• Polymer-based drug delivery systems for controlled and localized drug delivery
• Synthesis and evaluation of new biodegradable polymers as biomaterials or carriers for drugs
• Amphiphilic copolymers as inhibitors of drug efflux transporters
• Solid state pharmaceutics
• Crystal-induced inflammatory arthritis: signaling pathways leading to neutrophil activation
  

Title: Angiotech Professor of Drug Delivery, Associate Dean of Research and Graduate Studies

Email: burt@interchange.ubc.ca

Telephone: 604-822-2440

Fax: 604-822-3035

Trainees: Kevin Letchford, Clement Mugabe, Chris Springate, Chiming Yang

Links: Burt Lab Website

Degrees:

 

Research Focus:

My research efforts are focused in two major areas. Through collaborations with many different groups, we have developed controlled release and targeted polymeric delivery systems for paclitaxel and other drugs. Novel biodegradable polymers have been synthesized and used in applications such as intravenous, perivascular, intratumoral, and intra-articular drug delivery. We also investigate the mechanisms by which inflammatory crystals deposited in synovial joints activate neutrophils and delay apoptosis in crystal-induced inflammatory arthritis.

Current Projects:

Polymeric drug delivery systems. Our group has developed a large number of different delivery systems for various applications. Examples include the following: diblock copolymer micellar delivery system for paclitaxel, injectable intratumoral pastes based on triblock copolymers, intra-articular and intra-peritoneal microspheres, implantable films for perivascular application and for prevention of postsurgical adhesions. On-going research is exploring interactions of micellar and nanoparticulate delivery systems with blood components and tissues. Inhibition of drug efflux transporters by amphiphilic diblock copolymers. It is not possible to administer a large number of drugs, such as paclitaxel, by the oral route because of very poor absorption in the intestine. P-glycoprotein (Pgp), a multi-drug transporter protein located in the cell membranes of cells lining the intestine, actively pumps paclitaxel out of the cells and back into the intestinal lumen. We determined that some diblock copolymers dramatically increase paclitaxel uptake by model intestinal (caco-2) cells. We believe the mechanism involves modulation of the cell membrane and subsequent inhibition of Pgp activity. We are investigating the properties of the copolymers necessary for the drug accumulation effect and the mechanisms and role of multi-drug transporter proteins in this process. (Funding: Canadian Institutes of Health Research Operating Grant) Mesenchymal stem cells and biomaterial in bone regeneration. We are part of a multidisciplinary team investigating the development of a multicomponent composite for use in revision hip surgery. Our group is exploring the use of polymer scaffolds for stem cells and growth factor delivery. (Funding: Canadian Institutes of Health Research New Emerging Team Grant) Paclitaxel-loaded microspheres targeted to angiogenic zones of prostate tumors. Paclitaxel-loaded microspheres, surface-modified with antibodies to growth factors found preferentially on growing capillaries in tumors are being developed. (Funding: Canadian Prostate Cancer Research Initiative) Crystal-induced neutrophil activation in arthritis. In crystal-induced arthritis, monosodium urate monohydrate crystals and calcium pyrophosphate dihydrate crystals that form in the synovial joint fluid interact with neutrophils leading to an oxidative burst, engulfment of the crystals and the release of proteolytic enzymes. We have determined that the crystals also delay neutrophil apoptosis, promoting the accumulation of these cells in the joints, and an extended inflammatory response. We are investigating both the mechanism by which crystals activate neutrophils and delay normal apoptosis. We hope to identify neutrophil signaling pathways and understand how the inflammatory response is regulated by factors such as neutrophil apoptosis. (Funding: Canadian Institutes of Health Research Operating Grant)

Selected Publications:

Letchford, K. and Burt, H.M. "A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersome", Eur. J. Pharm. Biopharm. In Press (2006). Yang C., Burt H.M. "Drug-eluting stents: factors governing local pharmacokinetics", Adv. Drug Deliv. Rev. 58(3): 402-11 (2006). PubMed Zastre J., Jackson J.K., Wong W., Burt H.M. "Methoxypolyethylene glycol-block-polycaprolactone diblock copolymers reduce P-glycoprotein efflux in the absence of a membrane fluidization effect while stimulating P-glycoprotein ATPase activity", J. Pharm. Sci. In Press (2006) PubMed Liang L.S., Wong W., Burt H.M. "Pharmacokinetic study of methotrexate following intra-articular injection of methotrexate loaded poly(L-lactic acid) microspheres in rabbits", J. Pharm. Sci. 94(6): 1204-15 (2005). PubMed Springate C.M., Jackson J.K., Gleave M.E., Burt H.M. "Efficacy of an intratumoral controlled release formulation of clusterin antisense oligonucleotide complexed with chitosan containing paclitaxel or docetaxel in prostate cancer xenograft models", Cancer Chemother. Pharmacol. 56(3): 239-47 (2005). PubMed Zastre J., Jackson J., Burt H. "Evidence for modulation of P-glycoprotein-mediated efflux by methoxypolyethylene glycol-block-Polycaprolactone amphiphilic diblock copolymers." Pharm Res. 21(8):1489-97 (2004). PubMed