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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| Format: | Article |
| Language: | English |
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MDPI AG
2019-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/4/723 |
| _version_ | 1817978841011847168 |
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| author | Tomasz Urbaniak Daniela Machová Olga Janoušková Witold Musiał |
| author_facet | Tomasz Urbaniak Daniela Machová Olga Janoušková Witold Musiał |
| author_sort | Tomasz Urbaniak |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T22:34:30Z |
| format | Article |
| id | doaj.art-a166a48206ee49cd8927aaba922f481b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T22:34:30Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a166a48206ee49cd8927aaba922f481b2022-12-22T02:26:48ZengMDPI AGMolecules1420-30492019-02-0124472310.3390/molecules24040723molecules24040723Microparticles of Lamivudine—Poly-ε-Caprolactone Conjugate for Drug Delivery via Internalization by MacrophagesTomasz Urbaniak0Daniela Machová1Olga Janoušková2Witold Musiał3Department of Physical Chemistry, Pharmaceutical Faculty, Wroclaw Medical University, Borowska 211, Wroclaw 50-556, PolandInstitute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovsky Sq. 2, 162 06 Prague 6, Czech RepublicInstitute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovsky Sq. 2, 162 06 Prague 6, Czech RepublicDepartment of Physical Chemistry, Pharmaceutical Faculty, Wroclaw Medical University, Borowska 211, Wroclaw 50-556, PolandThe 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.https://www.mdpi.com/1420-3049/24/4/723targeted drug deliverydrug-polymer conjugatesmicroparticlesdrug delivery via phagocytosislamivudinepoly-ε-caprolactone |
| spellingShingle | Tomasz Urbaniak Daniela Machová Olga Janoušková Witold Musiał Microparticles of Lamivudine—Poly-ε-Caprolactone Conjugate for Drug Delivery via Internalization by Macrophages Molecules targeted drug delivery drug-polymer conjugates microparticles drug delivery via phagocytosis lamivudine poly-ε-caprolactone |
| 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 | targeted drug delivery drug-polymer conjugates microparticles drug delivery via phagocytosis lamivudine poly-ε-caprolactone |
| url | https://www.mdpi.com/1420-3049/24/4/723 |
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