Duke University, NC, USA and University of Nottingham, UK
Advanced drug delivery formulations
I lead the Laboratory-to-Clinic Translational Research and Development for Cancer (LCTRDC) resource established in 2018 by a Strategic Development Fund grant from the University of Nottingham. With many anti-cancer drugs not able to be delivered effectively because of their poor water solubility, the so-called “Bricks of the pharmaceutical industry”, in a complete paradigm shift, we have created even less-soluble prodrug therapeutics that can form new endogenous-inspired nanoparticle designs for treating brain and other cancers including metastases. The goal of our resource is to bring this unique “Bricks-to-Rocks” technologies from Duke University to Nottingham and engage, across UoN and the Medical School and especially in the CBTRC, basic scientific, pharmaceutical, preclinical and clinical researchers in an effort to bring repurposed and new drugs from bench to bedside. These efforts include: synthesis, characterisation and formulation of a particular new Niclosamide Stearate Pro-drug Therapeutic (NSPT); NSPT testing in vitro for cell-uptake and cytotoxicity in glioblastoma, breast and prostate cancers; and in vivo preclinical studies in brain cancer. The “Bricks-to-Rocks” technology also extends to PET-imageable nanoparticles which, in combination with the NSPTs, form a suite of diagnostic and therapeutic (Diapeutic) "Individualised nano-medicines" for cancer.
Existing collaborations relevant to drug delivery
At Duke with the Eward Lab and Suter in NC State veterinary College, we have shown encouraging results in metastatic tumours in both preclinical mice and clinical canines with growth delays and extended lifetimes for the NSPT-treated animals. In new collaborations with David Walker, Ruman Rahman and Tracey Bradshaw in the CBTRC Nottingham, we are exploring the design, fabrication and testing of administration-route-specific formulations of brain tumor drugs for intra-venous-arterial, intrathecal and interstitial administration. Initial studies with the Rahman lab have demonstrated the potential for LDL-sized nanoparticles to access and be taken up by brain cancer cells in the perivascular space of tumors.
Publications relevant to drug delivery
Reddy, G. B., D. L. Kerr, I. Spasojevic, A. Tovmasyan, D. S. Hsu, B. E. Brigman, J. A. Somarelli, D. Needham and W. C. Eward (2020). "Preclinical Testing of a Novel Niclosamide Stearate Prodrug Therapeutic (NSPT) Shows Efficacy Against Osteosarcoma." Molecular Cancer Therapeutics 19(7):1448
D. Needham, (2020), Development of clinically effective formulations: why it is so difficult? (Ch 22), in: Biomaterials for cancer therapeutics: diagnosis, prevention and therapy, Pages 599-723,K. Park (ed.). Elsevier
Pablo Hervella, Johan Hygum Dam, Helge Thisgaard, Poul-Flemming Høilund-Carlsen, David Needham (2018) Chelation, formulation, encapsulation, retention, and in vivo biodistribution of hydrophobic nanoparticles labelled with 57Co-porphyrin: Oleylamine ensures stable chelation of cobalt in nanoparticles that accumulate in tumors. Journal of Controlled Release, 2018. 291: p. 11-25 doi: 10.1016/j.jconrel.2018.09.027
Hervella P, Parra-Ortiz E, Needham D (2016). Encapsulation and retention of chelated-copper inside hydrophobic nanoparticles: Liquid cored nanoparticles show better retention than a solid core forumation. European Journal of Pharmaceutics and Biopharmaceutics, 2016, 102, 64-76.
Needham D, Arslanagic A, Glud K, Hervella P, Karimi L, Høilund-Carlsen PF, Kinoshita K, Mollenhauer J, Parra E, Utoft A, Walke P (2016). Bottom Up Design of Nanoparticles (to eventually treat cancer): “Put the drug in the Cancer’s food”, in review, a “Special issue of J. Drug Targeting in honour of Pieter Cullis, Life-time Achievement Award for 2016” 24(9), 836-856.
Needham D (2016) “Bringing Research to Clinical Application: Lessons from Thermodox - A Thermal Sensitive Liposome for Treatment of Cancer”, invited chapter, In " Drug Delivery and Targeting: Fundamentals, Applications and Future Directions” Editors, HILLERY, AM, SWARBRICK J, PARK, K, CRC Press, Boca Raton, 523-583.
Manzoor AA, Lindner LH, Landon CD, Park JY, Simnick AJ, Dreher MR, Das S, Hanna G, Park W, Koning GA, ten Hagen TL, Needham D, Dewhirst MW (2012). Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors, Cancer Research 2012 Nov 1;72(21):5566-5575.
Needham D, Dewhirst MW (2012) Materials Science and Engineering of the Low Temperature Sensitive Liposome (LTSL): Composition-Structure-Property Relationships that Underlie its Design and Performance, (Chapter 2). In “Smart Materials for Drug Delivery”, Carmen Alvarez-Lorenzo and Angel Concheiro Eds, Royal Society of Chemistry, Publishing.
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