title: Amphiphilic micelles of poly(2-methyl-2-carboxytrimethylene carbonate-co-D,L-lactide)-graft-poly(ethylene glycol) for anti-cancer drug delivery to solid tumours.
abstract: Drug delivery to solid tumours remains a challenge because both tumour physiology and drug solubility are unfavourable. Engineered materials can provide the basis for drug reformulation, incorporating active compounds and modulating their pharmacokinetic and biodistribution behaviour. To this end, we encapsulated docetaxel, a poorly soluble taxane drug, in a self-assembled polymeric nanoparticle micelle of poly(2-methyl-2-carboxytrimethylene carbonate-co-D,L-lactide)-graft-poly(ethylene glycol) (poly(TMCC-co-LA)-g-PEG). This formulation was compared with its conventional ethanolic polysorbate 80 formulation in terms of plasma circulation and biodistribution in an orthotopic mouse model of breast cancer. Notably, the polymeric nanoparticle formulation achieved greater tumour retention, resulting in prolonged exposure of cancer cells to the active drug. This behaviour was unique to the tumour tissue. The active drug was eliminated at equal or greater rates in all other tissues assayed when delivered in the polymeric nanoparticles vs. the free drug formulation. Thus, these polymeric nanoparticles are promising vehicles for solid tumour drug delivery applications, offering greater tumour exposure while eliminating the need for toxic solvents and surfactants in the dosing formulation.
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, Department of Chemical Engineering & Applied Chemistry, Institute of Biomaterials & Biomedical Engineering, University of Toronto, Room 514, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors.forename: Karyn S
authors.initials: KS
authors.lastname: Ho
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Aman
authors.forename: Rima S
authors.initials: RS
authors.lastname: Al-awar
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D002254:Carbonates / Q000737:chemistry* / Q000378:metabolism; D004146:Dioxanes / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D008422:Materials Testing; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008823:Micelles; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D002254:Carbonates; D004146:Dioxanes; D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; C091880:dilactide