Abstract
With the recent increase in lung diseases, especially with the onset of the coronavirus pandemic, the design of a highly efficient and optimal targeted drug delivery system for the lungs is crucial in inhaler-based delivery systems. This study aimed to design a magnetic field-assisted targeted drug delivery system to the lungs using three types of metal–organic frameworks (MOFs) and nanoliposomes. The optimization of the system was based on three main parameters: the surface density of the nanocarriers' (NCs) adherence to each of the lung branches, the amount of drug transferred to each branch, and the toxicity based on the rate of nanocarrier delivery to the branches. The study investigated the effect of increasing the diameter of the drug carriers and the amount of drug loaded onto the NCs in improving drug delivery to targeted areas of the lung. Results showed that the presence of a magnetic field significantly increased the adhesion of NCs to the targeted branches. The application of a magnetic field and the type of drug carrier had a significant effect on drug delivery downstream of the lung and reduced drug toxicity. The study found that Fe3O4@UiO-66 (iron-oxide nanoparticle attached to the surface of UiO-66, a type of MOF) and Fe3O4@PAA/AuNCs/ZIF-8 carriers, (iron-oxide nanoparticle attached to a hybrid structure composed of three different materials: poly (acrylic acid) (PAA), gold nanoclusters (AuNCs), and zeolitic imidazolate framework-8 (ZIF-8)), had the greatest drug delivery rate in diameters above 200 nm and less than 200 nm, respectively.
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All data, models, or code generated or used during the study are available from the corresponding author upon reasonable request.
References
Ahmed SA, Giddens DP (1983) Velocity measurements in steady flow through axisymmetric stenoses at moderate Reynolds numbers. J Biomech. https://doi.org/10.1016/0021-9290(83)90065-9
Alishiri M, Ebrahimi S, Shamloo A et al (2021) Drug delivery and adhesion of magnetic nanoparticles coated nanoliposomes and microbubbles to atherosclerotic plaques under magnetic and ultrasound fields. Eng Appl Comput Fluid Mech 15:1703–1725. https://doi.org/10.1080/19942060.2021.1989042
Alvizo-Baez CA, Luna-Cruz IE, Vilches-Cisneros N et al (2016) Systemic delivery and activation of the TRAIL gene in lungs, with magnetic nanoparticles of chitosan controlled by an external magnetic field. Int J Nanomed 11:6449–6458. https://doi.org/10.2147/IJN.S118343
Amani A, Shamloo A, Barzegar S, Forouzandehmehr M (2021) Effect of material and population on the delivery of nanoparticles to an atherosclerotic plaque: a patient-specific in silico study. Langmuir. https://doi.org/10.1021/acs.langmuir.0c03158
Babinec P, Krafčík A, Babincová M, Rosenecker J (2010) Dynamics of magnetic particles in cylindrical Halbach array: implications for magnetic cell separation and drug targeting. Med Biol Eng Comput 48:745–753. https://doi.org/10.1007/s11517-010-0636-8
Bangham AD, Standish MM, Watkins JC (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. https://doi.org/10.1016/S0022-2836(65)80093-6
Barrefelt Å, Saghafian M, Kuiper R et al (2013) Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat. Int J Nanomed 8:3241–3254. https://doi.org/10.2147/IJN.S49948
Bian R, Wang T, Zhang L et al (2015) A combination of tri-modal cancer imaging and in vivo drug delivery by metal-organic framework based composite nanoparticles. Biomater Sci 3:1270–1278. https://doi.org/10.1039/c5bm00186b
Biglari H, Razaghi R, Ebrahimi S, Karimi A (2019) A computational dynamic finite element simulation of the thoracic vertebrae under blunt loading: spinal cord injury. J Brazilian Soc Mech Sci Eng 41:84. https://doi.org/10.1007/s40430-019-1588-z
Camacho JM, Sosa V (2013) Alternative method to calculate the magnetic field of permanent magnets with azimuthal symmetry. Rev Mex Fis E 59:8–17
Chertok B, Langer R (2018) Circulating magnetic microbubbles for localized real-time control of drug delivery by ultrasonography-guided magnetic targeting and ultrasound. Theranostics. https://doi.org/10.7150/thno.20781
Chung M, Bernheim A, Mei X et al (2020) CT imaging features of 2019 novel coronavirus (2019-NCoV). Radiology 295:202–207. https://doi.org/10.1148/radiol.2020200230
Decuzzi P, Ferrari M (2006) The adhesive strength of non-spherical particles mediated by specific interactions. Biomaterials. https://doi.org/10.1016/j.biomaterials.2006.05.024
Ebrahimi S, Shamloo A, Alishiri M et al (2021a) Targeted pulmonary drug delivery in coronavirus disease (COVID-19) therapy: a patient-specific in silico study based on magnetic nanoparticles-coated microcarriers adhesion. Int J Pharm 609:121133. https://doi.org/10.1016/j.ijpharm.2021.121133
Ebrahimi S, Vatani P, Amani A, Shamloo A (2021b) Drug delivery performance of nanocarriers based on adhesion and interaction for abdominal aortic aneurysm treatment. Int J Pharm 594:120153. https://doi.org/10.1016/j.ijpharm.2020.120153
Furlani EP (2006) Analysis of particle transport in a magnetophoretic microsystem. J Appl Phys 99:2. https://doi.org/10.1063/1.2164531
Ghodousi M, Shahgholi M, Payganeh G (2018) Analysis of nonlinear vibrations and stability of rotating asymmetrical nano-shafts incorporating surface energy effects. Contin Mech Thermodyn 30:783–803. https://doi.org/10.1007/s00161-018-0640-z
Goldman AJ, Cox RG, Brenner H (1967) Slow viscous motion of a sphere parallel to a plane wall-II Couette flow. Chem Eng Sci. https://doi.org/10.1016/0009-2509(67)80048-4
Gori F, Boghi A (2011) Two new differential equations of turbulent dissipation rate and apparent viscosity for non-newtonian fluids. Int Commun Heat Mass Transf. https://doi.org/10.1016/j.icheatmasstransfer.2011.03.003
Hasan SS, Capstick T, Ahmed R et al (2020) Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis. Expert Rev Respir Med 14:1149–1163. https://doi.org/10.1080/17476348.2020.1804365
Hochhaus G (2004) New developments in corticosteroids. Proc Am Thorac Soc 1(3):269–274
Horcajada P, Serre C, Vallet-Regí M et al (2006) Metal-organic frameworks as efficient materials for drug delivery. Angew Chemie 118(36):6120–6124. https://doi.org/10.1002/anie.200601878
Islam MS, Saha SC, Sauret E et al (2017) Pulmonary aerosol transport and deposition analysis in upper 17 generations of the human respiratory tract. J Aerosol Sci 108:29–43. https://doi.org/10.1016/j.jaerosci.2017.03.004
Kavanagh O, Marie Healy A, Dayton F et al (2020) Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19. Med Hypotheses 143:110110
Kelly M, Yeoh GH, Timchenko V (2015) On computational fluid dynamics study of magnetic drug targeting. J Comput Multiph Flows 7:43–56. https://doi.org/10.1260/1757-482X.7.1.43
Kenjereš S (2008) Numerical analysis of blood flow in realistic arteries subjected to strong non-uniform magnetic fields. Int J Heat Fluid Flow 29:752–792. https://doi.org/10.1016/j.ijheatfluidflow.2008.02.014
Kim MM, Zydney AL (2004) Effect of electrostatic, hydrodynamic, and Brownian forces on particle trajectories and sieving in normal flow filtration. J Colloid Interface Sci 269:425–431. https://doi.org/10.1016/j.jcis.2003.08.004
Kim CS, Iglesias AJ, Garcia L (1989) Deposition of inhaled particles in bifurcating airway models: II. expiratory deposition. J Aerosol Med Depos Clear Eff Lung 2:15–27. https://doi.org/10.1089/jam.1989.2.15
Kumar N, Hassan S, Yoon J (2013) Optimized targeting of magnetic nano particles for drug delivery system. In: 2013 IEEE/ASME International Conference on Advanced Intelligent Mechatronics: Mechatronics for Human Wellbeing, AIM 2013
Lambert AR, O’Shaughnessy PT, Tawhai MH et al (2011) Regional deposition of particles in an image-based airway model: Large-eddy simulation and left-right lung ventilation asymmetry. Aerosol Sci Technol 45:11–25. https://doi.org/10.1080/02786826.2010.517578
Lepper PM, Muellenbach RM (2020) Mechanical ventilation in early COVID-19 ARDS. EClinicalMedicine 28
Li A, Ahmadi G (1992) Dispersion and deposition of spherical particles from point sources in a turbulent channel flow. Aerosol Sci Technol 16:209–226. https://doi.org/10.1080/02786829208959550
Liu F, Ji C, Luo J et al (2020) Clinical characteristics and corticosteroids application of different clinical types in patients with corona virus disease 2019. Sci Rep 10:13689. https://doi.org/10.1038/s41598-020-70387-2
Lunnoo T, Puangmali T (2015) Capture efficiency of biocompatible magnetic nanoparticles in arterial flow: a computer simulation for magnetic drug targeting. Nanoscale Res Lett 10:1–11. https://doi.org/10.1186/s11671-015-1127-5
Martinez RC, Roshchenko A, Minev P, Finlay WH (2013) Simulation of enhanced deposition due to magnetic field alignment of ellipsoidal particles in a lung bifurcation. J Aerosol Med Pulm Drug Deliv 26:31–40. https://doi.org/10.1089/jamp.2011.0921
Meng Z, Huang H, Huang D et al (2021) Functional metal–organic framework-based nanocarriers for accurate magnetic resonance imaging and effective eradication of breast tumor and lung metastasis. J Colloid Interface Sci 581:31–43. https://doi.org/10.1016/j.jcis.2020.07.072
Mody NA, King MR (2007) Influence of Brownian motion on blood platelet flow behavior and adhesive dynamics near a planar wall. Langmuir 23:6321–6328. https://doi.org/10.1021/la0701475
Nilsestuen JO, Hargett KD (2005) Using ventilator graphics to identify patient-ventilator asynchrony. Respir Care 50:202–232
Ostrovski Y, Dorfman S, Mezhericher M et al (2019) Targeted drug delivery to upper airways using a pulsed aerosol bolus and inhaled volume tracking method. Flow, Turbul Combust 102:73–87. https://doi.org/10.1007/s10494-018-9927-1
Owen J, Rademeyer P, Chung D et al (2015) Magnetic targeting of microbubbles against physiologically relevant flow conditions. Interface Focus 5:20150001. https://doi.org/10.1098/rsfs.2015.0001
Patwa A, Shah A (2015) Anatomy and physiology of respiratory system relevant to anaesthesia. Indian J Anaesth 59:533
Poh W, Ab Rahman N, Ostrovski Y et al (2019) Active pulmonary targeting against tuberculosis (TB) via triple-encapsulation of Q203, bedaquiline and superparamagnetic iron oxides (SPIOs) in nanoparticle aggregates. Drug Deliv. https://doi.org/10.1080/10717544.2019.1676841
Pourmehran O, Rahimi-Gorji M, Gorji-Bandpy M, Gorji TB (2015) Simulation of magnetic drug targeting through tracheobronchial airways in the presence of an external non-uniform magnetic field using Lagrangian magnetic particle tracking. J Magn Magn Mater. https://doi.org/10.1016/j.jmmm.2015.05.086
Price DN, Stromberg LR, Kunda NK, Muttil P (2017) In vivo pulmonary delivery and magnetic-targeting of dry powder nano-in-microparticles. Mol Pharm. https://doi.org/10.1021/acs.molpharmaceut.7b00532
Pyrhönen J, Jokinen T, Hrabovcová V (2013) Design of Rotating Electrical Machines
Rostami M, Aghajanzadeh M, Zamani M et al (2018) Sono-chemical synthesis and characterization of Fe3O4@mTiO2-GO nanocarriers for dual-targeted colon drug delivery. Res Chem Intermed. https://doi.org/10.1007/s11164-017-3204-0
Saadat M, Manshadi MKD, Mohammadi M et al (2020) Magnetic particle targeting for diagnosis and therapy of lung cancers. J Control Release 328:776–791. https://doi.org/10.1016/j.jconrel.2020.09.017
Sabz M, Kamali R, Ahmadizade S (2019) Numerical simulation of magnetic drug targeting to a tumor in the simplified model of the human lung. Comput Methods Programs Biomed 172:11–24. https://doi.org/10.1016/j.cmpb.2019.02.001
Shamloo A, Ebrahimi S, Amani A, Fallah F (2020) Targeted drug delivery of microbubble to arrest abdominal aortic aneurysm development: a simulation study towards optimized microbubble design. Sci Rep. https://doi.org/10.1038/s41598-020-62410-3
Shamloo A, Boroumand A, Ebrahimi S et al (2022a) Modeling of an ultrasound system in targeted drug delivery to abdominal aortic aneurysm: a patient-specificin silico study based on ligand-receptor binding. IEEE Trans Ultrason Ferroelectr Freq Control. https://doi.org/10.1109/TUFFC.2021.3138868
Shamloo A, Ebrahimi S, Ghorbani G, Alishiri M (2022b) Targeted drug delivery of magnetic microbubble for abdominal aortic aneurysm: an in silico study. Biomech Model Mechanobiol. https://doi.org/10.1007/s10237-022-01559-4
Simon-Yarza T, Mielcarek A, Couvreur P, Serre C (2018) Nanoparticles of metal-organic frameworks: on the road to in vivo efficacy in biomedicine. Adv Mater 30:1707365
Sohrabi S, Zheng J, Finol EA, Liu Y (2014) Numerical simulation of particle transport and deposition in the pulmonary vasculature. J Biomech Eng 136:121010. https://doi.org/10.1115/1.4028800
Tan J, Thomas A, Liu Y (2012) Influence of red blood cells on nanoparticle targeted delivery in microcirculation. Soft Matter 8:1934–1946. https://doi.org/10.1039/c2sm06391c
Tzotzos SJ, Fischer B, Fischer H, Zeitlinger M (2020) Incidence of ARDS and outcomes in hospitalized patients with COVID-19: A global literature survey. Crit Care 24:1–4
Verma NK, Crosbie-Staunton K, Satti A et al (2013) Magnetic core-shell nanoparticles for drug delivery by nebulization. J Nanobiotechnol. https://doi.org/10.1186/1477-3155-11-1
Wang M, Li L, Zhang X et al (2018) Magnetic resveratrol liposomes as a new theranostic platform for magnetic resonance imaging guided parkinson’s disease targeting therapy. ACS Sustain Chem Eng. https://doi.org/10.1021/acssuschemeng.8b04507
Wu MX, Yang YW (2017) Metal-organic framework (MOF)-based drug/cargo delivery and cancer therapy. Adv Mater 29:1606134
Zhang H, Ma Y, Sun X-L (2010) Recent developments in carbohydrate-decorated targeted drug/gene delivery. Med Res Rev 30:270–289. https://doi.org/10.1002/med.20171
Zhao HX, Zou Q, Sun SK et al (2016) Theranostic metal-organic framework core-shell composites for magnetic resonance imaging and drug delivery. Chem Sci. https://doi.org/10.1039/c6sc01359g
Zheng Y, Zhao Y, Bai M et al (2022) Metal-organic frameworks as a therapeutic strategy for lung diseases. J Mater Chem B 10:5666–5695
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HR initiated the idea, designed the simulations, analyzed the data, ran the simulations, wrote the paper, and revised the paper; AF designed the simulations, analyzed the data, wrote the paper, and revised the paper; MR ran the simulations and wrote the paper.
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Ranjbar, H., Farajollahi, A. & Rostami, M. Targeted drug delivery in pulmonary therapy based on adhesion and transmission of nanocarriers designed with a metal–organic framework. Biomech Model Mechanobiol 22, 2153–2170 (2023). https://doi.org/10.1007/s10237-023-01756-9
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DOI: https://doi.org/10.1007/s10237-023-01756-9