Skip to main content
Log in

Senescence and the Impact on Biodistribution of Different Nanosystems: the Discrepancy on Tissue Deposition of Graphene Quantum Dots, Polycaprolactone Nanoparticle and Magnetic Mesoporous Silica Nanoparticles in Young and Elder Animals

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purposes

Senescence is an inevitable and irreversible process, which may lead to loss in muscle and bone density, decline in brain volume and loss in renal clearance. Although aging is a well-known process, few studies on the consumption of nanodrugs by elderly people were performed.

Methods

We evaluated three different nanosystems: i) carbon based nanosystem (Graphene Quantum Dots, GQD), ii) polymeric nanoparticles and mesoporous silica (magnetic core mesoporous silica, MMSN). In previous studies, our group has already characterized GQD and MMSN nanoparticles by dynamic light scattering analysis, atomic force microscopy, transmission electron microscopy, X-ray diffraction, Raman analysis, fluorescence and absorbance. The polymeric nanoparticle has been characterized by AFM and DLS. All the nanosystems were radiolabeled with 99 m-Tc by. The in vivo biodistribution/tissue deposition analysis evaluation was done using elder (PN270) and young (PN90) mice injected with radioactive nanosystems.

Results

The nanosystems used in this study were well-formed as the radiolabeling processes were stable. Biodistribution analysis showed that there is a decrease in the uptake of the nanoparticles in elder mice when compared to young mice, showing that is necessary to increase the initial dose in elder people to achieve the same concentration when compared to young animals.

Conclusion

The discrepancy on tissue distribution of nanosystems between young and elder individuals must be monitored, as the therapeutic effect will be different in the groups. Noteworthy, this data is an alarm that some specific conditions must be evaluated before commercialization of nano-drugs.

Changes between younger and elderly individuals are undoubtedly, especially in drug tissue deposition, biodistribution and pharmacokinetics. The same thought should be applied to nanoparticles. A comprehensive analysis on how age discrepancy change the biological behavior of nanoparticles has been performed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

DNA:

Deoxyribonucleic acid

IL-6:

Interleukin-6

TNF-alpha:

Tumor Necrosis factor-alpha

NPs:

Nanoparticles

PCL:

Polycaprolactone (PCL)

PDI:

Polydispersity index (PDI)

DLS:

Dynamic light scattering (DLS)

99mTc:

99mTechentium

MMSN:

Magnetic core mesoporous silica

GQDs:

Graphene quantum dots

PN90:

Postnatal day 90 (young animals)

PN270:

Postnatal day 270 (elder animals)

AFM:

Atomic Force Microscopy

References

  1. Liu Y, Gao W, Koellmann C, Le Clerc S, Huls A, Li B, et al. Genome-wide scan identified genetic variants associated with skin aging in a Chinese female population. J Dermatol Sci. 2019. https://doi.org/10.1016/j.jdermsci.2019.08.010.

  2. Thomas N, Gurvich C, Kulkarni J. Sex differences in aging and associated biomarkers. Adv Exp Med Biol. 2019;1178:57–76. https://doi.org/10.1007/978-3-030-25650-0_4.

    Article  CAS  PubMed  Google Scholar 

  3. Shavlakadze T, Morris M, Fang J, Wang SX, Zhu J, Zhou W, et al. Age-related gene expression signature in rats demonstrate early, late, and linear transcriptional changes from multiple tissues. Cell Rep. 2019;28:3263–3273.e3. https://doi.org/10.1016/j.celrep.2019.08.043.

    Article  CAS  PubMed  Google Scholar 

  4. Dodig S, Čepelak I, Pavić I. Hallmarks of senescence and aging. Biochem medica. 2019;29:30501. https://doi.org/10.11613/bm.2019.030501.

    Article  Google Scholar 

  5. Victorelli S, Passos JF. Telomeres and cell senescence. EBioMedicine. 2017;21:14–20. https://doi.org/10.1016/j.ebiom.2017.03.027.

    Article  PubMed  PubMed Central  Google Scholar 

  6. M. Chiriaco, G. Georgiopoulos, E. Duranti, L. Antonioli, I. Puxeddu, M. Nannipieri, J. Rosada, C. Blandizzi, S. Taddei, A. Virdis, et al., Inflammation and vascular ageing: from telomeres to novel emerging mechanisms, high blood press. Cardiovasc. Prev. (2019) 321–329. https://doi.org/10.1007/s40292-019-00331-7.

  7. Pereira BI, Devine OP, Vukmanovic-Stejic M, Chambers ES, Subramanian P, Patel N, et al. Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition. Nat Commun. 2019;10:2387 https://doi.org/10.1038/s41467-019-10335-5.

    Article  Google Scholar 

  8. T. Tchkonia, J. L. Kirkland, JAMA , Aging, cell senescence, and chronic disease, (2018), 1319. https://doi.org/10.1001/jama.2018.12440.

  9. D. S. Cho, J. D. Doles, Skeletal muscle progenitor cell heterogeneity, Adv. Exp. Med. Biol. (2019)179–193. https://doi.org/10.1007/978-3-030-24108-7_9.

  10. K. Kounakis, N. Tavernarakis, The cytoskeleton as a modulator of aging and neurodegeneration. Adv Exp Med Biol. (2019), 227–245. https://doi.org/10.1007/978-3-030-25650-0_12.

  11. Forsberg A, Johnson W, Logie RH. Aging and feature-binding in visual working memory: the role of verbal rehearsal. Psychol Aging. 2019. https://doi.org/10.1037/pag0000391.

  12. B. Pan, H. Li, Y. Wang, M. Sun, H. Cai, J. Wang, Physical activity and the risk of frailty among community-dwelling healthy older adults. Medicine (Baltimore). (2019),, e16955. https://doi.org/10.1097/md.0000000000016955.

  13. M. Ogrodnik, H. Salmonowicz, V. N. Gladyshev, Integrating cellular senescence with the concept of damage accumulation in aging: Relevance for clearance of senescent cells., Aging Cell (2019) e12841. https://doi.org/10.1111/acel.12841.

  14. Bu H, Wedel S, Cavinato M, Jansen-Dürr P. MicroRNA regulation of oxidative stress-induced cellular senescence. Oxidative Med Cell Longev. 2017:1–17. https://doi.org/10.1155/2017/2398696.

  15. H. Song, M. Wei, N. Zhang, H. Li, X. Tan, Y. Zhang, W. Zheng, Enhanced permeability of blood–brain barrier and targeting function of brain via borneol-modified chemically solid lipid nanoparticle, Int. J. Nanomedicine (2018) 1869–1879. https://doi.org/10.2147/ijn.s161237.

  16. A. Alexander, M. Agrawal, A. Uddin, S. Siddique, A. M. Shehata, M. A. Shaker, S. Ata Ur Rahman, M. I. M. Abdul, M. A. Shaker, Recent expansions of novel strategies towards the drug targeting into the brain. Int. J. Nanomedicine (2019) 5895–5909. https://doi.org/10.2147/ijn.s210876

  17. Faustino C, Rijo P, Reis CP. Nanotechnological strategies for nerve growth factor delivery: therapeutic implications in Alzheimer’s disease. Pharmacol Res. 2017;120:68–87. https://doi.org/10.1016/j.phrs.2017.03.020.

    Article  CAS  PubMed  Google Scholar 

  18. Y. Xiao, D. Xu, H. Song, F. Shu, P. Wei, X. Yang, C. Zhong, X. Wang, W. E. Muller, Y. Zheng, et al., Cuprous oxide nanoparticles reduces hypertrophic scarring by inducing fibroblast apoptosis. Int. J. Nanomedicine (2019) 5989–6000. https://doi.org/10.2147/ijn.s196794.

  19. Choi YH, Han H-K. Nanomedicines: current status and future perspectives in aspect of drug delivery and pharmacokinetics. J Pharm Investig. 2018;48:43–60. https://doi.org/10.1007/s40005-017-0370-4.

    Article  CAS  PubMed  Google Scholar 

  20. R.-M. F, S. N, A. N, J. N. Gold-Curcumin Nanostructure in Photothermal Therapy on Breast Cancer Cell Line: 650 and 808 nm Diode Lasers as Light Sources.Biomed. Phys. Eng. (2019). https://doi.org/10.31661/jbpe.v0i0.906.

  21. Dhas N, Ige P, Kudarha R. Design, optimization and in-vitro study of folic acid conjugated-chitosan functionalized plga nanoparticle for delivery of bicalutamide in prostate cancer. Power Technol. 2015;283:234–45. https://doi.org/10.1016/j.powtec.2015.04.053.

    Article  CAS  Google Scholar 

  22. Jain A, Jain A, Garg NK, Tyagi RK, Singh B, Katare OP, et al. Surface engineered polymeric nanocarriers mediate the delivery of transferrin–methotrexate conjugates for an improved understanding of brain cancer. Acta Biomater. 2015;24:140–51. https://doi.org/10.1016/j.actbio.2015.06.027.

    Article  CAS  PubMed  Google Scholar 

  23. M. Ben Haddada, D. Koshel, Z. Yang, W. Fu, J. Spadavecchia, S. Pesnel, A.-L. Morel, Proof of concept of plasmonic thermal destruction of surface cancers by gold nanoparticles obtained by green chemistry. Colloids Surf. B. Biointerfaces (2019) 110496. https://doi.org/10.1016/j.colsurfb.2019.110496

  24. R. Maity, M. Chatterjee, A. Banerjee, A. Das, R. Mishra, S. Mazumder, N. Chanda, Gold nanoparticle-assisted enhancement in the anti-cancer properties of theaflavin against human ovarian cancer cells. Mater. Sci. Eng. C. Mater. Biol. Appl. (2019) 109909. https://doi.org/10.1016/j.msec.2019.109909

  25. L.-X. Gai, W.-Q. Wang, X. Wu, X.-J. Su, F.-C. Yang, J. NIR absorbing reduced graphene oxide for photothermal radiotherapy for treatment of esophageal cancer. Photochem. Photobiol. B. (2019) 188–193. https://doi.org/10.1016/j.jphotobiol.2019.03.014.

  26. Zheng Z, Huang L, Yan L, Yuan F, Wang L, Wang K, et al. Polyaniline functionalized Graphene Nanoelectrodes for the regeneration of PC12 cells via electrical stimulation. Int J Mol Sci. 2019;2013. https://doi.org/10.3390/ijms20082013.

  27. Fan C, Kong F, Shetti D, Zhang B, Yang Y, Wei K. Resveratrol loaded oxidized mesoporous carbon nanoparticles: a promising tool to treat triple negative breast cancer. Biochem Biophys Res Commun. 2019. https://doi.org/10.1016/j.bbrc.2019.09.016.

  28. R. Kamakura, M. Kovalainen, J. Riikonen, T. Nissinen, G. Shere Raza, J. Walkowiak, V.-P. Lehto, K.-H. Herzig. Inorganic mesoporous particles for controlled α-linolenic acid delivery to stimulate GLP-1 secretion in vitro, Eur. J. Pharm. Biopharm. (2019) 132–138, https://doi.org/10.1016/j.ejpb.2019.09.009.

  29. Y.-C. Lin, C.-F. Lin, A. Alalaiwe, P.-W. Wang, Y.-P. Fang, J.-Y. Fang, UV filter entrapment in mesoporous silica hydrogel for skin protection against UVA with minimization of percutaneous absorption. Eur. J. Pharm. Sci. (2018) 185–194. https://doi.org/10.1016/j.ejps.2018.07.013.

  30. Y. He, S. Liang, M. Long, H. XuMesoporous silica nanoparticles as potential carriers for enhanced drug solubility of paclitaxel. Mater Sci Eng C, 78 (2017), pp. 12–17.

  31. Portilho FL, Helal Neto E, Cabezas SS, Pinto SR, Dos Santos SN, Pozzo L, et al. Magnetic core mesoporous silica nanoparticles doped with dacarbazine and labelled with 99mTc for early and differential detection of metastatic melanoma by single photon emission computed tomography. Nanomedicine, And Biotechnology: Artificial Cells; 2018. p. 1080–7. https://doi.org/10.1080/21691401.2018.1443941.

    Book  Google Scholar 

  32. de Menezes FD, Dos Reis SRR, Pinto SR, Portilho FL, do Vale Chaves E Mello F, Helal-Neto E, da Silva de Barros AO et al. Graphene quantum dots unraveling: green synthesis, characterization, radiolabeling with 99mTc, in vivo behavior and mutagenicity Materials Science and Engineering. (2019) 102, p.405–414. https://doi.org/10.1016/j.msec.2019.04.058.

  33. Saez, V, De Menezes FD, Dos Santos CC, Alencar, LMR, Ricci-Junior E, Mansur CRE, Santos-Oliveira R. Graphene quantum dots nanoparticles changed the rheological properties of hydrophilic gels (carbopol). Journal of Molecular Liquids. (2019) 110949. https://doi.org/10.1016/j.molliq.2019.110949

  34. Dos Santos, SN, Dos Reis SR, Pires LP, Helal-Neto E, Sancenon F, Barja-Fidalgo, TC, De Mattos RM et al.. Avoiding the mononuclear phagocyte system using human albumin for mesoporous silica nanoparticle system. Microporous And Mesoporous Materials. (2017) 181–189. https://doi.org/10.1016/j.micromeso.2017.06.005.

  35. Rosa TG, Dos Santos SN, de Jesus Andreoli Pinto T, Ghisleni DDM, Barja-Fidalgo TC, Ricci-Junior E, Al-Qahtani M, Kozempel J, Bernardes ES, Santos-Oliveira R. Microradiopharmaceutical for Metastatic Melanoma. Pharmaceutical Research. (2017). 2922–2930. https://doi.org/10.1007/s11095-017-2275-3.

  36. Fatemika H, Seyedabadi M, Karimi Z, Tanha K, Assadi M, Tanha K. Comparison of 99mTc-DMSA renal scintigraphy with biochemical and histopathological findings in animal models of acute kidney injury. Mol Cell Biochem. 2017;434(1–2):163–9. https://doi.org/10.1007/s11010-017-3046-5

    Article  CAS  Google Scholar 

  37. Rodrigues VST, Moura EG, Bernardino DN, Carvalho JC, Soares PN, Peixoto TC, et al. Supplementation of suckling rats with cow's milk induces hyperphagia and higher visceral adiposity in females at adulthood, but not in males. J Nutr Biochem. 2018;55:89–103. https://doi.org/10.1016/j.jnutbio.2017.12.001.

    Article  CAS  PubMed  Google Scholar 

  38. SJ Jackson, N Andrews , D Ball , I Bellantuono, J. Gray, L. Hachoumi, A. Holmes, J. Latcham, A. Petrie, P. Potter, A. Rice, A. Ritchie, K. Chapman. Does age matter? The impact of rodent age on study outcomes. Lab Anim. (2017) Apr;51(2):160–169.

  39. E. Lindsay, Pappas, TR. Nagy. The translation of age-related body composition findings from rodents to humans. Eur J Clin Nutr. (2019) Feb;73(2):172–178.

  40. Adams DJ. The valley of death in anticancer drug development: a reassessment. Trends Pharmacol Sci. 2012;33:173–80.

    Article  CAS  Google Scholar 

  41. A. Talevi, CL Bellera, M Di Ianni, M Gantner, LE Bruno- Blanch and EA Castro. CNS drug development – lost in translation? Mini Rev Med Chem. (2012) Sep 1;12(10):959–70.

  42. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8:e1000412.

    Article  Google Scholar 

  43. Landis SC, Amara SG, Asadullah K. A call for transparent reporting to optimize the predictive value of preclinical research. Nature. 2012;490:187.

    Article  CAS  Google Scholar 

  44. Koff RS, Garvey AJ, Burney SW, Bell B. Absence of an age effect on sulfobromophtalein retention in healthy men. Gastroenterology. 1973;65:300–2.

    Article  CAS  Google Scholar 

  45. Kampmann JP, Sinding J, Moller-Jorgensen I. Effect of age on liver function. Geriatrics. 1975;30:91–5.

    CAS  PubMed  Google Scholar 

  46. Fu A. NK Sreekumaran. Age effect on fibrinogen and albumin synthesis in humans. Am J Phys. 1998;275.

  47. Mori K, Blackshear PE, Lobenhofer EK. Hepatic transcript levels for genes coding for enzymes associated with xenobiotic metabolism are altered with age. Toxicol Pathol. 2007;35:242–51.

    Article  CAS  Google Scholar 

  48. Pibiri M, Sulas P, Leoni VP. Global gene expression profile of normal and regenerating liver in young and old mice. Age (Dordr). 2015;37:9796.

    Article  Google Scholar 

  49. Castleden CM, George CF. The effect of ageing on the hepatic clearance of propranolol. Br J Clin Pharmacol. 1979;7:49–54.

    Article  CAS  Google Scholar 

  50. Greenblatt DJ, Harmatz JS, Shapiro L, Engelhardt N, Gouthro TA, Shader RI. Sensitivity to triazolam in the elderly. N Engl J Med. 1991;324:1691–8.

    Article  CAS  Google Scholar 

  51. Anantharaju A, Feller A, Chedid A. Aging liver. A review Gerontology. 2002;48:343–53.

    Article  CAS  Google Scholar 

  52. Robertson DR, Waller DG, Renwick AG, George CF. Age-related changes in the pharmacokinetics and pharmacodynamics of nifedipine. Br J Clin Pharmacol. 1988;25:297–305.

    Article  CAS  Google Scholar 

  53. Castleden CM, Kaye CM, Parsons RL. The effect of age on plasma levels of propranolol and practolol in man. Br J Clin Pharmacol. 1975;2:303–6.

    Article  CAS  Google Scholar 

  54. Davies RO, Gomez HJ, Irvin JD, Walker JF. An overview of the clinical pharmacology of enalapril. Br J Clin Pharmacol. 1984;18(Suppl 2):215S–29S.

    Article  Google Scholar 

  55. Todd PA, Fitton A. Perindopril A review of its pharmacological properties and therapeutic use. Drugs. 1991;42:90–114.

    Article  CAS  Google Scholar 

  56. Jr Fulop T, Worum I, Csongor J, Foris G, Leovey A. Body composition in elderly people. I. Determination of body composition by multiisotope method and the elimination kinetics of these isotopes in healthy elderly subjects. Gerontology. 1985;31:6–14.

    Article  Google Scholar 

  57. Redolfi A, Borgogelli E, Lodola E. Blood level of cimetidine in relation to age. Eur J Clin Pharmacol. 1979;15:257–61.

    Article  CAS  Google Scholar 

  58. Zeeh J, Platt D. The aging liver: structural and functional changes and their consequences for drug treatment in old age. Gerontology. 2002;48(3):121–7.

    Article  CAS  Google Scholar 

  59. Tateishi T, Fujimura A, Shiga T, Ohashi K, Ebihara A. Influence of aging on the oxidative and conjugative metabolism of propranolol. Int J Clin Pharmacol Res. 1995;15(3):95–101.

    CAS  PubMed  Google Scholar 

  60. Anantharaju A, Feller A, Chedid A. Aging liver. A review. Gerontology. 2002;48(6):343–53.

    Article  CAS  Google Scholar 

  61. Sun X, Yan X, Jacobson O, Sun W, Wang Z, Tong X, et al. Improved tumor uptake by optimizing liposome based RES blockade strategy. Theranostics. 2017;7(2):319.

    Article  CAS  Google Scholar 

  62. Tsoi KM, MacParland SA, Ma X-Z, Spetzler VN, Echeverri J, Ouyang B, et al. Mechanism of hard-nanomaterial clearance by the liver. Nature Materials. 2016;15:1212.

    Article  CAS  Google Scholar 

  63. SA MacParland, KM Tsoi, B Ouyang, XZ Ma, J Manuel, A Fawaz, MA Ostrowski, BA Alman, A Zilman, WC Chan, ID McGilvray, Phenotype determines nanoparticle uptake by human macrophages from liver and blood ACS Nano, (2017) 28;11(3), 2428.

  64. Dreyfuss D, Shader RI, Harmatz JS, Greenblatt DJ. Kinetics and dynamics of single doses of oxazepam in the elderly: implications of absorption rate. J Clin Psychiatry. 1986;47:511–4.

    CAS  PubMed  Google Scholar 

  65. Divoll M, Ameer B, Abernethy DR, Greenblatt DJ. Age does not alter acetaminophen absorption. J Am Geriatr Soc. 1982;30:240–4.

    Article  CAS  Google Scholar 

  66. Gainsborough N, Maskrey VL, Nelson ML, Keating J, Sherwood RA, Jackson SHD, et al. The association of age with gastric emptying. Age Ageing. 1993;22:37–40.

    Article  CAS  Google Scholar 

  67. Wynne H. Drug metabolism and ageing. J Br Menopause Soc. 2005;11(2):51–6.

    Article  Google Scholar 

  68. Blechman MB, Gelb AM. Aging and gastrointestinal physiology. Clin Geriatr Med. 1999;15:429–38.

    Article  CAS  Google Scholar 

  69. Klawans HL. Emerging strategies in Parkinson’s disease. Neurology. 1990;40(Suppl 3):1–76.

    Google Scholar 

  70. Rostami-Hodjegan A, Kroemer HK, Tucker GT. In vivo indices of enzyme activity. The effect of renal impairment on the assessment of CYP2D6 activity. Pharmacogenetics. 1999;9:277–86.

    Article  CAS  Google Scholar 

  71. Yuan R, Venitz J. Effect of chronic renal failure on the disposition of highly hepatically metabolized drugs. Int J Clin Pharmacol Ther. 2000;38:245–53.

    Article  CAS  Google Scholar 

  72. Pichette V, Leblond FA. Drug metabolism in chronic renal failure. Curr Drug Metab. 2003;4:91–103.

    Article  CAS  Google Scholar 

  73. Wynne HA, Cope LH, Mutch E, Rawlins MD, Woodhouse KW, James OF. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology. 1989;9:297–301.

    Article  CAS  Google Scholar 

  74. de Jesus FC, Helal-Neto E, Portilho FL, Rocha Pinto S, Sancenón F, Martínez-Máñez R, et al. Effect of obesity on biodistribution of nanoparticles. J Control Release. 2018 Jul 10;281:11–8. https://doi.org/10.1016/j.jconrel.2018.05.003.

    Article  CAS  Google Scholar 

  75. De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJ. Geertsma RE particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials. 2008 Apr;29(12):1912–9.

    Article  Google Scholar 

  76. Kattumuri V, Katti K, Bhaskaran S, Boote EJ, Casteel SW, Fent GM, et al. Gum arabic as a phytochemical construct for the stabilization of gold nanoparticles: in vivo pharmacokinetics and X-ray-contrast-imaging studies. Small. 2007 Feb;3(2):333–41.

    Article  CAS  Google Scholar 

  77. Mohamed Anwar K Abdelhalim and Bashir M Jarrar Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles. GNP Lipids Health Dis. 2011; 10: 163. https://doi.org/10.1186/1476-511X-10-163

  78. AA Mangoni and SH Jackson. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. (2004) Jan;57(1):6–14.

  79. S. Shaojun and K Ulrich. Age-Related Changes in Pharmacokinetics. Current Drug Metabolism, Volume 12, Number 7 (2011) pp. 601–610(10).

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ralph Santos-Oliveira.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 214 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

dos Reis, S.R.R., Pinto, S.R., de Menezes, F.D. et al. Senescence and the Impact on Biodistribution of Different Nanosystems: the Discrepancy on Tissue Deposition of Graphene Quantum Dots, Polycaprolactone Nanoparticle and Magnetic Mesoporous Silica Nanoparticles in Young and Elder Animals. Pharm Res 37, 40 (2020). https://doi.org/10.1007/s11095-019-2754-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11095-019-2754-9

Key words

Navigation