Rifampicin–Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Liposomes and Rifampicin-Loaded Liposomes
2.3. Rifampicin Entrapment Efficiency (EE%)
2.4. In Vitro Release Studies
2.5. Size and ζ-Potential Measurements
2.6. Morphological Investigation
2.7. Physicochemical Stability
2.8. Bilayer Characterization by DPH Fluorescence Anisotropy
2.9. Biological Evaluation
2.9.1. Bacterial Strains
2.9.2. Cell Line
2.9.3. Mabs Bacteria Infection
2.9.4. Direct Effect of Rifampicin on Mabs
2.9.5. Stability of Liposomes in Culture Medium
2.9.6. Effect of Rifampicin and Rifampicin-Loaded Liposomes on dTHP-1
2.9.7. Uptake of Liposomes in dTHP-1 Cells
2.10. Statistical Analysis
3. Results and Discussion
3.1. Characterization of Liposomes
3.1.1. Physicochemical Features of Liposomal Formulations
3.1.2. Physicochemical Stability
3.1.3. Morphological Investigation
3.1.4. Rifampicin Release Profile
3.2. Biological Evaluation of RIF-Loaded Liposomes
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Lopeman, R.; Harrison, J.; Desai, M.; Cox, J. Mycobacterium abscessus: Environmental Bacterium Turned Clinical Nightmare. Microorganisms 2019, 7, 90. [Google Scholar] [CrossRef] [Green Version]
- Ryan, K.; Byrd, T.F. Mycobacterium abscessus: Shapeshifter of the Mycobacterial World. Front. Microbiol. 2018, 9, 2642. [Google Scholar] [CrossRef] [PubMed]
- Nessar, R.; Cambau, E.; Reyrat, J.M.; Murray, A.; Gicquel, B. Mycobacterium abscessus: A New Antibiotic Nightmare. J. Antimicrob. Chemother. 2012, 67, 810–818. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yeh, Y.-C.; Huang, T.-H.; Yang, S.-C.; Chen, C.-C.; Fang, J.-Y. Nano-Based Drug Delivery or Targeting to Eradicate Bacteria for Infection Mitigation: A Review of Recent Advances. Front. Chem. 2020, 8, 286. [Google Scholar] [CrossRef] [PubMed]
- Antimisiaris, S.G.; Marazioti, A.; Kannavou, M.; Natsaridis, E.; Gkartziou, F.; Kogkos, G.; Mourtas, S. Overcoming Barriers by Local Drug Delivery with Liposomes. Adv. Drug Deliv. Rev. 2021, 174, 53–86. [Google Scholar] [CrossRef]
- Baranyai, Z.; Soria Carrera, H.; Alleva, M.; Millán Placer, A.C.; Lucía, A.; Martín Rapún, R.; Aínsa, J.A.; la Fuente, J.M. Nanotechnology Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis. Adv. Therap. 2021, 4, 2000113. [Google Scholar] [CrossRef]
- Shirley, M. Amikacin Liposome Inhalation Suspension: A Review in Mycobacterium abscessus: Complex Lung Disease. Drugs 2019, 79, 555–562. [Google Scholar] [CrossRef] [Green Version]
- Novosad, S.A.; Beekmann, S.E.; Polgreen, P.M.; Mackey, K.; Winthrop, K.L. Treatment of Mycobacterium abscessus: Infection. Emerg. Infect. Dis. 2016, 22, 511–514. [Google Scholar] [CrossRef] [Green Version]
- Daniel-Wayman, S.; Abate, G.; Barber, D.L.; Bermudez, L.E.; Coler, R.N.; Cynamon, M.H.; Daley, C.L.; Davidson, R.M.; Dick, T.; Floto, R.A.; et al. Advancing Translational Science for Pulmonary Nontuberculous Mycobacterial Infections. A Road Map for Research. Am. J. Respir. Crit. Care Med. 2019, 199, 947–951. [Google Scholar] [CrossRef]
- Sarathy, J.P.; Via, L.E.; Weiner, D.; Blanc, L.; Boshoff, H.; Eugenin, E.A.; Barry, C.E.; Dartois, V.A. Extreme Drug Tolerance of Mycobacterium abscessus: In Caseum. Antimicrob. Agents Chemother. 2017, 62, e02266-17. [Google Scholar] [CrossRef] [Green Version]
- Aziz, D.B.; Low, J.L.; Wu, M.-L.; Gengenbacher, M.; Teo, J.W.P.; Dartois, V.; Dick, T. Rifabutin Is Active against Mycobacterium abscessus: Complex. Antimicrob. Agents Chemother. 2017, 61, e00155-17. [Google Scholar] [CrossRef] [Green Version]
- Garhyan, J.; Mohan, S.; Rajendran, V.; Bhatnagar, R. Preclinical Evidence of Nanomedicine Formulation to Target Mycobacterium abscessus: At Its Bone Marrow Niche. Pathogens 2020, 9, 372. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Q.; Leung, S.S.Y.; Tang, P.; Parumasivam, T.; Loh, Z.H.; Chan, H.-K. Inhaled Formulations and Pulmonary Drug Delivery Systems for Respiratory Infections. Adv. Drug Deliv. Rev. 2015, 85, 83–99. [Google Scholar] [CrossRef]
- Lunov, O.; Syrovets, T.; Loos, C.; Beil, J.; Delacher, M.; Tron, K.; Nienhaus, G.U.; Musyanovych, A.; Mailänder, V.; Landfester, K.; et al. Differential Uptake of Functionalized Polystyrene Nanoparticles by Human Macrophages and a Monocytic Cell Line. ACS Nano 2011, 5, 1657–1669. [Google Scholar] [CrossRef] [PubMed]
- Vyas, S.P.; Kannan, M.E.; Jain, S.; Mishra, V.; Singh, P. Design of Liposomal Aerosols for Improved Delivery of Rifampicin to Alveolar Macrophages. Int. J. Pharm. 2004, 269, 37–49. [Google Scholar] [CrossRef]
- Ways, T.M.; Lau, W.; Khutoryanskiy, V. Chitosan and Its Derivatives for Application in Mucoadhesive Drug Delivery Systems. Polymers 2018, 10, 267. [Google Scholar] [CrossRef] [Green Version]
- Brennan, P.; Young, D. Rifampin. Tuberculosis (Edinb.) 2008, 88, 151–154. [Google Scholar]
- Ingallina, C.; Rinaldi, F.; Bogni, A.; Ponti, J.; Passeri, D.; Reggente, M.; Rossi, M.; Kinsner-Ovaskainen, A.; Mehn, D.; Rossi, F.; et al. Niosomal Approach to Brain Delivery: Development, Characterization and in Vitro Toxicological Studies. Int. J. Pharm. 2016, 511, 969–982. [Google Scholar] [CrossRef]
- Zaborniak, I.; Macior, A.; Chmielarz, P. Stimuli-Responsive Rifampicin-Based Macromolecules. Materials 2020, 13, 3843. [Google Scholar] [CrossRef]
- Koppel, D.E. Analysis of Macromolecular Polydispersity in Intensity Correlation Spectroscopy: The Method of Cumulants. J. Chem. Phys. 1972, 57, 4814–4820. [Google Scholar] [CrossRef]
- Tucker, I.M.; Corbett, J.C.W.; Fatkin, J.; Jack, R.O.; Kaszuba, M.; MacCreath, B.; McNeil-Watson, F. Laser Doppler Electrophoresis Applied to Colloids and Surfaces. Curr. Opin. Colloid Interface Sci. 2015, 20, 215–226. [Google Scholar] [CrossRef]
- Aleandri, S.; Bonicelli, M.G.; Bordi, F.; Casciardi, S.; Diociaiuti, M.; Giansanti, L.; Leonelli, F.; Mancini, G.; Perrone, G.; Sennato, S. How Stereochemistry Affects the Physicochemical Features of Gemini Surfactant Based Cationic Liposomes. Soft Matter 2012, 8, 5904. [Google Scholar] [CrossRef]
- Lentz, B.R. Membrane “Fluidity” as Detected by Diphenylhexatriene Probes. Chem. Phys. Lipids 1989, 50, 171–190. [Google Scholar] [CrossRef]
- Sciolla, F.; Truzzolillo, D.; Chauveau, E.; Trabalzini, S.; Di Marzio, L.; Carafa, M.; Marianecci, C.; Sarra, A.; Bordi, F.; Sennato, S. Influence of Drug/Lipid Interaction on the Entrapment Efficiency of Isoniazid in Liposomes for Antitubercular Therapy: A Multi-Faced Investigation. arXiv 2021, arXiv:2101.10900. [Google Scholar]
- Foroozandeh, P.; Aziz, A.A. Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles. Nanoscale Res. Lett. 2018, 13, 339. [Google Scholar] [CrossRef]
- Crommelin, D.J.A. Influence of Lipid Composition and Ionic Strength on the Physical Stability of Liposomes. J. Pharm. Sci. 1984, 73, 1559–1563. [Google Scholar] [CrossRef]
- Patel, V.R.; Agrawal, Y.K. Nanosuspension: An Approach to Enhance Solubility of Drugs. J. Adv. Pharm. Technol. Res. 2011, 2, 81–87. [Google Scholar] [CrossRef]
- Zuidam, N.J.; Gouw, H.K.M.E.; Barenholz, Y.; Crommelin, D.J.A. Physical (in) Stability of Liposomes upon Chemical Hydrolysis: The Role of Lysophospholipids and Fatty Acids. Biochim. Biophys. Acta (BBA) Biomembr. 1995, 1240, 101–110. [Google Scholar] [CrossRef] [Green Version]
- Rodrigues, C.; Gameiro, P.; Prieto, M.; de Castro, B. Interaction of Rifampicin and Isoniazid with Large Unilamellar Liposomes: Spectroscopic Location Studies. Biochim. Biophys. Acta (BBA) Gen. Subj. 2003, 1620, 151–159. [Google Scholar] [CrossRef]
- Rodrigues, C.; Gameiro, P.; Reis, S.; de Castro, B. Derivative Spectrophotometry as a Tool for the Determination of Drug Partition Coefficients in Waterrdimyristoyl-L-α-Phosphatidylglycerol ž DMPG/ Liposomes. Biophys. Chem. 2001, 94, 97–106. [Google Scholar] [CrossRef]
- Zaru, M.; Mourtas, S.; Klepetsanis, P.; Fadda, A.M.; Antimisiaris, S.G. Liposomes for Drug Delivery to the Lungs by Nebulization. Eur. J. Pharm. Biopharm. 2007, 67, 655–666. [Google Scholar] [CrossRef]
- Sorokoumova, G.M.; Vostrikov, V.V.; Selishcheva, A.A.; Rogozhkina, E.A.; Kalashnikova, T.Y.; Shvets, V.I.; Golyshevskaya, V.I.; Martynova, L.P.; Erokhin, V.V. Bacteriostatic Activity and Decomposition Products of Rifampicin in Aqueous Solution and Liposomal Composition. Pharm. Chem. J. 2008, 42, 475–478. [Google Scholar] [CrossRef]
- Ruozi, B.; Belletti, D.; Tombesi, A.; Tosi, G.; Bondioli, L.; Forni, F.; Vandelli, M.A. AFM, ESEM, TEM, and CLSM in Liposomal Characterization: A Comparative Study. Int. J. Nanomed. 2011, 557. [Google Scholar] [CrossRef] [Green Version]
- Jass, J.; Tjärnhage, T.; Puu, G. From Liposomes to Supported, Planar Bilayer Structures on Hydrophilic and Hydrophobic Surfaces: An Atomic Force Microscopy Study. Biophys. J. 2000, 79, 3153–3163. [Google Scholar] [CrossRef] [Green Version]
- Reviakine, I.; Brisson, A. Formation of Supported Phospholipid Bilayers from Unilamellar Vesicles Investigated by Atomic Force Microscopy. Langmuir 2000, 16, 1806–1815. [Google Scholar] [CrossRef]
- Pignataro, B.; Steinem, C.; Galla, H.-J.; Fuchs, H.; Janshoff, A. Specific Adhesion of Vesicles Monitored by Scanning Force Microscopy and Quartz Crystal Microbalance. Biophys. J. 2000, 78, 487–498. [Google Scholar] [CrossRef] [Green Version]
- Kalghatgi, S.; Spina, C.S.; Costello, J.C.; Liesa, M.; Morones-Ramirez, J.R.; Slomovic, S.; Molina, A.; Shirihai, O.S.; Collins, J.J. Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells. Sci. Transl. Med. 2013, 5, 192ra85. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Sample | DPPG (mg/mL) | HSPC (mg/mL) | RIF (mg/mL) |
---|---|---|---|
Lipo | 5 | 5 | 0 |
RIF–Lipo | 5 | 5 | 5 |
Sample | Hydrodynamic Diameter ± SD (nm) | PDI ± SD | ζ-Potential ± SD (mV) | RIF EE% | Anisotropy (r) ± SD |
---|---|---|---|---|---|
Lipo | 127.6 ± 0.8 | 0.20 ± 0.01 | −55.4 ± 1.6 | - | 0.39 ± 0.03 |
RIF–Lipo | 116.7 ± 0.9 | 0.20 ± 0.01 | −41.7 ± 2.0 | 96 ± 10 | 0.34 ± 0.02 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 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
Rinaldi, F.; Hanieh, P.N.; Sennato, S.; De Santis, F.; Forte, J.; Fraziano, M.; Casciardi, S.; Marianecci, C.; Bordi, F.; Carafa, M. Rifampicin–Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation. Pharmaceutics 2021, 13, 1070. https://doi.org/10.3390/pharmaceutics13071070
Rinaldi F, Hanieh PN, Sennato S, De Santis F, Forte J, Fraziano M, Casciardi S, Marianecci C, Bordi F, Carafa M. Rifampicin–Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation. Pharmaceutics. 2021; 13(7):1070. https://doi.org/10.3390/pharmaceutics13071070
Chicago/Turabian StyleRinaldi, Federica, Patrizia Nadia Hanieh, Simona Sennato, Federica De Santis, Jacopo Forte, Maurizio Fraziano, Stefano Casciardi, Carlotta Marianecci, Federico Bordi, and Maria Carafa. 2021. "Rifampicin–Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation" Pharmaceutics 13, no. 7: 1070. https://doi.org/10.3390/pharmaceutics13071070
APA StyleRinaldi, F., Hanieh, P. N., Sennato, S., De Santis, F., Forte, J., Fraziano, M., Casciardi, S., Marianecci, C., Bordi, F., & Carafa, M. (2021). Rifampicin–Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation. Pharmaceutics, 13(7), 1070. https://doi.org/10.3390/pharmaceutics13071070