title: Dual-Cross-Linked Methacrylated Alginate Sub-Microspheres for Intracellular Chemotherapeutic Delivery.
abstract: Intracellular delivery vehicles comprised of methacrylated alginate (Alg-MA) were developed for the internalization and release of doxorubicin hydrochloride (DOX). Alg-MA was synthesized via an anhydrous reaction, and a mixture of Alg-MA and DOX was formed into sub-microspheres using a water/oil emulsion. Covalently cross-linked sub-microspheres were formed via exposure to green light, in order to investigate effects of cross-linking on drug release and cell internalization, compared to traditional techniques, such as ultraviolet (UV) light irradiation. Cross-linking was performed using light exposure alone or in combination with ionic cross-linking using calcium chloride (CaCl2). Alg-MA sub-microsphere diameters were between 88 and 617 nm, and ζ-potentials were between -20 and -37 mV. Using human lung epithelial carcinoma cells (A549) as a model, cellular internalization was confirmed using flow cytometry; different sub-microsphere formulations varied the efficiency of internalization, with UV-cross-linked sub-microspheres achieving the highest internalization percentages. While blank (nonloaded) Alg-MA submicrospheres were noncytotoxic to A549 cells, DOX-loaded sub-microspheres significantly reduced mitochondrial activity after 5 days of culture. Photo-cross-linked Alg-MA sub-microspheres may be a potential chemotherapeutic delivery system for cancer treatment.
authors.affiliation: Bioengineering Program, College of Engineering and Mathematical Sciences, College of Medicine, University of Vermont, Burlington VT 05405.
authors.forename: Spencer L
authors.initials: SL
authors.lastname: Fenn
authors.affiliation: Bioengineering Program, College of Engineering and Mathematical Sciences, College of Medicine, University of Vermont, Burlington VT 05405.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Miao
authors.affiliation: Department of Microbiology and Molecular Genetics, College of Medicine, University of Vermont Burlington, VT 05405.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Scherrer
authors.affiliation: Bioengineering Program, College of Engineering and Mathematical Sciences, College of Medicine, University of Vermont, Burlington VT 05405.|Mechanical Engineering Program, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT 05405.|Department of Orthopaedics and Rehabilitation, College of Medicine, University of Vermont, Burlington, VT 05405.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Floreani
mesh_terms: D000072283:A549 Cells; D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008863:Microspheres
chemical_list: D000464:Alginates; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008689:Methacrylates; D004317:Doxorubicin
keywords: alginate; cancer; drug delivery; intracellular; methacrylation; visible-light cross-linking