title: Biodegradable click capsules with engineered drug-loaded multilayers.
abstract: We report the modular assembly of a polymer-drug conjugate into covalently stabilized, responsive, biodegradable, and drug-loaded capsules with control over drug dose and position in the multilayer film. The cancer therapeutic, doxorubicin hydrochloride (DOX), was conjugated to alkyne-functionalized poly(l-glutamic acid) (PGA(Alk)) via amide bond formation. PGA(Alk) and PGA(Alk+DOX) were assembled via hydrogen bonding with poly(N-vinyl pyrrolidone) (PVPON) on planar and colloidal silica templates. The films were subsequently covalently stabilized using diazide cross-linkers, and PVPON was released from the multilayers by altering the solution pH to disrupt hydrogen bonding. After removal of the sacrificial template, single-component PGA(Alk) capsules were obtained and analyzed by optical microscopy, transmission electron microscopy, and atomic force microscopy. The PGA(Alk) capsules were stable in the pH range between 2 and 11 and exhibited reversible swelling/shrinking behavior. PGA(Alk+DOX) was assembled to form drug-loaded polymer capsules with control over drug dose and position in the multilayer system (e.g., DOX in every layer or exclusively in layer 3). The drug-loaded capsules could be degraded enzymatically, resulting in the sustained release of active DOX over approximately 2 h. Cellular uptake studies demonstrate that the viability of cells incubated with DOX-loaded PGA(Alk) capsules significantly decreased. The general applicability of this modular approach, in terms of incorporation of polymer-drug conjugates in other click multilayer systems, was also demonstrated. Biodegradable click capsules with drug-loaded multilayers are promising candidates as carrier systems for biomedical applications.
authors.affiliation: Centre for Nanoscience and Nanotechnology, Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ochs
authors.forename: Georgina K
authors.initials: GK
authors.lastname: Such
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Martin P
authors.initials: MP
authors.lastname: van Koeverden
authors.forename: Frank
authors.initials: F
authors.lastname: Caruso
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004738:Engineering / Q000379:methods*; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D049329:Nanostructures; D010316:Particle Size; D011099:Polyglutamic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D011108:Polymers; D011099:Polyglutamic Acid; D012822:Silicon Dioxide; D004317:Doxorubicin; D011205:Povidone