In-House Innovative “Diamond Shaped” 3D Printed Microfluidic Devices for Lysozyme-Loaded Liposomes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Design and Manufacturing of 3DP Chips
2.3. Production of LPs by MFs
2.4. Physicochemical Characterization of LPs
2.5. Stability Studies
2.6. Encapsulation Efficacy and In Vitro Release Study
2.7. Statistical Analysis
3. Results and Discussion
3.1. Rationale behind the Design of MF Devices
3.2. Manufacturing of 3D DLP-Printed Devices
3.3. LPs’ Optimization and Production
3.4. Stability Studies
3.5. EE% and In Vitro Release Study
4. Conclusions and Future Perspectives
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Gonzalez-Valdivieso, J.; Girotti, A.; Schneider, J.; Arias, F.J. Advanced Nanomedicine and Cancer: Challenges and Opportunities in Clinical Translation. Int. J. Pharm. 2021, 599, 120438. [Google Scholar] [CrossRef] [PubMed]
- Kara, A.; Vassiliadou, A.; Ongoren, B.; Keeble, W.; Hing, R.; Lalatsa, A.; Serrano, D.R.; Parhizkar, M.; Tsaoulidis, D. Engineering 3D Printed Microfluidic Chips for the Fabrication of Nanomedicines. Pharmaceutics 2021, 13, 2134. [Google Scholar] [CrossRef] [PubMed]
- Arduino, I.; Iacobazzi, R.M.; Riganti, C.; Lopedota, A.A.; Perrone, M.G.; Lopalco, A.; Cutrignelli, A.; Cantore, M.; Laquintana, V.; Franco, M.; et al. Induced Expression of P-Gp and BCRP Transporters on Brain Endothelial Cells Using Transferrin Functionalized Nanostructured Lipid Carriers: A First Step of a Potential Strategy for the Treatment of Alzheimer’s Disease. Int. J. Pharm. 2020, 591, 120011. [Google Scholar] [CrossRef]
- Sommonte, F.; Arduino, I.; Racaniello, G.F.; Lopalco, A.; Lopedota, A.A.; Denora, N. The Complexity of the Blood-Brain Barrier and the Concept of Age-Related Brain Targeting: Challenges and Potential of Novel Solid Lipid-Based Formulations. J. Pharm. Sci. 2021, 111, 577–592. [Google Scholar] [CrossRef] [PubMed]
- Patra, J.K.; Das, G.; Fraceto, L.F.; Campos, E.V.R.; Rodriguez-Torres, M.D.P.; Acosta-Torres, L.S.; Diaz-Torres, L.A.; Grillo, R.; Swamy, M.K.; Sharma, S.; et al. Nano Based Drug Delivery Systems: Recent Developments and Future Prospects. J. Nanobiotechnol. 2018, 16, 71. [Google Scholar] [CrossRef] [Green Version]
- Iacobazzi, R.M.; Vischio, F.; Arduino, I.; Canepa, F.; Laquintana, V.; Notarnicola, M.; Scavo, M.P.; Bianco, G.; Fanizza, E.; Lopedota, A.A.; et al. Magnetic Implants in Vivo Guiding Sorafenib Liver Delivery by Superparamagnetic Solid Lipid Nanoparticles. J. Colloid. Interface Sci. 2022, 608, 239–254. [Google Scholar] [CrossRef] [PubMed]
- Pardi, N.; Hogan, M.J.; Porter, F.W.; Weissman, D. MRNA Vaccines-a New Era in Vaccinology. Nat. Rev. Drug Discov. 2018, 17, 261–279. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tian, T.; Jian, R.; Jia, Z.; Chun-Xia, Z.; Dong, C.; Jianzhen, S. Nanocarrier-Based Tumor-Targeting Drug Delivery Systems for Hepatocellular Carcinoma Treatments: Enhanced Therapeutic Efficacy and Reduced Drug Toxicity. J. Biomed. Nanotechnol. 2022, 18, 660–676. [Google Scholar] [CrossRef]
- Chung, Y.H.; Beiss, V.; Fiering, S.N.; Steinmetz, N.F. COVID-19 Vaccine Frontrunners and Their Nanotechnology Design. ACS Nano 2020, 14, 12522–12537. [Google Scholar] [CrossRef]
- Liu, P.; Chen, G.; Zhang, J. A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives. Molecules 2022, 27, 1372. [Google Scholar] [CrossRef]
- Mahmoud, K.; Swidan, S.; El-Nabarawi, M.; Teaima, M. Lipid Based Nanoparticles as a Novel Treatment Modality for Hepatocellular Carcinoma: A Comprehensive Review on Targeting and Recent Advances. J. Nanobiotechnol. 2022, 20, 109. [Google Scholar] [CrossRef] [PubMed]
- Böttger, R.; Pauli, G.; Chao, P.H.; al Fayez, N.; Hohenwarter, L.; Li, S.D. Lipid-Based Nanoparticle Technologies for Liver Targeting. Adv. Drug Deliv. Rev. 2020, 154–155, 79–101. [Google Scholar] [CrossRef] [PubMed]
- Mirzavi, F.; Barati, M.; Soleimani, A.; Vakili-Ghartavol, R.; Jaafari, M.R.; Soukhtanloo, M. A Review on Liposome-Based Therapeutic Approaches against Malignant Melanoma. Int. J. Pharm. 2021, 599, 12413. [Google Scholar] [CrossRef] [PubMed]
- Arduino, I.; Liu, Z.; Rahikkala, A.; Figueiredo, P.; Correia, A.; Cutrignelli, A.; Denora, N.; Santos, H.A. Preparation of Cetyl Palmitate-Based PEGylated Solid Lipid Nanoparticles by Microfluidic Technique. Acta Biomater. 2021, 121, 566–578. [Google Scholar] [CrossRef]
- Arduino, I.; Liu, Z.; Iacobazzi, R.M.; Lopedota, A.A.; Lopalco, A.; Cutrignelli, A.; Laquintana, V.; Porcelli, L.; Azzariti, A.; Franco, M.; et al. Microfluidic Preparation and in Vitro Evaluation of IRGD-Functionalized Solid Lipid Nanoparticles for Targeted Delivery of Paclitaxel to Tumor Cells. Int. J. Pharm. 2021, 610, 121246. [Google Scholar] [CrossRef]
- Iacobazzi, R.M.; Arduino, I.; di Fonte, R.; Lopedota, A.A.; Serratì, S.; Racaniello, G.; Bruno, V.; Laquintana, V.; Lee, B.C.; Silvestris, N.; et al. Microfluidic-Assisted Preparation of Targeted Ph-Responsive Polymeric Micelles Improves Gemcitabine Effectiveness in Pdac: In Vitro Insights. Cancers 2022, 14, 5. [Google Scholar] [CrossRef]
- Huang, L.; Su, E.; Liu, Y.; He, N.; Deng, Y.; Jen, L.; Chen, Z.; Li, S. A microfluidic device for accurate detection of hs-cTnI. Chin. Chem. Lett. 2021, 32, 1550–1558. [Google Scholar] [CrossRef]
- Jaradat, E.; Weaver, E.; Meziane, A.; Lamprou, D.A. Microfluidic paclitaxel-loaded nanoparticles formulation for chemotherapy. Int. J. Pharm. 2022, 628, 122320. [Google Scholar] [CrossRef]
- Doherty, M.; Wang, T.; Lamprou, D.A.; Coulter, J.A. Microfluidic Technologies in Tumour Metabolism. Int. J. Pharm. 2022, 629, 122370. [Google Scholar] [CrossRef]
- Weaver, E.; O’Hagan, C.; Lamprou, D.A. The Sustainability of Emerging Technologies for Use in Pharmaceutical Manufacturing. Expert Opin. Drug Deliv. 2022, 7, 861–872. [Google Scholar] [CrossRef]
- Nielsen, A.V.; Beauchamp, M.J.; Nordin, G.P.; Woolley, A.T. 3D Printed Microfluidics. Annu. Rev. Anal.Chem 2020, 13, 45–65. [Google Scholar] [CrossRef] [PubMed]
- Mathew, E.; Pitzanti, G.; Larrañeta, E.; Lamprou, D.A. Three-Dimensional Printing of Pharmaceuticals and Drug Delivery Devices. Pharmaceutics 2020, 12, 266. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, Y.; Zhou, Y.; Lin, X.; Yang, Q.; Yang, G. Printability of External and Internal Structures Based on Digital Light Processing 3D Printing Technique. Pharmaceutics 2020, 12, 207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Preetam, S.; Nahak, B.K.; Patra, S.; Toncu, D.C.; Park, S.; Syväjärvi, M.; Orive, G.; Tiwari, A. Emergence of Microfluidics for next Generation Biomedical Devices. Biosens. Bioelectron. X 2022, 10, 100106. [Google Scholar] [CrossRef]
- Pistone, M.; Racaniello, G.F.; Arduino, I.; Laquintana, V.; Lopalco, A.; Cutrignelli, A.; Rizzi, R.; Franco, M.; Lopedota, A.; Denora, N. Direct Cyclodextrin-Based Powder Extrusion 3D Printing for One-Step Production of the BCS Class II Model Drug Niclosamide. Drug Deliv. Transl. Res. 2022, 12, 1895–1910. [Google Scholar] [CrossRef] [PubMed]
- Musgrove, H.B.; Catterton, M.A.; Pompano, R.R. Applied Tutorial for the Design and Fabrication of Biomicrofluidic Devices by Resin 3D Printing. Anal. Chim. Acta 2022, 1209, 339842. [Google Scholar] [CrossRef] [PubMed]
- Bhattacharjee, N.; Urrios, A.; Kang, S.; Folch, A. The Upcoming 3D-Printing Revolution in Microfluidics. Lab Chip 2016, 16, 1720–1742. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, Z.; Tian, X.; Song, X. Engineering Materials with Light: Recent Progress in Digital Light Processing Based 3D Printing. J. Mater. Chem. C Mater. 2020, 8, 13896–13917. [Google Scholar] [CrossRef]
- Krkobabić, M.; Medarević, D.; Cvijić, S.; Grujić, B.; Ibrić, S. Hydrophilic Excipients in Digital Light Processing (DLP) Printing of Sustained Release Tablets: Impact on Internal Structure and Drug Dissolution Rate. Int. J. Pharm. 2019, 572, 118790. [Google Scholar] [CrossRef]
- Tiboni, M.; Tiboni, M.; Pierro, A.; del Papa, M.; Sparaventi, S.; Cespi, M.; Casettari, L. Microfluidics for Nanomedicines Manufacturing: An Affordable and Low-Cost 3D Printing Approach. Int. J. Pharm. 2021, 599, 120464. [Google Scholar] [CrossRef]
- Ballacchino, G.; Weaver, E.; Mathew, E.; Dorati, R.; Genta, I.; Conti, B.; Lamprou, D.A. Manufacturing of 3d-Printed Microfluidic Devices for the Synthesis of Drug-Loaded Liposomal Formulations. Int. J. Mol. Sci. 2021, 22, 8064. [Google Scholar] [CrossRef] [PubMed]
- Weaver, E.; O’Connor, E.; Cole, D.K.; Hooker, A.; Uddin, S.; Lamprou, D.A. Microfluidic-Mediated Self-Assembly of Phospholipids for the Delivery of Biologic Molecules. Int. J. Pharm. 2022, 611, 121347. [Google Scholar] [CrossRef] [PubMed]
- Briuglia, M.L.; Rotella, C.; McFarlane, A.; Lamprou, D.A. Influence of Cholesterol on Liposome Stability and on in Vitro Drug Release. Drug Deliv. Transl. Res. 2015, 5, 231–242. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Weaver, E.; Uddin, S.; Cole, D.K.; Hooker, A.; Lamprou, D.A. The Present and Future Role of Microfluidics for Protein and Peptide-Based Therapeutics and Diagnostics. Appl. Sci. 2021, 11, 4109. [Google Scholar] [CrossRef]
- Pellegrino, L.; Tirelli, A. A Sensitive HPLC Method to Detect Hen’s Egg White Lysozyme in Milk and Dairy Products. Int. Dairy J. 2000, 10, 435–442. [Google Scholar] [CrossRef]
- Whitesides, G.M. The Origins and the Future of Microfluidics. Nature 2006, 442, 368–373. [Google Scholar] [CrossRef]
- DeMello, A.J. Control and Detection of Chemical Reactions in Microfluidic Systems. Nature 2006, 442, 394–402. [Google Scholar] [CrossRef]
- Zhang, Y.; Liu, D.; Zhang, H.; Santos, H.A. Microfluidic Mixing and Devices for Preparing Nanoparticulate Drug Delivery Systems. In Microfluidics for Pharmaceutical Applications: From Nano/Micro Systems Fabrication to Controlled Drug Delivery; Santos, H.A., Liu, D., Zhang, H., Eds.; Elsevier: San Diego, CA, USA, 2018; pp. 155–177. [Google Scholar]
- Aghaei, H.; Solaimany Nazar, A.R. Continuous Production of the Nanoscale Liposome in a Double Flow-Focusing Microfluidic Device. Ind. Eng. Chem. Res. 2019, 58, 23032–23045. [Google Scholar] [CrossRef]
- Carugo, D.; Bottaro, E.; Owen, J.; Stride, E.; Nastruzzi, C. Liposome Production by Microfluidics: Potential and Limiting Factors. Sci. Rep. 2016, 6, 25876. [Google Scholar] [CrossRef] [Green Version]
- Bayareh, M.; Ashani, M.N.; Usefian, A. Active and Passive Micromixers: A Comprehensive Review. Chem. Eng. Process. Process Intensif. 2020, 147, 107771. [Google Scholar] [CrossRef]
- Jain, V.; Patel, V.B.; Singh, B.; Varade, D. Microfluidic Device Based Molecular Self-Assembly Structures. J. Mol. Liq. 2022, 362, 119760. [Google Scholar] [CrossRef]
- Stroock, A.D.; Dertinger, S.K.W.; Ajdari, A.; Mezic, I.M.; Stone, H.A.; Whitesides, G.M. Chaotic Mixer for Microchannels. Science 2002, 295, 647–651. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Niculescu, A.G.; Chircov, C.; Bîrcă, A.C.; Grumezescu, A.M. Fabrication and Applications of Microfluidic Devices: A Review. Int. J. Mol. Sci. 2021, 22, 2011. [Google Scholar] [CrossRef] [PubMed]
- Park, H.; Otte, A.; Park, K. Evolution of Drug Delivery Systems: From 1950 to 2020 and Beyond. J. Control. Release 2022, 342, 53–65. [Google Scholar] [CrossRef]
- Bozzuto, G.; Molinari, A. Liposomes as Nanomedical Devices. Int. J. Nanomed. 2015, 10, 975–999. [Google Scholar] [CrossRef] [Green Version]
- Elsana, H.; Olusanya, T.O.B.; Car-Wilkinson, J.; Darby, S.; Faheem, A.; Elkordy, A.A. Evaluation of novel cationic lipid based liposomes with cyclodextrin prepared by thin film hydration and microfluidic systems. Sci. Rep. 2019, 9, 15120. [Google Scholar] [CrossRef] [Green Version]
- Al-Amin, M.D.; Bellato, F.; Matrotto, F.; Garofalo, M.; Malfanti, A.; Salmaso, S.; Caliceti, P. Dexamethasone Loaded Liposomes by Thin-Film Hydration and Microfluidic Procedures: Formulation Challenges. Int. J. Mol. Sci. 2020, 21, 1611. [Google Scholar] [CrossRef] [Green Version]
- Roces, C.B.; Lou, G.; Jain, N.; Abraham, S.; Thomas, A.; Halbert, G.W.; Perrie, Y. Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics. Pharmaceutics 2020, 12, 1095. [Google Scholar] [CrossRef]
- Maeki, M.; Fujishima, Y.; Sato, Y.; Yasui, T.; Kaji, N.; Ishida, A.; Tani, H.; Baba, Y.; Harashima, H.; Tokeshi, M. Understanding the Formation Mechanism of Lipid Nanoparticles in Microfluidic Devices with Chaotic Micromixers. PLoS ONE 2017, 12, e0187962. [Google Scholar] [CrossRef]
- Antonietti, M.; Förster, S. Vesicles and Liposomes: A Self-Assembly Principle Beyond Lipids. Adv. Mater. 2003, 15, 1323–1333. [Google Scholar] [CrossRef]
- Doskocz, J.; Dałek, P.; Foryś, A.; Trzebicka, B.; Przybyło, M.; Mesarec, L.; Iglič, A.; Langner, M. The Effect of Lipid Phase on Liposome Stability upon Exposure to the Mechanical Stress. Biochim. Biophys. Acta Biomembr. 2020, 1862, 183361. [Google Scholar] [CrossRef] [PubMed]
- Martins, J.P.; Torrieri, G.; Santos, H.A. The Importance of Microfluidics for the Preparation of Nanoparticles as Advanced Drug Delivery Systems. Expert Opin. Drug Deliv. 2018, 15, 469–479. [Google Scholar] [CrossRef] [PubMed]
- Belliveau, N.M.; Huft, J.; Lin, P.J.; Chen, S.; Leung, A.K.; Leaver, T.J.; Wild, A.W.; Lee, J.B.; Taylor, R.J.; Tam, Y.K.; et al. Microfluidic Synthesis of Highly Potent Limit-Size Lipid Nanoparticles for in Vivo Delivery of SiRNA. Mol. Ther. Nucleic Acids 2012, 1, e37. [Google Scholar] [CrossRef] [PubMed]
- Fritea, L.; Cavalu, S. Formulation, Characterization, and Advantages of Using Liposomes in Multiple Therapies. Pharmacophore 2020, 11, 1–12. [Google Scholar]
- Tai, K.; Rappolt, M.; Mao, L.; Gao, Y.; Yuan, F. Stability and Release Performance of Curcumin-Loaded Liposomes with Varying Content of Hydrogenated Phospholipids. Food Chem. 2020, 326, 126973. [Google Scholar] [CrossRef]
- Jain, A.; Jain, S.K. In Vitro Release Kinetics Model Fitting of Liposomes: An Insight. Chem. Phys. Lipids 2016, 201, 28–40. [Google Scholar] [CrossRef]
- Haidar, Z.S.; Hamdy, R.C.; Tabrizian, M. Protein Release Kinetics for Core-Shell Hybrid Nanoparticles Based on the Layer-by-Layer Assembly of Alginate and Chitosan on Liposomes. Biomaterials 2008, 29, 1207–1215. [Google Scholar] [CrossRef]
- Morgenstern, J.; Baumann, P.; Brunner, C.; Hubbuch, J. Effect of PEG Molecular Weight and PEGylation Degree on the Physical Stability of PEGylated Lysozyme. Int. J. Pharm. 2017, 519, 408–417. [Google Scholar] [CrossRef]
- Forbes, N.; Hussain, M.T.; Briuglia, M.L.; Edwards, D.P.; ter Horst, J.H.; Szita, N.; Perrie, Y. Rapid and Scale-Independent Microfluidic Manufacture of Liposomes Entrapping Protein Incorporating in-Line Purification and at-Line Size Monitoring. Int. J. Pharm. 2019, 556, 68–81. [Google Scholar] [CrossRef] [Green Version]
- Mohammed, A.R.; Weston, N.; Coombes, A.G.A.; Fitzgerald, M.; Perrie, Y. Liposome Formulation of Poorly Water Soluble Drugs: Optimisation of Drug Loading and ESEM Analysis of Stability. Int. J. Pharm. 2004, 285, 23–34. [Google Scholar] [CrossRef]
Device | Angle (°) | Channel Type | Geometry | Dimensions (mm) | Internal Geometry (mm) |
---|---|---|---|---|---|
1 | 90 | Round | Diamond | 1.0 × 1.0 × 2.30 | - |
2 | 45 | Round | Diamond | 1.0 × 1.0 × 2.30 | - |
3 | 90 | Square | Diamond + wedges (internal) | 1.0 × 1.0 × 2.30 | 0.8 × 0.8 × 0.8 |
4 | 90 | Square | Diamond + herringbone (internal) | 1.0 × 1.0 × 2.30 | 0.8 × 1.94 × 1.22 |
5 | 90 | Square | Diamond | 1.0 × 1.0 × 2.30 | - |
6 | 45 | Square | Diamond | 1.0 × 1.0 × 2.30 | - |
Device | FRRs (PBS: Organic Phase) | |||||
---|---|---|---|---|---|---|
5:0.5 | 5:1 | 5:3 | ||||
Particle Size (nm) | PDI | Particle Size (nm) | PDI | Particle Size (nm) | PDI | |
1 | 111.55 ± 4.56 | 0.19 ± 0.03 | 181.42 ± 11.53 | 0.17 ± 0.04 | 148.21 ± 4.77 | 0.08 ± 0.03 |
2 | 123.39 ± 2.21 | 0.19 ± 0.02 | 180.37 ± 11.35 | 0.22 ± 0.01 | 141.15 ± 1.72 | 0.09 ± 0.04 |
3 | 136.71 ± 12.07 | 0.21 ± 0.02 | 204.44 ± 36.11 | 0.16 ± 0.04 | 171.25 ± 2.58 | 0.08 ± 0.04 |
4 | 125.62 ± 4.33 | 0.14 ± 0.03 | 169.08 ± 8.63 | 0.19 ± 0.04 | 140.97 ± 2.46 | 0.12 ± 0.03 |
5 | 194.71 ± 38.86 | 0.20 ± 0.04 | 302.55 ± 20.72 | 0.23 ± 0.01 | 164.50 ± 9.83 | 0.16 ± 0.04 |
6 | 134.38 ± 5.12 | 0.22 ± 0.01 | 147.86 ± 2.58 | 0.17 ± 0.02 | 152.84 ± 2.00 | 0.09 ± 0.02 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 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 (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Sommonte, F.; Weaver, E.; Mathew, E.; Denora, N.; Lamprou, D.A. In-House Innovative “Diamond Shaped” 3D Printed Microfluidic Devices for Lysozyme-Loaded Liposomes. Pharmaceutics 2022, 14, 2484. https://doi.org/10.3390/pharmaceutics14112484
Sommonte F, Weaver E, Mathew E, Denora N, Lamprou DA. In-House Innovative “Diamond Shaped” 3D Printed Microfluidic Devices for Lysozyme-Loaded Liposomes. Pharmaceutics. 2022; 14(11):2484. https://doi.org/10.3390/pharmaceutics14112484
Chicago/Turabian StyleSommonte, Federica, Edward Weaver, Essyrose Mathew, Nunzio Denora, and Dimitrios A. Lamprou. 2022. "In-House Innovative “Diamond Shaped” 3D Printed Microfluidic Devices for Lysozyme-Loaded Liposomes" Pharmaceutics 14, no. 11: 2484. https://doi.org/10.3390/pharmaceutics14112484