David Needham

Overview:

Professor Needham also holds appointments as Associate Professor of Biomedical Engineering; Associate Professor, Center for Bioinspired materials and material Systems, and the Center for Biomolecular and Tissue Engineering; and Associate Professor, Duke Comprehensive Cancer Center.

Needham's Lab uses a platform technology of micropipette manipulation to manipulate single and pairs of micro particles in order to assess their behavior in well defined fluids and excipient concentrations. He brings a wealth of expertise in micromanipulation, colloid stability, and drug delivery formulation.

Dr. Needham's research program combines the fields of Materials Science with Colloid and Surface Chemistry focusing on "Biological and other Soft Wet Materials."

The program is in the general area of forming, coating and encapsulation of solid, liquid and gaseous particles in the colloidal size range (10 nanometers to 10 micrometers). It deals more specifically with the material properties of 2-phase micro and nanosystems, such as surfactants, lipid monolayers, lipid bilayer membranes, micelles, liposomes, hydrogels, wax particles, emulsions, microdroplets, gas bubbles, microcrystals, microglasses, polymer microspheres, and blood and cancer cells.

It is also concerned with the adhesion and repulsion between particle surfaces involving molecular structures at interfaces including repulsive interactions due to the presence of grafted water-soluble polymers and specific interactions between receptors-ligand pairs. Such materials property measurements and inter particle interactions require specialized experimental equipment and the principal experimental approach is that of micropipet manipulation, to manipulate individual and pairs of micro particles and cells in controlled solution environments.

Previous NIH/NCI research grants, focused on experiments and theory concerning:
  1. Molecular exchange and defect formation in lipid vesicle membranes, (specifically involving the partitioning of amphipathic molecules like surfactants, drugs, pH sensitive polymers, and fusogenic peptides); and 
  2. Novel thermally sensitive drug delivery system for treatment of solid tumors. 
Research topics currently under investigation include: lipid and surfactant monolayers at gas bubble, and liquid emulsion surfaces; diffusion-solubility, crystallization and solidification of polymers, lipids, proteins, inorganic crystals and drugs from 2 phase Microsystems, including degradable PLGA polymer microspheres.

The latter is currently funded through an NIH grant entitled, "Microsphere Engineering for Proteins as Drugs". Particular applications of these materials and materials processing concepts are in drug delivery, specifically, the temperature-triggered drug release in solid tumors, and lately formulations of more hydrophobic drugs as emulsions and of proteins in polymer microspheres. Information gained in this work is directed towards, for example, improved image contrast agents, drug delivery systems that use lipids and polymers to create micro- and nano-capsules and monolayer coatings.

The Temperature-sensitive liposome systems are being tested pre-clinically and now clinically with collaborators in the Duke Medical Center, specifically with Dr. Mark Dewhirst in Radiation Oncology. New research is focusing on organic-inorganic nano composites derived from simple surfactants, and new bilayer model systems for studying and using single protein channel activity with Collaborators at Oxford University in the United Kingdom.

Positions:

Professor in the Department of Mechanical Engineering and Materials Science

Mechanical Engineering and Materials Science
Pratt School of Engineering

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1975

Nottingham Trent University (United Kingdom)

Ph.D. 1981

University of Nottingham (United Kingdom)

Grants:

Graduate training in Biologically Inspired Materials

Administered By
Pratt School of Engineering
Awarded By
National Science Foundation
Role
Co-Principal Investigator
Start Date
End Date

Development and Construction of Single Molecule Spectrometers for Research and Student Training

Administered By
Mechanical Engineering and Materials Science
Awarded By
National Science Foundation
Role
Co-Principal Investigator
Start Date
End Date

TRP and AQP Channels: Modulation of Function, Raft Location by Membrane Lipids

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Consultant
Start Date
End Date

PLGA Protein Microspheres: Single Particle Engineering

Administered By
Pratt School of Engineering
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Faculty Development Workshop: "Course Enhancement Projects" Across the Pratt Curriculum

Administered By
Mechanical Engineering and Materials Science
Awarded By
Lord Foundation of North Carolina
Role
Principal Investigator
Start Date
End Date

Publications:

Polymer Microparticles with Defined Surface Chemistry and Topography Mediate the Formation of Stem Cell Aggregates and Cardiomyocyte Function.

Surface-functionalized microparticles are relevant to fields spanning engineering and biomedicine, with uses ranging from cell culture to advanced cell delivery. Varying topographies of biomaterial surfaces are also being investigated as mediators of cell-material interactions and subsequent cell fate. To investigate competing or synergistic effects of chemistry and topography in three-dimensional cell cultures, methods are required to introduce these onto microparticles without modification of their underlying morphology or bulk properties. In this study, a new approach for surface functionalization of poly(lactic acid) (PLA) microparticles is reported that allows decoration of the outer shell of the polyesters with additional polymers via aqueous atom transfer radical polymerization routes. PLA microparticles with smooth or dimpled surfaces were functionalized with poly(poly(ethylene glycol) methacrylate) and poly[N-(3-aminopropyl)methacrylamide] brushes, chosen for their potential abilities to mediate cell adhesion. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry analysis indicated homogeneous coverage of the microparticles with polymer brushes while maintaining the original topographies. These materials were used to investigate the relative importance of surface chemistry and topography both on the formation of human immortalized mesenchymal stem cell (hiMSCs) particle-cell aggregates and on the enhanced contractility of cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs). The influence of surface chemistry was found to be more important on the size of particle-cell aggregates than topographies. In addition, surface chemistries that best promoted hiMSC attachment also improved hiPSC-CM attachment and contractility. These studies demonstrated a new route to obtain topo-chemical combinations on polyester-based biomaterials and provided clear evidence for the predominant effect of surface functionality over micron-scale dimpled topography in cell-microparticle interactions. These findings, thus, provide new guiding principles for the design of biomaterial interfaces to direct cell function.
Authors
Alvarez-Paino, M; Amer, MH; Nasir, A; Cuzzucoli Crucitti, V; Thorpe, J; Burroughs, L; Needham, D; Denning, C; Alexander, MR; Alexander, C; Rose, FRAJ
MLA Citation
Alvarez-Paino, Marta, et al. “Polymer Microparticles with Defined Surface Chemistry and Topography Mediate the Formation of Stem Cell Aggregates and Cardiomyocyte Function.Acs Applied Materials & Interfaces, vol. 11, no. 38, Sept. 2019, pp. 34560–74. Epmc, doi:10.1021/acsami.9b04769.
URI
https://scholars.duke.edu/individual/pub1451443
PMID
31502820
Source
epmc
Published In
Acs Applied Materials & Interfaces
Volume
11
Published Date
Start Page
34560
End Page
34574
DOI
10.1021/acsami.9b04769

Adsorption of ionic surfactants at microscopic air-water interfaces using the micropipette interfacial area-expansion method: Measurement of the diffusion coefficient and renormalization of the mean ionic activity for SDS.

The dynamic adsorption of ionic surfactants at air-water interfaces have been less-well studied than that of the simpler non-ionics since experimental limitations on dynamic surface tension (DST) measurements create inconsistencies in their kinetic analysis. Using our newly designed "Micropipette interfacial area-expansion method", we have measured and evaluated both equilibrium and dynamic adsorption of a well-known anionic surfactant, sodium dodecyl sulphate (SDS), in the absence or presence of 100mM NaCl. Our focus was to determine if and to what extent the inclusion of a new correction parameter for the "ideal ionic activity", A±i, can renormalize both equilibrium and dynamic surface tension measurements and provide better estimates of the diffusion coefficient of ionic surfactants in aqueous media obtained from electroneutral models, namely extended Frumkin isotherm and Ward-Tordai adsorption models. We found that the estimated value of the new parameter, A±i=0.29, is key to obtain the diffusion coefficient D=5.3±0.3×10-6cm2/s for SDS, in excellent agreement with the literature. These new technique and analyses can now be applied to study the interfacial adsorption of a range of both ionic and non-ionic surface-active molecules, including the potentially slower-diffusing polymers and biological materials like lipids, peptides, and proteins.
Authors
Kinoshita, K; Parra, E; Needham, D
MLA Citation
URI
https://scholars.duke.edu/individual/pub1262175
PMID
28623702
Source
epmc
Published In
Journal of Colloid and Interface Science
Volume
504
Published Date
Start Page
765
End Page
779
DOI
10.1016/j.jcis.2017.05.077

Microglassification™: a novel technique for protein dehydration.

The dehydration of biologics is commonly employed to achieve solid-dose formulation and enhanced stability during long-term preservation. We have developed a novel process, Microglassification™, which can rapidly and controllably dehydrate protein solutions into solid amorphous microspheres at room temperature. Single bovine serum albumin (BSA) microdroplets were suspended in pentanol or decanol using a micropipette, and the dynamic changes in droplet dissolution were observed in real-time and correlated to protein's water of hydration, medium's water activity, and microsphere protein concentration. Microglassification™ was also carried out at bulk scale, and changes in BSA secondary structure were analyzed by Fourier transform infrared spectroscopy and fluorescence spectroscopy; multimer formation was detected by native gel electrophoresis. BSA concentration in the microsphere increased with solvent exposure time and decreasing water activity. Image analysis at single particle and bulk scale showed the formation of solid BSA microspheres with a maximum protein concentration of 1147 ± 32 mg/mL. The native BSA samples were dehydrated to approximately 450 waters per BSA, which is well below monolayer coverage of 1282 waters per BSA. The secondary structure of Microglassified™ BSA reverted to native-like conformation upon rehydration with only minor irreversible aggregation (2.7%). Results of the study establish the efficacy of the Microglassification™ for the successful dehydration of biologics.
Authors
Aniket,; Gaul, DA; Rickard, DL; Needham, D
MLA Citation
Aniket, Tong H., et al. “Microglassification™: a novel technique for protein dehydration.Journal of Pharmaceutical Sciences, vol. 103, no. 3, Mar. 2014, pp. 810–20. Epmc, doi:10.1002/jps.23847.
URI
https://scholars.duke.edu/individual/pub1005315
PMID
24415208
Source
epmc
Published In
Journal of Pharmaceutical Sciences
Volume
103
Published Date
Start Page
810
End Page
820
DOI
10.1002/jps.23847

Comparative effects of thermosensitive doxorubicin-containing liposomes and hyperthermia in human and murine tumours.

PURPOSE: In previous reports, laboratory-made lysolecithin-containing thermosensitive liposome encapsulating doxorubicin (LTSL-DOX) showed potent anticancer effects in FaDu human squamous cell carcinoma. To further study the spectrum of LTSL-DOX activity, the efficacy of its commercial formulation was re-examined in FaDu and compared in HCT116, PC3, SKOV-3 and 4T07 cancer cell lines. Factors that may influence differences in HT-LTSL-DOX efficacy were also examined. METHODS: Anticancer effect was measured using standard growth delay methods. We measured doubling time and clonogenic survival after doxorubicin exposure in vitro, and interstitial pH and drug concentrations in vivo. RESULTS: In all five tumour types, HT-LTSL-DOX increased median tumour growth time compared with untreated controls (p < 0.0006) and HT alone (p < 0.01), and compared with LTSL-DOX alone in FaDu, PC-3 and HCT-116 (p < 0.0006). HT-LTSL-DOX yielded significantly higher drug concentrations than LTSL-DOX (p < 0.0001). FaDu was most sensitive (p < 0.0014) to doxorubicin (IC(50) = 90 nM) in vitro, compared to the other cell lines (IC(50) = 129-168 nM). Of the parameters tested for correlation with efficacy, only the correlation of in vitro doubling time and in vivo median growth time was significant (Pearson r = 0.98, p = 0.0035). Slower-growing SKOV-3 and PC-3 had the greatest numbers of complete regressions and longest tumour growth delays, which are clinically important parameters. CONCLUSIONS: These results strongly suggest that variations in anti-tumour effect of HT-LTSL-DOX are primarily related to in vitro doubling time. In the clinic, the rate of tumour progression must be considered in design of treatment regimens involving HT-LTSL-DOX.
Authors
Yarmolenko, PS; Zhao, Y; Landon, C; Spasojevic, I; Yuan, F; Needham, D; Viglianti, BL; Dewhirst, MW
MLA Citation
Yarmolenko, Pavel S., et al. “Comparative effects of thermosensitive doxorubicin-containing liposomes and hyperthermia in human and murine tumours.Int J Hyperthermia, vol. 26, no. 5, 2010, pp. 485–98. Pubmed, doi:10.3109/02656731003789284.
URI
https://scholars.duke.edu/individual/pub744422
PMID
20597627
Source
pubmed
Published In
Int J Hyperthermia
Volume
26
Published Date
Start Page
485
End Page
498
DOI
10.3109/02656731003789284

A mathematical model for the spread of morphogens with density dependent chemosensitivity

Authors
Merkin, JH; Needham, DJ; Sleeman, BD
MLA Citation
Merkin, J. H., et al. “A mathematical model for the spread of morphogens with density dependent chemosensitivity.” Nonlinearity, vol. 18, no. 6, IOP Publishing, Nov. 2005, pp. 2745–73. Crossref, doi:10.1088/0951-7715/18/6/018.
URI
https://scholars.duke.edu/individual/pub681621
Source
crossref
Published In
Nonlinearity
Volume
18
Published Date
Start Page
2745
End Page
2773
DOI
10.1088/0951-7715/18/6/018