Development of mucoadhesive 3D-printed Carbopol/Eudragit/SNAC tablets for the oral delivery of enoxaparin: In vitro and ex vivo evaluation

被引:0
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作者
Chatzitaki, Aikaterini-Theodora [1 ,2 ]
Patila, Michaela [3 ]
Stamatis, Haralampos [3 ]
Vizirianakis, Ioannis S. [4 ,5 ]
Rekka, Eleni A. [6 ]
Tzetzis, Dimitrios [7 ]
Spyros, Apostolos [8 ]
Zacharis, Constantinos K. [9 ]
Ritzoulis, Christos [10 ]
Fatouros, Dimitrios G. [1 ,2 ]
机构
[1] Aristotle Univ Thessaloniki, Sch Pharm, Dept Pharmaceut Technol, GR-54124 Thessaloniki, Greece
[2] Ctr Interdisciplinary Res & Innovat CIRI AUTH, Thessaloniki, Greece
[3] Univ Ioannina, Dept Biol Applicat & Technol, Lab Biotechnol, Ioannina 45110, Greece
[4] Aristotle Univ Thessaloniki, Fac Hlth Sci, Sch Pharm, Lab Pharmacol, GR-54124 Thessaloniki, Greece
[5] Univ Nicosia, Sch Life & Hlth Sci, Dept Hlth Sci, Nicosia, Cyprus
[6] Aristotelian Univ Thessaloniki, Sch Pharm, Dept Pharmaceut Chem, Thessaloniki 54124, Greece
[7] Int Hellen Univ, Sch Sci & Technol, Digital Mfg & Mat Characterizat Lab, Thermi 57001, Greece
[8] Univ Crete, Dept Chem, NMR Lab, Voutes Campus,Box 2208, GR-71003 Iraklion, Greece
[9] Aristotle Univ Thessaloniki, Dept Pharm, Lab Pharmaceut Anal, GR-54124 Thessaloniki, Greece
[10] Int Hellen Univ, Dept Food Sci & Technol, Thessaloniki, Greece
关键词
3D printing; Oral delivery; Enoxaparin; SNAC; Ex vivo permeability; Cytotoxicity; MOLECULAR-WEIGHT HEPARINS; CIRCULAR-DICHROISM; STRUCTURAL DIFFERENTIATION; ABSORPTION; ENHANCEMENT; MECHANISM; SODIUM; ACID;
D O I
10.1016/j.ijpharm.2024.124627
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
3D-printed dosage forms comprised of Carbopol and Eudragit were fabricated through semi-solid extrusion, combining Enoxaparin (Enox) and the permeation enhancer SNAC in a single-step process without subsequent post-processing. Inks were characterized using rheology and Fourier-transform infrared (FTIR) spectroscopy. The stability of Enox in the fabricated dosage forms was assessed by means of Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) analysis. In vitro release studies revealed the release of Enox in a sustained manner, whereas ex vivo experiments demonstrated the mucoadhesive properties of the 3D-printed dosage forms and their ability to enhance Enox permeability across intestinal mucosa. Cellular assays (CCK-8 assay) revealed a dose- and time-dependent response following incubation with the 3D-printed dosage forms. The encapsulation of SNAC in the 3D-printed dosage forms demonstrated their capacity to increase the transcellularly transport of macromolecule across Caco-2 monolayer in a reversible manner, as confirmed by Transepithelial Resistance (TEER) measurements.
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页数:11
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