title: Cyclodextrin-based star polymers as a versatile platform for nanochemotherapeutics: Enhanced entrapment and uptake of idarubicin.
abstract: A series of cyclodextrin-based star polymers were synthesized using β-cyclodextrin (CD) as hydrophilic core, methyl methacrylate (MMA) and tert-butyl acrylate (tBA) as hydrophobic arms. Star polymers, either homopolymers or random/block copolymers, showed narrow molecular weight distributions. Grafting hydrophobic arms created CD-based nanoparticles (CD-NPs) in the size range (130-200nm) with narrow PdI <0.15 and slightly negative ζ-potential. Particle surface could be modified with chitosan to impart a positive surface charge. Colloidal stability of CD-NPs was a function of pH as revealed by the pH-titration curves. CD-NPs were used as carrier for the chemotherapeutic drug idarubicin (encapsulation efficiency, EE ∼40%) ensuring prolonged release profile (∼80% after 48h). For cell-based studies, coumarin-6 was encapsulated as a fluorescent marker (EE ∼75%). Uptake studies carried out on A549 and Caco-2 cell lines proved the uptake of coumarin-loaded NPs as a function of time and preferential localization in the cytoplasm. Uptake kinetics revealed no saturation or plateau over 6h. Chitosan-modified NPs showed significantly improved, concentration-dependent cellular uptake. Meanwhile, CD-NPs were non-cytotoxic on both cell lines over the concentration range (0.25-3mg/ml) as studied by MTT and LDH assays. In conclusion, CD star polymers can be considered a versatile platform for a new class of biocompatible nanochemotherapy.
authors.affiliation: Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany; Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 21521 Alexandria, Egypt. Electronic address: noha.nafee@mx.uni-saarland.de.
authors.forename: N
authors.initials: N
authors.lastname: Nafee
authors.affiliation: Organic Macromolecular Chemistry, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hirosue
authors.affiliation: Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), 66123 Saarbrücken, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Loretz
authors.affiliation: Organic Macromolecular Chemistry, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wenz
authors.affiliation: Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany; Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), 66123 Saarbrücken, Germany.
authors.forename: C-M
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002482:Cellulose / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D003505:Cyclodextrins; D004337:Drug Carriers; C041953:cyclodextrin polymer; D011092:Polyethylene Glycols; D002482:Cellulose; D048271:Chitosan; D007770:L-Lactate Dehydrogenase; D015255:Idarubicin
keywords: Chemotherapy; Chitosan; Cyclodextrin; Idarubicin; Nanoparticles; Star copolymer