Delivery of biologics to select organelles--the role of biologically active polymers.

ABSTRACT

Biologics (i.e., nucleic acid and protein-based drugs) suffer from poor bioavailability, as membrane partitioning and intracellular targeting are a significant problem. Various strategies have been developed in an attempt to modulate biologics bioavailability by means of manipulating whole body pharmacokinetics and subcellular trafficking. Limited direct success has been observed. This review focuses on the components of nanomedicine systems rather than the whole, facilitating an overview of materials that may be of clinical relevance in the future. Some of the advantages and disadvantages associated with the use of soluble drug delivery systems are considered. Although the focus is on linear poly(amidoamine) polymers, emerging technologies capable of the delivery of large molecules to other specific intracellular compartments are also examined. The focus is maintained on cytosolic access for two reasons, initially because this intracellular compartment may be viewed as a 'gateway' to other intracellular organelles and also because this is where the greatest therapeutic benefit is likely to be found. It is likely that in the coming years and in combination with other existing, well-characterized drug delivery platform technologies, such as liposomal formulation or polymer conjugation, that the targeting of specific organelles will become more accessible.