuitive effect of dilation under zero or compressive applied mechanical loads for the magnetostriction experiments and (ii) the importance of a finite strain constitutive formulation even at small magnetostrictive strains. The model gives an excellent agreement with experiments for relatively moderate magnetic fields but has also been satisfactorily extended to include magnetic fields near saturation. © 2011 Elsevier Ltd. All rights reserved.

Weidemaier K.,BD Technologies | Lastovich A.,BD Technologies | Keith S.,BD Technologies | Pitner J.B.,BD Technologies | And 3 more authors.
Biosensors and Bioelectronics | Year: 2011

We report here the first pre-clinical demonstration of continuous glucose tracking by fluorophore-labeled and genetically engineered glucose/galactose binding protein (GGBP). Acrylodan-labeled GGBP was immobilized in a hydrogel matrix at the tip of a small diameter optical fiber contained in a stainless steel needle. The fiber optic biosensors were inserted subcutaneously into Yucatan and Yorkshire swine, and the sensor response to changing glucose levels was monitored at intervals over a 7-day period. Sensor mean percent error on day 7 was 16.4 ± 5.0% using a single daily reference blood glucose value to calibrate the sensor. The GGBP sensor's susceptibility to common interferents was tested in a well-plate system using human sera. No significant interference was observed from the tested interferents except for tetracycline at the drug's maximum plasma concentration. The robust performance of the GGBP-based fiber optic sensor in swine models and resistance to interferents indicates the potential of this technology for continuous glucose monitoring in humans. © 2011 Elsevier B.V.

Woods R.J.,BD Technologies | Alarcon J.,BD Technologies | McVey E.,BD Technologies | Pettis R.J.,BD Technologies
Journal of Diabetes Science and Technology | Year: 2012

Background: Aggregation of insulin into insoluble fibrils (fibrillation) may lead to complications for diabetes patients such as reduced insulin potency, occlusion of insulin delivery devices, or potentially increased immunological potential. Even after extensive investigation of fibril formation in regular human insulin, there are little published data about the intrinsic fibrillation of fast-acting analogs. This article investigates and compares the intrinsic fibrillation of three fast-acting insulin analogs - lispro, aspart, and glulisine - as a function of their primary protein structure and exclusive of the stabilizing excipients that are added to their respective commercial formulations. Methods: The insulin analogs underwent a bufer exchange into phosphate-bufered saline to remove formulation excipients and then were heated and agitated to characterize intrinsic fibrillation potentials devoid of excipient stabilizing efects. Diferent analytical methods were used to determine the amount of intrinsic fibrillation for the analogs. After initial lag times, intrinsic fibrillation was detected by an amyloid-specific stain. Precipitation of insulin was confirmed by ultraviolet analysis of soluble insulin and gravimetric measurement of insoluble insulin. Electron microscopy showed dense fibrous material, with individual fibrils that are shorter than typical insulin fibrils. Higher resolution kinetic analyses were carried out in 96-well plates to provide more accurate measures of lag times and fibril growth rates. Results: All three analogs exhibited longer lag times and slower intrinsic fibrillation rates than human insulin, with glulisine and lispro rates slower than aspart. This is the first study comparing the intrinsic fibrillation of fast-acting insulin analogs without the stabilizing excipients found in their commercial formulations. Conclusions: Data show diferent intrinsic fibrillation potentials based on primary molecular structures when the formulation excipients that are critical for stability are absent. Understanding intrinsic fibrillation potential is critical for evaluating insulin analog stability and device compatibility. © Diabetes Technology Society.

Teska B.M.,Aurora Pharmaceutical | Alarcon J.,BD Technologies | Pettis R.J.,BD Technologies | Randolph T.W.,University of Colorado at Boulder | Carpenter J.F.,Aurora Pharmaceutical
Journal of Pharmaceutical Sciences | Year: 2014

The stability of three commercial "fast-acting" insulin analogs, insulin lispro, insulin aspart, and insulin glulisine, was studied at various concentrations of phenolic preservatives (phenol and/or meta-cresol) during 9 days of incubation at 37C. The analysis by both size-exclusion and reversed-phase chromatography showed degradation of lispro and aspart that was inversely dependent on the concentration of phenolic preservatives. Insulin glulisine was much more stable than the other analogs and showed minimal degradation even in the absence of phenolic preservatives. With sedimentation velocity ultracentrifugation, we determined the preservatives' effect on the insulins' self-assembly. When depleted of preservatives, insulin glulisine dissociates from higher molecular weight species into a number of intermediate molecular weight species, in between monomer and hexamer, whereas insulin aspart and insulin lispro dissociate into monomers and dimers. Decreased stability of insulin lispro and insulin aspart seems to be because of the extent of dissociation when depleted of preservative. Insulin glulisine's dissociation to intermediate molecular weight species appears to help minimize its degradation during incubation at 37C. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2255-2267, 2014 © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Harvey A.J.,BD Technologies | Kaestner S.A.,BD Technologies | Sutter D.E.,BD Technologies | Harvey N.G.,BD Technologies | And 2 more authors.
Pharmaceutical Research | Year: 2011

Purpose: The purpose of this research was to examine the pharmacokinetics (PK) of drug uptake for microneedle-based intradermal (ID) delivery of several classes of protein drugs compared to standard subcutaneous (SC) administration. Methods: Systemic absorption kinetics of various proteins were analyzed following microneedle-based ID delivery and standard injection methods in the swine model. Comparative PK data were determined using standard non-compartmental techniques based on blood serum levels. Results: Delivery of proteins using microneedles resulted in faster systemic availability, measured via t max, and increased maximal drug concentration, C max, over SC delivery for all proteins tested. Some agents also exhibited increased bioavailability for the ID route. Imaging studies using reporter dyes showed rapid lymphatic-mediated uptake. Conclusions: Microneedle delivery is applicable to a wide variety of protein drugs and is capable of effective parenteral administration of therapeutic drug dosages. This delivery route alters absorption kinetics via targeting a tissue bed better perfused with lymphatic and blood vessels than the SC space. Microneedle delivery may afford various advantages, including a robust method to increase the absorption rate and bioavailability of proteins that have been challenging to deliver at therapeutic levels or with physiologically relevant profiles. © 2010 Springer Science+Business Media, LLC.

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