title: Ultrasonically Assisted Polysaccharide Microcontainers for Delivery of Lipophilic Antitumor Drugs: Preparation and in Vitro Evaluation.
abstract: High toxicity, poor selectivity, and severe side effects are major drawbacks of anticancer drugs. Various drug delivery systems could be proposed to overcome these limitations. The aim of this study was to fabricate polysaccharide microcontainers (MCs) loaded with thymoquinone (TQ) by a one-step ultrasonication technique and to study their cellular uptake and cytotoxicity in vitro. Two MC fractions with a mean size of 500 nm (MC-0.5) and 2 μM (MC-2) were prepared and characterized. Uptake of the MCs by mouse melanoma M-3 cells was evaluated in both 2D (monolayer culture) and 3D (multicellular tumor spheroids) models by confocal microscopy, flow cytometry, and fluorimetry. The higher cytotoxicity of the TQ-MC-0.5 sample than the TQ-MC-2 fraction was in good correlation with higher MC-0.5 accumulation in the cells. The MC-0.5 beads were more promising than the MC-2 particles because of a higher cellular uptake in both 2D and 3D models, an enhanced antitumor effect, and a lower nonspecific toxicity.
authors.affiliation: †Polymers for Biology Laboratory, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Miklukho-Maklaya 16/10, Moscow, Russia.|‡Laboratory of Bioorganic Structures, Shubnikov Institute of Crystallography of the Russian Academy of Sciences, 119333, Leninskii Prospekt 59, Moscow, Russia.
authors.forename: Roman
authors.initials: R
authors.lastname: Akasov
authors.affiliation: ‡Laboratory of Bioorganic Structures, Shubnikov Institute of Crystallography of the Russian Academy of Sciences, 119333, Leninskii Prospekt 59, Moscow, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Borodina
authors.affiliation: †Polymers for Biology Laboratory, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Miklukho-Maklaya 16/10, Moscow, Russia.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Zaytseva
authors.affiliation: †Polymers for Biology Laboratory, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Miklukho-Maklaya 16/10, Moscow, Russia.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Sumina
authors.affiliation: ‡Laboratory of Bioorganic Structures, Shubnikov Institute of Crystallography of the Russian Academy of Sciences, 119333, Leninskii Prospekt 59, Moscow, Russia.|§National Research Centre, Kurchatov Institute, 123182, Akademika Kurchatova Ploshchad 1, Moscow, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Bukreeva
authors.affiliation: ∥Synthesis of Peptides and Polymer Microspheres Laboratory, Institute of Macromolecular Compounds of the Russian Academy of Sciences, 199004, Bolshoy Prospekt 31, Saint-Petersburg, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Burov
authors.affiliation: †Polymers for Biology Laboratory, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Miklukho-Maklaya 16/10, Moscow, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Markvicheva
mesh_terms: D065966:Absorption, Physicochemical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002214:Capsules / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004058:Diffusion / Q000528:radiation effects; D053672:Electrochemotherapy / Q000379:methods*; D008055:Lipids / Q000737:chemistry; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D011134:Polysaccharides / Q000737:chemistry*; D013010:Sonication / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D008055:Lipids; D011134:Polysaccharides
keywords: chitosan; drug delivery systems; microcontainers; multicellular tumor spheroids; ultrasonication; xanthan gum