Encapsulation of conventional or genetic drugs in liposomal nanoparticles (LNP) can dramatically improve their pharmacological activity by altering their pharmacokinetics and biodistribution drugs and/or by acting as drug reservoirs allowing protection and sustained release of the therapeutic. Alterations in the biodistribution of liposomal encapsulated drugs occurs through a mechanism known as the enhanced permeability and retention (EPR) effect or passive targeting. Certain pathological conditions, such as inflammation or solid tumour growth, are associated with an increased permeability of the tissue vasculature which allows small particulate delivery systems, normally excluded from the tissues, to extravasate and accumulate at the site of disease.
In order for LN to effectively target tumour sites they must be small (~100nm), long circulating and either have a net neutral surface charge, or contain a polyethylene glycol (PEG) coating which acts as a shield, preventing plasma proteins from binding to the liposome and promoting rapid clearance.
In recognition of the fact that the development of drugs with proven clinical utility cannot be achieved solely within the academic environment due to the large capital investments required, Dr. Pieter Cullis has also been extensively involved in founding companies to commercialize technologies developed, at least in part, in his UBC laboratory. In all, these efforts have led to 10 drugs that have been approved or are in clinical or preclinical testing (see Table below). A large part of his professional life has involved the development of drugs to the point where they are of interest to the commercial world. This has led him to co-found the Centre for Drug Research and Development (www.cdrd.ca), which is aimed at developing, within academia, the extensive proof-of-concept data packages necessary to attract investment to preclinical drug candidates.
Drug |
Trade name |
Indication |
Status (2013) |
Company |
LNP Amphotericin |
ABELCET |
Fungal infections |
Approved US, Europe 1995 |
Enzon |
LNP Doxorubicin |
Myocet |
Metastatic breast cancer |
Approved Europe , Canada 2000 |
Cephalon |
LNP Vincristine |
Marqibo |
Acute lymphocytic leukemia, non-Hodgkin's lymphoma |
Approved US 2012 |
Talon |
LNP Vinorelbine |
Alocrest |
Breast cancer, non small cell lung cancer |
Phase I |
Talon |
LNP Topotecan |
Brakiva |
Ovarian cancer, small cell lung cancer |
Phase I |
Talon |
LNP siRNA PLK1 |
TKM-PLK1 |
Liver Cancer |
Phase I |
Tekmira |
LNP Ciprofloxacin |
|
Cystic fibrosis, Bronchiectasis, bioterrorism |
Phase II |
Aradigm |
LNP siRNA PCSK9 |
ALN-PCS |
Hypercholesterolemia |
Phase I |
Alnylam |
LNP siRNA VEGF-KSP |
ALN-VSP |
Primary and secondary liver cancer |
Phase I |
Alnylam |
LNP siRNA TTR |
ALN-TTR02 |
TTR-mediated amyloidosis |
Phase II |
Alnylam |