Systems - Research - Nanomedicine Research Group

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LNP Delivery Systems

LNP Improve the Pharmacological Activity of Encapsulated Drugs

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.

 

Clinical Applications of LNP Delivery Systems Developed in Our Lab

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.

 

Drugs Developed/Co-developed at UBC

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

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