title: Poly(amidoamine) polymers: soluble linear amphiphilic drug-delivery systems for genes, proteins and oligonucleotides.
abstract: Polymer-drug and polymer-protein conjugates are emerging as a robust and well-characterized class of therapeutic entity. Although there are no low-molecular-weight soluble polymer conjugates in routine clinical use, there are many examples of routinely used high-molecular-weight drugs conjugated to soluble polymers (e.g., Oncospar). Advances in synthetic polymer chemistry have fostered the development of linear poly(amidoamine)s (PAA)s that impart both biodegradability, 'smart' (pH responsive) biological activity and biocompatibility. In their linear form, such as hyper-branched poly(amidoamine) (PAMAM) dendrimers, linear PAAs can be used to deliver large therapeutic entities such as peptides, proteins and genes to either the cytosol or nucleus. Furthermore, these polymers offer great potential in vivo due to their ability to either target the liver or be directed away from the liver and enter tumor mass via the enhanced permeability and retention (EPR) effect. PAAs also exhibit minimal toxicity (dependent upon backbone chemistry), relative to well-characterized polymers used for gene delivery. The propensity of PAAs to modulate intracellular trafficking resulting in their cytosolic translocation has also recently been quantified in vivo and is the primary focus of this article.
authors: School of Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.
authors: Marie W
authors: MW
authors: Pettit
authors: Peter
authors: P
authors: Griffiths
authors: Paolo
authors: P
authors: Ferruti
authors: Simon C W
authors: SC
authors: Richardson
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism; D050091:Dendrimers / Q000009:adverse effects / Q000737:chemistry; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D006801:Humans; D009841:Oligonucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics; D011073:Polyamines / Q000009:adverse effects / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D009841:Oligonucleotides; C104700:PAMAM Starburst; C531249:Poly(amidoamine); D011073:Polyamines; D011506:Proteins