Drug Transport System Based on Phospholipid Nanoparticles: Production Technology and Characteristics
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Preparation of Phospholipid Nanoparticles
2.2.2. Determination of Particle Size
2.2.3. Determination of the ζ-Potential Value
2.2.4. Incorporation of Drug into Phospholipid Nanoparticles
2.2.5. Measurement of the Percentage of a Drug in Nanoparticles
2.2.6. Drug Release In Vitro
2.2.7. Determination of Moisture Content
2.2.8. Statistics
3. Results and Discussion
3.1. Optimization of High-Pressure Homogenization
3.2. Influence of Other Parameters on the Size of Phospholipid Nanoparticles
3.3. Standardization of Particle Size and Sterilizing Filtration
3.4. Selection of a Cryoprotectant and Optimization of Freeze Drying Process
- Freezing of the product to a temperature of −40 °C;
- Reduction of the temperature to −50 °C by additional two-hours of freezing;
- Lyophilization at a product temperature −21.5 °C and a shelf temperature of 20 °C for 500–1000 min (depending on the amount of drying material);
- Secondary drying step at a shelf temperature of 40 °C for 500–1000 min (depending on the amount of drying material).
3.5. Physical Properties of Phospholipid Nanoparticles
3.5.1. Laser Correlation Spectroscopy (Dynamic Light Scattering)
3.5.2. Transmission Electron Microscopy
3.5.3. Electrokinetic Potential (Zeta Potential (ζ))
3.6. Incorporation of Drugs
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Marx, U.; Akabane, T.; Andersson, T.B.; Baker, E.; Beilmann, M.; Beken, S.; Brendler-Schwaab, S.; Cirit, M.; David, R.; Dehne, E.; et al. Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development. Altex 2020, 37, 365–394. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Petros, R.A.; DeSimone, J.M. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 2010, 9, 615–627. [Google Scholar] [CrossRef] [PubMed]
- Bayón-Cordero, L.; Alkorta, I.; Arana, L. Application of solid lipid nanoparticles to improve the efficiency of anticancer drugs. Nanomaterials 2019, 9, 474. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cojocaru, F.D.; Botezat, D.; Gardikiotis, I.; Uritu, C.M.; Dodi, G.; Trandafir, L.; Rezus, C.; Rezus, E.; Tamba, B.I.; Mihai, C.T. Nanomaterials designed for antiviral drug delivery transport across biological barriers. Pharmaceutics 2020, 12, 171. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, X.H.; Zhang, D.W.; Zheng, X.L.; Tang, C.K. Cholesterol transport system: An integrated cholesterol transport model involved in atherosclerosis. Prog. Lipid Res. 2019, 73, 65–91. [Google Scholar] [CrossRef] [PubMed]
- McCormick, S.C.; Stillman, N.; Hockley, M.; Perriman, A.W.; Hauert, S. Measuring Nanoparticle Penetration Through Bio-Mimetic Gels. Int. J. Nanomed. 2021, 16, 2585–2595. [Google Scholar] [CrossRef]
- Sur, S.; Rathore, A.; Dave, V.; Reddy, K.R.; Chouhan, R.S.; Sadhu, V. Recent developments in functionalized polymer nanoparticles for efficient drug delivery system. Nano-Struct. Nano-Objects 2019, 20, 100397. [Google Scholar] [CrossRef]
- Drescher, S.; van Hoogevest, P. The phospholipid research center: Current research in phospholipids and their use in drug delivery. Pharmaceutics 2020, 12, 1235. [Google Scholar] [CrossRef]
- Danaei, M.; Dehghankhold, M.; Ataei, S.; Hasanzadeh Davarani, F.; Javanmard, R.; Dokhani, A.; Khorasani, S.; Mozafari, M.R. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018, 10, 57. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Grainger, D.W. Lyophilized liposome-based parenteral drug development: Reviewing complex product design strategies and current regulatory environments. Adv. Drug Deliv. Rev. 2019, 151, 56–71. [Google Scholar] [CrossRef]
- Zhang, X.; Shao, X.; Cai, Z.; Yan, X.; Zong, W. The fabrication of phospholipid vesicle-based artificial cells and their functions. N. J. Chem. 2021, 45, 3364. [Google Scholar] [CrossRef]
- Li, Y.; Xiang, D. Stability of oil-in-water emulsions performed by ultrasound power or high-pressure homogenization. PLoS ONE 2019, 14, e0213189. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Musielak, E.; Feliczak-Guzik, A.; Nowak, I. Synthesis and potential applications of lipid nanoparticles in medicine. Materials 2022, 15, 682. [Google Scholar] [CrossRef]
- Hauser, H. Phospholipid vesicles. In Phospholipids Handbook; Cevk, G., Ed.; Marcel Dekker, Inc.: New York, NY, USA, 1993; Volume 17, pp. 603–637. [Google Scholar]
- Xu, B.; Yuan, L.; Hu, Y.; Xu, Z.; Qin, J.J.; Cheng, X.D. Synthesis, characterization, cellular uptake, and in vitro anticancer activity of fullerenol-doxorubicin conjugates. Front. Pharmacol. 2021, 11, 598155. [Google Scholar] [CrossRef]
- Mahdi Jafari, S.; He, Y.; Bhandari, B. Nano-emulsion production by sonication and microfluidization—A comparison. Int. J. Food Prop. 2006, 9, 475–485. [Google Scholar] [CrossRef]
- Vemuri, S.; Yu, C.D.; Wangsatorntanakun, V.; Roosdorp, N. Large-scale production of liposomes by a microfluidizer. Drug Dev. Ind. Pharm. 2008, 16, 2243–2256. [Google Scholar] [CrossRef]
- Thompson, A.K.; Mozafari, M.R.; Singh, H. The properties of liposomes produced from milk fat globule membrane material using different techniques. Le Lait 2007, 87, 349–360. [Google Scholar] [CrossRef]
- Carugo, D.; Bottaro, E.; Owen, J.; Stride, E.; Nastruzzi, C. Liposome production by microfluidics: Potential and limiting factors. Sci. Rep. 2020, 6, 25876. [Google Scholar] [CrossRef] [Green Version]
- Rezvankhah, A.; Emam-Djomeh, Z.; Askari, G. Encapsulation and delivery of bioactive compounds using spray and freeze-drying techniques: A review. Dry. Technol. 2020, 38, 235–258. [Google Scholar] [CrossRef]
- Wang, L.; Ma, Y.; Gu, Y.; Liu, Y.; Zhao, J.; Yan, B.; Wang, Y. Cryoprotectant choice and analyses of freeze-drying drug suspension of nanoparticles with functional stabilisers. J. Microencapsul. 2018, 35, 241–248. [Google Scholar] [CrossRef]
- Lombardo, D.; Kiselev, M.A. Methods of liposomes preparation: Formation and control factors of versatile nanocarriers for biomedical and nanomedicine application. Pharmaceutics 2022, 14, 543. [Google Scholar] [CrossRef]
- Zemlyanaya, E.V.; Kiselev, M.A.; Zhabitskaya, E.I.; Aksenov, V.L.; Ipatova, O.M.; Ivankov, O.I. The small-angle neutron scattering data analysis of the phospholipid transport nanosystem structure. J. Phys. Conf. Ser. 2018, 1023, 012017. [Google Scholar] [CrossRef]
- Bashashin, M.; Zemlyanaya, E.; Zhabitskaya, E.; Kiselev, M.; Sapozhnikova, T. Determination of the vesicular systems parameters: Parallel implementation and analysis of the PTNS vesicle structure. EPJ Web Conf. 2018, 173, 05003. [Google Scholar] [CrossRef] [Green Version]
- Xian, H.W.; Sidik, N.A.C.; Saidur, R. Impact of different surfactants and ultrasonication time on the stability and thermophysical properties of hybrid nanofluids. Int. Commun. Heat Mass Transf. 2020, 110, 104389. [Google Scholar] [CrossRef]
- Ahmed, K.S.; Hussein, S.A.; Ali, A.H.; Korma, S.A.; Lipeng, Q.; Jinghua, C. Liposome: Composition, characterisation, preparation, and recent innovation in clinical applications. J. Drug Target. 2019, 27, 742–761. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Wang, Y.; Liang, W. Delivery of drugs to cell membranes by encapsulation in PEG–PE micelles. J. Control. Release 2012, 160, 637–651. [Google Scholar] [CrossRef]
- Rommasi, F.; Esfandiari, N. Liposomal nanomedicine: Applications for drug delivery in cancer therapy. Nanoscale Res. Lett. 2021, 16, 95. [Google Scholar] [CrossRef]
Drug | Elution | Detection (Signal/Reference, nm) | Retention Time, min |
---|---|---|---|
Doxorubicin | 30–90% B—0–10 min | 254/360 | 6.3 |
Indomethacin | 60% B—10 min | 254/360 | 8.5 |
Umifenovir | 0–60% B—0–5 min 60% B—5–15 min | 254/360 | 11.4 |
Diclofenac | 60% B—13 min | 280/360 | 8.6 |
Budesonid | 75% B—8 min | 243/360 | 4.4 |
Prednisolon | 10–60% B—0–5 min 60% B—5–12 min | 240/360 | 8.4 |
Chlorine e6 | 60–99% B—0–1 min 99% B—1–10 min | 400/460 | 4.4 |
Drug | Particle Size, nm | Zeta Potential, mV | Content of Drug, mg | Percentage of Drug in Nanoparticles, % |
---|---|---|---|---|
Phospholipid nanoparticles | 28.9 ± 1.2 | −3.9 ± 1.1 | - | - |
Doxorubicin | 19.2 ± 3.1 | 6.5 ± 0.8 | 13.0 | 96 |
Indomethacin | 21.9 ± 1.9 | −12.9 ± 0.6 | 23.8 | 95 |
Umifenovir | 8.4 ± 2.6 | 43.8 ± 1.8 | 24.6 | 98.3 |
Diclofenac | 12.9 ± 3.0 | −46.6 ± 1.5 | 23.0 | 92 |
Budesonid | 22.4 ± 4.6 | −1.6 ± 0.2 | 5.0 | 100 |
Prednisolon | 18.3 ± 4.1 | −4.6 ± 1.3 | 14.7 | 98 |
Chlorin e6 | 21.2 ± 3.3 | −25.5 ± 4.0 | 12.3 | 98.4 |
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Tikhonova, E.G.; Sanzhakov, M.A.; Tereshkina, Y.A.; Kostryukova, L.V.; Khudoklinova, Y.Y.; Orlova, N.A.; Bobrova, D.V.; Ipatova, O.M. Drug Transport System Based on Phospholipid Nanoparticles: Production Technology and Characteristics. Pharmaceutics 2022, 14, 2522. https://doi.org/10.3390/pharmaceutics14112522
Tikhonova EG, Sanzhakov MA, Tereshkina YA, Kostryukova LV, Khudoklinova YY, Orlova NA, Bobrova DV, Ipatova OM. Drug Transport System Based on Phospholipid Nanoparticles: Production Technology and Characteristics. Pharmaceutics. 2022; 14(11):2522. https://doi.org/10.3390/pharmaceutics14112522
Chicago/Turabian StyleTikhonova, Elena G., Maxim A. Sanzhakov, Yulia A. Tereshkina, Lyubov V. Kostryukova, Yulia Yu. Khudoklinova, Nadezhda A. Orlova, Daria V. Bobrova, and Olga M. Ipatova. 2022. "Drug Transport System Based on Phospholipid Nanoparticles: Production Technology and Characteristics" Pharmaceutics 14, no. 11: 2522. https://doi.org/10.3390/pharmaceutics14112522
APA StyleTikhonova, E. G., Sanzhakov, M. A., Tereshkina, Y. A., Kostryukova, L. V., Khudoklinova, Y. Y., Orlova, N. A., Bobrova, D. V., & Ipatova, O. M. (2022). Drug Transport System Based on Phospholipid Nanoparticles: Production Technology and Characteristics. Pharmaceutics, 14(11), 2522. https://doi.org/10.3390/pharmaceutics14112522