Abstract
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.
Highlights
During the last decades the field of micro and nano drug delivery systems has gained unprecedented attention due to possibility of therapy improvement on various levels.Numerous advancements, e.g., side effect abatement, improvement of therapy efficiency, theranostic systems and control of drug distribution after administration are examples of the goals achieved through the use of particle-based submicron systems [1]
Crucial particle features such as size, chemical composition, targeting ligand type are selected depending on the addressed cells, and multiple chemical, physical or biological factors are considered during targeted drug delivery system design [3]
Macrophages are often recognized as viral reservoirs, especially these located in sites hardly accessible to drug substances, so called “sanctuaries”, i.e., in the central nervous system [12]
Summary
During the last decades the field of micro and nano drug delivery systems has gained unprecedented attention due to possibility of therapy improvement on various levels.Numerous advancements, e.g., side effect abatement, improvement of therapy efficiency, theranostic systems and control of drug distribution after administration are examples of the goals achieved through the use of particle-based submicron systems [1]. Delivery based on interactions between particles and cell-specific ligands is referred as active targeting, while taking advantage of leaky intercellular junctions, i.e., in inflamed or cancerous tissues, is termed passive targeting [2]. Crucial particle features such as size, chemical composition, targeting ligand type are selected depending on the addressed cells, and multiple chemical, physical or biological factors are considered during targeted drug delivery system design [3]. The passive macrophage targeted drug delivery may exploit the ability of the cells to phagocyte foreign bodies, including microparticles [15]. In the case of macrophage targeted drug delivery, release from micro-matrices should be possibly postponed up to the onset of cellular uptake, for instance via conjugating a drug molecule with poorly hydrolyzable polyester chains like poly-ε-caprolactone (PCL). Numerous investigated variants of ROP systems include metallic catalysts and initiators containing hydroxyl or amine moieties [22]
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