title: Innovative use of the taxol binding peptide overcomes key challenges of stable and high drug loading in polymeric nanomicelles.
abstract: Despite widespread clinical use, delivery of taxane chemotherapeutics remains a challenge due to poor solubility and lack of selectively. Polymeric nanomicelle strategies have been pursued to overcome these issues; however current formulations are often limited by low drug loading and poor serum stability. To achieve a drug delivery system that addresses these issues, poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-g-poly(ethylene glycol) was covalently modified with the taxol binding peptide – a peptide from the β-tubulin-taxane binding site. This modification resulted in drug loadings five times higher than unmodified polymers, which is significantly higher than typical hydrophobic modifications, including with benzyl and docetaxel functionalization. Unlike many formulations with high drug loading, these nanomicelles were stable in serum for up to 24 h and maintained docetaxel cytotoxicity. By incorporating the taxane binding peptide into the polymer chemistry, a new twist was applied to an old problem, which is broadly applicable to other polymeric micelle systems and drug-peptide combinations in general.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 160 College St, Toronto, ON M5S3E1, Canada. molly.shoichet@utoronto.ca.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Logie
authors.forename: Christopher K
authors.initials: CK
authors.lastname: McLaughlin
authors.forename: Roger Y
authors.initials: RY
authors.lastname: Tam
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001665:Binding Sites; D001952:Bridged-Ring Compounds / Q000378:metabolism; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D008823:Micelles; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; D043823:Taxoids; D000077143:Docetaxel; C080625:taxane; D011092:Polyethylene Glycols; D017239:Paclitaxel