TISSUE PENETRABILITY OF NANOPARTICLES LOADED WITH RHODAMINE B FLUORESCENT MARKER USING A TRIMODAL ADMINISTRATION APPROACH

Authors

  • Roxana Florentina SUFARU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • C.I. STAN “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Catalina Anisoara PEPTU “Gheorghe Asachi” Technical University of Iasi, Romania
  • L.C. GAVRIL “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • D.A. CHIRAN “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • D.V. CRAUCIUC “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Ruxandra VATAVU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Anca SAVA “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Abstract

Nanoparticles can incorporate a drug, as means of protection towards body physiological barriers, and release it in a controlled manner in a targeted tissue. This study aims to investigate the absorption of nanoparticles, loaded with Rhodamine B fluorescent marker, in different organs, by trimodal administration: endogastric, intraperitoneal and intravenous, for three days. Materials and methods: The extent of absorption of Rhodamine B dye in liver, gums, kidneys, ovaries and testes was determined using fluorescence microscopy in frozen sections on harvested organs from rats. The experiment required 24 adult male rats that were divided into four groups of six rats each. Group A was designated as the control group, while the other three groups, B, C and D, respectively, received Rhodamine-loaded nanoparticles for three consecutive days, at a dose of 0.05 mg/kg body weight. The methods of administration for the three study groups were as follows: endogastric for group B, intraperitoneal for group C, and injection into the tail vein for group D. On the fourth day the animals were sacrificed, and organs were removed and preserved in paraformaldehyde containers, to be studied under an immunofluorescence microscope. A four-level scale was used to evaluate organ penetrability for the given nanosystems. Results: Intraperitoneally administrated nanocarriers, marked with Rhodamine B, showed the highest degree of absorption in liver in 83.3% of the rats, compared to the endogastric route, where the same level of absorption was in only 33.3% of the animals (p=0.050). Regarding the two parenteral tested pathways, the absorption level presented statistical differences among the intraperitoneal vs. intravenous groups, in gum (p=0.011), heart (p=0.004), kidney (p=0.050) and testicle (p=0.011), whereas there was no statistical difference in liver tissue (p=0.250). Conclusions: The parenteral routes of administration had statistically significant higher organ penetrability, compared to the endogastric tube. Amongst the organs, liver had the most absorptive behavior due to its intrinsic metabolizing role, and there was no major difference between the intraperitoneal vs. intravenous injections.

Author Biographies

  • Roxana Florentina SUFARU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Ph.D. Student, Doctoral School,
    Department of Morpho-Functional Sciences (I)

  • C.I. STAN, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Department of Morpho-Functional Sciences (I)

  • Catalina Anisoara PEPTU, “Gheorghe Asachi” Technical University of Iasi, Romania

    Faculty of Chemical Engineering and Environmental Protection
    Department of Natural and Synthetic Polymers

  • L.C. GAVRIL, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Department of Morpho-Functional Sciences (I)

  • D.A. CHIRAN, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Department of Morpho-Functional Sciences (I)

  • D.V. CRAUCIUC, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Department of Morpho-Functional Sciences (I)

  • Ruxandra VATAVU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Ph.D. Student, Doctoral School,
    Department of Morpho-Functional Sciences (I)

  • Anca SAVA, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Department of Morpho-Functional Sciences (I)
    “Prof. Dr. N. Oblu” Emergency Clinical Hospital, Iasi, Romania

References

1. Tinkle S, McNeil SE, Mühlebach S, et al. Nanomedicines: addressing the scientific and regulatory gap. Ann N Y Acad Sci 2014; 1313: 35-56 / doi:10.1111/nyas.12403.
2. Bleeker EA, de Jong WH, Geertsma RE, et al. Considerations on the EU definition of a nanomaterial: science to support policy making. Regul Toxicol Pharmacol. 2013;65(1):119-125/ doi: 10.1016/j.yrtph.2012.11.007.
3. Soares S, Sousa J, Pais A, Vitorino C. Nanomedicine: Principles, Properties, and Regulatory Is-sues. Front Chem 2018; 6: 360 / doi:10.3389/fchem.2018.00360.
4. Pita R, Ehmann F, Papaluca M. Nanomedicines in the EU-Regulatory Overview. AAPS J. 2016; 18(6): 1576-1582 / doi:10.1208/s12248-016-9967-1.
5. Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles [published correction appears in Environ Health Perspect. 2010; 118(9): A380]. Environ Health Perspect. 2005; 113(7): 823-839 / doi: 10.1289/ ehp.7339.
6. Kim BY, Rutka JT, Chan WC. Nanomedicine. N Engl J Med 2010; 363(25): 2434-2443/ doi: 10.1056/NEJMra0912273.
7. Albanese A, Tang PS, Chan WC. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng 2012; 14: 1-16 / doi: 10.1146/annurev-bioeng-071811-150124.
8. European Food Safety Authority. Opinion of the Scientific Panel on food additives, flavorings, pro-cessing aids and materials in contact with food (AFC) to review the toxicology of a number of dyes il-legally present in food in the EU. EFSA Journal. 2005; 3(9):263-271/ doi: 10.2903/j.efsa.2005.263.
9. Mizuno N, Fujiwara A, Morita E. Effect of dyes on the photodecomposition of pyridoxine and pyri-doxamine. J Pharm Pharmacol 1981; 33(6): 373-376 / doi: 10.1111/j.2042-7158. 1981.tb13807.x.
10. Wang H, Lu L, Zhu S, Li Y, Cai W. The phototoxicity of xanthene derivatives against Escherichia coli, Staphylococcus aureus, and Saccharomyces cerevisiae. Curr Microbiol 2006; 52(1):1-5 / doi: 10.1007/s00284-005-0040-z.
11. Shea CR, Chen N, Wimberly J, Hasan T. Rhodamine dyes as potential agents for photo-chemotherapy of cancer in human bladder carcinoma cells. Cancer Res. 1989; 49(14): 3961-3965.
12. Mahdi C, Afyan Pratama C, Pratiwi H. Preventive study garlic extract water (Allium Sativum) toward SGPT, SGOT, and the description of liver histopathology on rat (Rattus Norvegicus), which were ex-posed by rhodamine B. Materials Science and Engineering Conference Series 2019; 546(6): 062015 / doi: 10.1088/1757-899X/546/6/062015.
13. Wildner G. Are rats more human than mice? Immunobiology 2019; 224(1): 172-176 / doi: 10.1016/ j.imbio.2018.09.002.
14. Blais EM, Rawls KD, Dougherty BV, et al. Reconciled rat and human metabolic networks for com-parative toxicogenomics and biomarker predictions. Nat Commun 2017; 8: 14250 / doi: 10.1038/ncomms14250.
15. Ciobanu BC, Cadinoiu AN, Popa M, Desbrières J, Peptu CA. Modulated release from liposomes entrapped in chitosan/gelatin hydrogels. Mater Sci Eng C Mater Biol Appl 2014; 43: 383-391 / doi: 10.1016/j.msec.2014.07.036.
16. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 2005; 4(2): 145-160 / doi: 10.1038/nrd1632.
17. Sufaru RF, Radulescu AM, Vatavu R, et al. Tissue penetrability as a function of nanoparticle delivery mode. J Med Med Sci 2023: 14(2): 1-4.
18. Shah S, Dhawan V, Holm R, Nagarsenker MS, Perrie Y. Liposomes: Advancements and innovation in the manufacturing process. Adv Drug Deliv Rev 2020; 154-155: 102-122/ doi: 10.1016/ j.addr.2020.07.002.
19. Das S, Chaudhury A. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech 2011; 12(1): 62-76 / doi: 10.1208/s12249-010-9563-0.
20. Mehnert W, Mäder K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev 2001; 47(2-3): 165-196 / doi: 10.1016/s0169-409x (01) 00 105-3.
21. Parker SE, Davey PG. Pharmacoeconomics of intravenous drug administration. Pharmaco-economics 1992; 1(2): 103-115 / doi: 10.2165/00019053-199 201 020-00007.
22. Chenthamara D, Subramaniam S, Ramakrishnan SG, et al. Therapeutic efficacy of nanoparticles and routes of administration. Biomater Res 2019; 23: 20 / doi: 10.1186/s40824-019-0166-x.
23. Kim C, Kim IH, Kim SI, et al. Comparison of the intraperitoneal, retroorbital and per oral routes for F-18 FDG administration as effective alternatives to intravenous administration in mouse tumor models using small animal PET/CT studies. Nucl Med Mol Imaging 2011; 45(3): 169-176 / doi: 10.1007/ s13139-011-0087-7.
24. Dias ML, Carvalho JP, Rodrigues DG, Graziani SR, Maranhão RC. Pharmacokinetics and tumor uptake of a derivatized form of paclitaxel associated to a cholesterol-rich nanoemulsion (LDE) in pa-tients with gynecologic cancers. Cancer Chemother Pharmacol 2007; 59(1): 105-111 / doi: 10.1007/s00280-006-0252-3
25. Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery a review of the state of the art. Eur J Pharm Biopharm 2000; 50(1): 161-177 / doi: 10.1016/ s0939-6411(00)00087-4.
26. Islam MM, Chakraborty M, Pandya P, Masum A, Gupta N, Mukhopadhyay S. Binding of DNA with rhodamine B: spectroscopic and molecular modeling studies. Dyes Pigm 2013; 99: 412-422 / doi: 10.1016/j.dyepig.2013.05.028.
27. Kim HN, Lee MH, Kim HJ, Kim JS, Yoon J. A new trend in rhodamine-based chemosensory: appli-cation of Spiro lactam ring-opening to sensing ions. Chem Soc Rev. 2008; 37(8): 1465-1472 / doi: 10.1039/b802497a.
28. Wang D, Wang Z, Li Y, et al. A single rhodamine Spiro lactam probe for localization and pH moni-toring of mitochondrion/lysosome in living cells. New J Chem 2018; 42: 11102-11108 / doi: 10.1039/C8NJ01895B.
29. Wang L, Chan JY, Rêgo JV, et al. Rhodamine B-conjugated encrypted vipericidin nonapeptide is a potent toxin to zebrafish and associated with in vitro cytotoxicity. Biochim Biophys Acta 2015; 1850(6): 1253-1260 / doi: 10.1016/j.bbagen.2015.02.013.
30. Mizuno N, Fujiwara A, Morita E. Effect of dyes on the photodecomposition of pyridoxine and pyri-doxamine. J Pharm Pharmacol 1981; 33(6): 373-376 / doi: 10.1111/j.2042-7158. 1981. Tb 13807.x.
31. Milvy P, Kay K. Mutagenicity of u9 major graphic arts and printing dyes. J Toxicol Environ Health 1978; 4(1): 31-36 / doi: 10.1080/15287397809529641.
32. Smart, P.L. A review of the toxicity of twelve fluorescent dyes used for water tracing. NSS Bull 1984; 46: 21-33.
33. Elliott GS, Mason RW, Edwards IR. Studies on the pharmacokinetics and mutagenic potential of rhodamine B. J Toxicol Clin Toxicol 1990; 28(1): 45-59 / doi: 10.3109/ 1556365 9008993475.
34. Behrens H, Beims U, Dieter H, et al. Toxicological and ecotoxicological assessment of water tracers. Hydrogeology Journal 2001; 9: 325 / doi: 10.1007/s100400100126.
35. Hoenke S, Serbian I, Deigner HP, Csuk R. Mitocanic Di- and Triterpenoid Rhodamine B Conju-gates. Molecules 2020; 25(22): 5443/ doi: 10.3390/molecules25225443.
36. Mammana S, Gugliandolo A, Cavalli E, et al. Human gingival mesenchymal stem cells pretreated with vesicular moringin nanostructures as a new therapeutic approach in a mouse model of spinal cord injury. J Tissue Eng Regen Med 2019; 13(7): 1109-1121 / doi: 10.1002/ term.2857.
37. Chaudhry S, Emond J, Griesemer A. Immune Cell Trafficking to the Liver. Transplantation 2019; 103(7): 1323-1337 / doi: 10.1097/TP.0000000000002690.
38. Al-Agha OM, Axiotis CA. An in-depth look at Leydig cell tumor of the testis. Arch Pathol Lab Med 2007; 131(2): 311-317 / doi:10.5858/2007-131-311-AILALC.
39. Johnson BJ, Mitchell SN, Paton CJ, et al. Use of rhodamine B to mark the body and seminal fluid of male Aedes aegypti for mark-release-recapture experiments and estimating efficacy of sterile male re-leases. PLoS Negl Trop Dis 2017; 11(9): e0005902 / doi: 10.1371/journal.pntd. 0005902.
40. Battula H, Bommi S, Bobde Y, et al. Distinct rhodamine B derivatives exhibiting dual effect of anti-cancer activity and fluorescence property. J Photochem Photobiol 2021; 6: 100026 / doi: 10.1016/ j.jpap.2021.100026.

Additional Files

Published

2023-12-21

Issue

Vol. 127 No. 4 (2023): The Medical-Surgical Journal

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BASIC SCIENCES

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