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Microparticles of Lamivudine—Poly-ε-Caprolactone Conjugate for Drug Delivery via Internalization by Macrophages

The past decade may be considered as revolutionary in the research field focused on the physiological function of macrophages. Unknown subtypes of these cells involved in pathological mechanisms were described recently, and they are considered as potential drug delivery targets. The innate ability t...

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Autores principales: Urbaniak, Tomasz, Machová, Daniela, Janoušková, Olga, Musiał, Witold
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413034/
https://www.ncbi.nlm.nih.gov/pubmed/30781578
http://dx.doi.org/10.3390/molecules24040723
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author Urbaniak, Tomasz
Machová, Daniela
Janoušková, Olga
Musiał, Witold
author_facet Urbaniak, Tomasz
Machová, Daniela
Janoušková, Olga
Musiał, Witold
author_sort Urbaniak, Tomasz
collection PubMed
description The past decade may be considered as revolutionary in the research field focused on the physiological function of macrophages. Unknown subtypes of these cells involved in pathological mechanisms were described recently, and they are considered as potential drug delivery targets. The innate ability to internalize foreign bodies exhibited by macrophages can be employed as a therapeutic strategy. The efficiency of this uptake depends on the size, shape and surface physiochemical properties of the phagocyted objects. Here, we propose a method of preparation and preliminary evaluation of drug-polymer conjugate-based microspheres for macrophage targeted drug delivery. The aim of the study was to identify crucial uptake-enhancing parameters for solid, surface modified particles. A model drug molecule—lamivudine—was conjugated with poly-ε-caprolactone via ring opening polymerization. The conjugate was utilized in a solvent evaporation method technique to form solid particles. Interactions between particles and a model rat alveolar cell line were evaluated by flow cytometry. The polymerization product was characterized by a molecular weight of 3.8 kDa. The surface of the obtained solid drug-loaded cores of a hydrodynamic diameter equal to 2.4 µm was modified with biocompatible polyelectrolytes via a layer-by-layer assembly method. Differences in the internalization efficiency of four particle batches by the model RAW 264.7 cell line suggest that particle diameter and surface hydrophobicity are the most influential parameters in terms of phagocytic uptake.
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spelling pubmed-64130342019-04-09 Microparticles of Lamivudine—Poly-ε-Caprolactone Conjugate for Drug Delivery via Internalization by Macrophages Urbaniak, Tomasz Machová, Daniela Janoušková, Olga Musiał, Witold Molecules Article The past decade may be considered as revolutionary in the research field focused on the physiological function of macrophages. Unknown subtypes of these cells involved in pathological mechanisms were described recently, and they are considered as potential drug delivery targets. The innate ability to internalize foreign bodies exhibited by macrophages can be employed as a therapeutic strategy. The efficiency of this uptake depends on the size, shape and surface physiochemical properties of the phagocyted objects. Here, we propose a method of preparation and preliminary evaluation of drug-polymer conjugate-based microspheres for macrophage targeted drug delivery. The aim of the study was to identify crucial uptake-enhancing parameters for solid, surface modified particles. A model drug molecule—lamivudine—was conjugated with poly-ε-caprolactone via ring opening polymerization. The conjugate was utilized in a solvent evaporation method technique to form solid particles. Interactions between particles and a model rat alveolar cell line were evaluated by flow cytometry. The polymerization product was characterized by a molecular weight of 3.8 kDa. The surface of the obtained solid drug-loaded cores of a hydrodynamic diameter equal to 2.4 µm was modified with biocompatible polyelectrolytes via a layer-by-layer assembly method. Differences in the internalization efficiency of four particle batches by the model RAW 264.7 cell line suggest that particle diameter and surface hydrophobicity are the most influential parameters in terms of phagocytic uptake. MDPI 2019-02-17 /pmc/articles/PMC6413034/ /pubmed/30781578 http://dx.doi.org/10.3390/molecules24040723 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Urbaniak, Tomasz
Machová, Daniela
Janoušková, Olga
Musiał, Witold
Microparticles of Lamivudine—Poly-ε-Caprolactone Conjugate for Drug Delivery via Internalization by Macrophages
title Microparticles of Lamivudine—Poly-ε-Caprolactone Conjugate for Drug Delivery via Internalization by Macrophages
title_full Microparticles of Lamivudine—Poly-ε-Caprolactone Conjugate for Drug Delivery via Internalization by Macrophages
title_fullStr Microparticles of Lamivudine—Poly-ε-Caprolactone Conjugate for Drug Delivery via Internalization by Macrophages
title_full_unstemmed Microparticles of Lamivudine—Poly-ε-Caprolactone Conjugate for Drug Delivery via Internalization by Macrophages
title_short Microparticles of Lamivudine—Poly-ε-Caprolactone Conjugate for Drug Delivery via Internalization by Macrophages
title_sort microparticles of lamivudine—poly-ε-caprolactone conjugate for drug delivery via internalization by macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413034/
https://www.ncbi.nlm.nih.gov/pubmed/30781578
http://dx.doi.org/10.3390/molecules24040723
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