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Nanocrystals for Improving the Biopharmaceutical Performance of Hydrophobic Drugs

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The ADME Encyclopedia

Synonyms

Nanocrystals; Nanoparticles; Nanostructures; Nanosystems

Definition

Nanocrystals are formed by 100% of pure drug (carrier-free particles) and often stabilized with a polymer or surfactant to avoid or minimize the agglomeration or aggregation phenomena [1, 2].

Introduction

The term nanometer indicates a scale order of 10−9 m in spatial dimension, which is above the typical dimensions of the atomic diameter by only one order of magnitude (10−10m). Therefore, for a material to be considered as nanomaterials, at least one of their dimensions must range between 1 and 1000 nm. The latest advances focused on the manipulation and control of materials in the nanoscale range have opened up new horizons in several fields of science, including medicine. To understand the possibilities offered by this novel technology, it is crucial to realize that nanostructures present sizes similar to large biological macromolecules such as enzymes and receptors, being much smaller than human cells...

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References

  1. Junyaprasert VB, Morakul B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J Pharm Sci. 2015;10:13–23. https://doi.org/10.1016/j.ajps.2014.08.005.

    Article  Google Scholar 

  2. Mohammad IS, Hu H, Yin L, He W. Drug nanocrystals: fabrication methods and promising therapeutic applications. Int J Pharm. 2019;562:187–202. https://doi.org/10.1016/j.ijpharm.2019.02.045.

    Article  CAS  PubMed  Google Scholar 

  3. Gao L, Liu G, Ma J, Wang X, Zhou L, Li X, Wang F. Application of drug nanocrystal technologies on oral drug delivery of poorly soluble drugs. Pharm Res. 2012;30:307–24. https://doi.org/10.1007/s11095-012-0889-z.

    Article  CAS  PubMed  Google Scholar 

  4. Chen ML, Jhon M, Lee SL, Tyner KM. Development consideration for nanocrystal drug product. AAPS J. 2017;19:642–51. https://doi.org/10.1208/s12248-017-0064-x.

    Article  CAS  PubMed  Google Scholar 

  5. Abuzar SM, Hyun SM, Kim JH, Park HJ, Kim MS, Park JS, Hwang SJ. Enhancing the solubility and bioavailability of poorly water-soluble drugs using supercritical antisolvent (SAS) process. Int J Pharm. 2018;538:1–13. https://doi.org/10.1016/j.ijpharm.2017.12.041.

    Article  CAS  PubMed  Google Scholar 

  6. Al-Hamidi H, Edwards AA, Mohammad MA, Nokhodchi A. To enhance dissolution rate of poorly water-soluble drugs: glucosamine hydrochloride as a potential carrier in solid dispersion formulations. Colloids Surf B Biointerfaces. 2010;76:170–8. https://doi.org/10.1016/j.colsurfb.2009.10.030.

    Article  CAS  PubMed  Google Scholar 

  7. Al-Kassas R, Bansal M, Shaw J. Nanosizing techniques for improving bioavailability of drugs. J Control Release. 2017;260:202–12. https://doi.org/10.1016/j.jconrel.2017.06.003.

    Article  CAS  PubMed  Google Scholar 

  8. Williams RO III, Watts AB, Miller DA, editors. Formulating poorly water soluble drugs. New York: Springer; 2012.

    Google Scholar 

  9. Kim K, Lee I, Centrone A, Hatton TA, Myerson AS. Formation of nanosized organic molecular crystal on engineered surface. J Am Chem Soc. 2009;131:18212–3. https://doi.org/10.1021/ja908055y.

    Article  CAS  PubMed  Google Scholar 

  10. Chan HK, Kwok PCL. Production methods for nanodrug particles using bottom-up approach. Adv Drug Deliv Rev. 2011;63:406–16. https://doi.org/10.1016/j.addr.2011.03.011.

    Article  CAS  PubMed  Google Scholar 

  11. Fontana F, Figueiredo P, Zhang P, Hirvonen JT, Liu D, Santos HA. Production of pure drug nanocrystals and nano co-crystals by confinement methods. Adv Drug Deliv Rev. 2018;131:3–21. https://doi.org/10.1016/j.addr.2018.05.002.

    Article  CAS  PubMed  Google Scholar 

  12. Fu X, Cai J, Zhang X, Li WD, Ge H, Hu Y. Top-down fabrication of shape-controlled, monodisperse nanoparticles for biomedical applications. Adv Drug Deliv Rev. 2018;132:169–87. https://doi.org/10.1016/j.addr.2018.07.006.

    Article  CAS  PubMed  Google Scholar 

  13. Chang TL, Zhan H, Liang D, Liang JF. Nanocrystal technology for drug formulation and delivery. Front Chem Sci Eng. 2015;9:1–14. https://doi.org/10.1007/s11705-015-1509-3.

    Article  CAS  Google Scholar 

  14. Singer A, Barakat Z, Mohapatra S, Mohapatra SS. Nanoscale drug-delivery systems: In vitro and In vivo characterization. In: Mohapatra S, Ranjan S, Dasgupta N, Kumar Mishra R, Thomas S, editors. Nanocarriers for drug delivery: nanoscale drug-delivery systems; 2019. p. 395–419. https://doi.org/10.1016/B978-0-12-814033-8.00013-8.

    Chapter  Google Scholar 

  15. Wu L, Zhang J, Watanabe W. Physical and chemical stability of drug nanoparticles. Adv Drug Deliv Rev. 2011;63:456–69. https://doi.org/10.1016/j.addr.2011.02.001.

    Article  CAS  PubMed  Google Scholar 

  16. Malamatari M, Taylor KGM, Malamataris S, Douroumis D, Kachrimanis K. Pharmaceutical nanocrystals production by wet milling and applications. Drug Discov Today. 2018;23:534–47. https://doi.org/10.1016/j.drudis.2018.01.016.

    Article  CAS  PubMed  Google Scholar 

  17. Date AA, Hanes J, Ensign LM. Nanoparticles for oral delivery: design, evaluation and state-of-the-art. J Control Release. 2016;240:504–26. https://doi.org/10.1016/j.jconrel.2016.06.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sant A, Tao SL, Fisher OZ, Xu Q, Peppas NA, Khademhosseini A. Microfabrication technologies for oral drug delivery. Adv Drug Deliv Rev. 2012;64:496–507. https://doi.org/10.1016/j.addr.2011.11.013.

    Article  CAS  PubMed  Google Scholar 

  19. Leal J, Smyth HDC, Gosh D. Physicochemical properties of mucus and their impact on transmucosal drug delivery. Int J Pharm. 2017;523:555–72. https://doi.org/10.1016/j.ijpharm.2017.09.018.

    Article  CAS  Google Scholar 

  20. Fu Q, Sun J, Zhang D, Li M, Wang Y, Ling G, Liu X, Sun Y, Sui X, Luo C, Sun L, Han X, Lian H, Zhu M, Wang S, He Z. Nimodipine nanocrystals for oral bioavailability improvement (part I): preparation, characterization and pharmacokinetic studies. Colloids Surf B: Biointerfaces. 2013;109:161–6. https://doi.org/10.1016/j.colsurfb.2013.01.066.

    Article  CAS  PubMed  Google Scholar 

  21. Fu Q, Sun J, Ai X, Zhang P, Li M, Wang Y, Liu X, Sun Y, Sui X, Sun L, Han X, Zhu M, Zhang Y, Wang S, He Z. Nimodipine nanocrystals for oral bioavailability improvement: role of mesenteric lymph transport in the oral absorption. Int J Pharm. 2013;448:290–7. https://doi.org/10.1016/j.ijpharm.2013.01.065.

    Article  CAS  PubMed  Google Scholar 

  22. Patel A, Cholkar K, Agrahari V, Mitra AK. Ocular drug delivery systems: an overview. World J Pharmacol. 2013;2:47–64. https://doi.org/10.5497/wjp.v2.i2.47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sharma OP, Patel V, Mehta T. Nanocrystal for ocular drug delivery: hope or hype. Drug Deliv Transl Res. 2016;6:399–413. https://doi.org/10.1007/s13346-016-0292-0.

    Article  CAS  PubMed  Google Scholar 

  24. Donia M, Osman R, Awad GAS, Mortada N. Polypeptide and glycosaminoglycan polysaccharide as stabilizing polymers in nanocrystals for a safe ocular hypotensive effect. Int J Biol Macromol. 2020;162:1690–710. https://doi.org/10.1016/j.ijbiomac.2020.07.306.

    Article  CAS  Google Scholar 

  25. Gulati N, Gupta H. Parenteral drug delivery: a review. Recent Pat Drug Deliv Formul. 2011;5:133–45. https://doi.org/10.2174/187221111795471391.

    Article  CAS  PubMed  Google Scholar 

  26. Müller K, Fedosov DA, Gompper G. Margination of micro- and nano-particles in blood flow and its effect on drug delivery. Sci Rep. 2014;4:4871. https://doi.org/10.1038/srep04871.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Liu Y, Huang L, Liu F. Paclitaxel nanocrystals for overcoming multidrug resistance in cancer. Mol Pharm. 2010;7:863–9. https://doi.org/10.1021/mp100012s.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Renehan AG, Booth C, Potten CS. What is apoptosis, and why is it important? BMJ. 2001;322:1536–8. https://doi.org/10.1136/bmj.322.7301.1536.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Durán N, Guterres SS, Alves OL, editors. Nanotoxicology. materials, methodologies, and assessments. New York: Springer Science+Business Media; 2014. https://doi.org/10.1007/978-1-4614-8993-1.

    Book  Google Scholar 

  30. Smolkova B, Dusinska M, Gabelova A. Nanomedicine and epigenome. Possible health risks. Food Chem Toxicol. 2017;109:780–96. https://doi.org/10.1016/j.fct.2017.07.020.

    Article  CAS  PubMed  Google Scholar 

  31. Hillegass JM, Shukla A, Lathrop SA, MacPherson MB, Fukagawa NK, Mossman BT. Assessing nanotoxicity in cells in vitro. WIREs Nanomed Nanobiotechnol. 2009;2:219–31. https://doi.org/10.1002/wnan.54.

    Article  CAS  Google Scholar 

  32. Lojk J, Repas J, Veranič P, Bregar VB, Pavlin M. Toxicity mechanisms of selected engineered nanoparticles on human neural cells in vitro. Toxicology. 2020;432:152364. https://doi.org/10.1016/j.tox.2020.152364.

    Article  CAS  PubMed  Google Scholar 

  33. Ostermann M, Sauter A, Xue Y, Birkeland E, Schoelermann J, Holst B, Cimpan MR. Label-free impedance flow cytometry for nanotoxicity screening. Sci Rep. 2020;10:142. https://doi.org/10.1038/s41598-019-56705-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Oberdörster G. Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology. J Intern Med. 2010;267:89–105. https://doi.org/10.1111/j.1365-2796.2009.02187.x.

    Article  CAS  PubMed  Google Scholar 

  35. Keck CM, Müller RH. Nanotoxicological classification system (NCS) – a guide for the risk benefit assessment of nanoparticle drug delivery systems. Eur J Pharm Biopharm. 2013;84:445–8. https://doi.org/10.1016/j.ejpb.2013.01.001.

    Article  CAS  PubMed  Google Scholar 

  36. Bruge F, Damiani E, Marcheggiani F, Offerta A, Puglia C, Tiano L. A comparative study on the possible cytotoxic effects of different nanostructured lipid carrier (NLC) compositions in human dermal fibroblasts. Int J Pharm. 2015;495:879–85. https://doi.org/10.1016/j.ijpharm.2015.09.033.

    Article  CAS  PubMed  Google Scholar 

  37. Fangueiro JF, Andreani T, Egea MA, Garcia ML, Souto SB, Silva AM, Souto EB. Design of cationic lipid nanoparticles for ocular delivery: development, characterization and cytotoxicity. Int J Pharm. 2014;461:64–73. https://doi.org/10.1016/j.ijpharm.2013.11.025.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang H, Hu H, Zhang H, Dai W, Wang X, Wang X, Zhan Q. Effects of PEGylated paclitaxel nanocrystals on breast cancer and its lung metastasis. Nanoscale. 2015;7:10790–800. https://doi.org/10.1039/c4nr07450e.

    Article  CAS  PubMed  Google Scholar 

  39. Webster R, Elliott V, Park BK, Walker D, Hankin M, Taupin P. PEG and PEG conjugates toxicity: towards an understanding of the toxicity of PEG and its relevance to PEGylated biologicals. In: Veronese FM, editor. PEGylated protein drugs: basic science and clinical applications. Milestones in drug therapy. Basel: Birkhäuser; 2009.

    Google Scholar 

  40. Ahamed M, Posgai R, Gorey TJ, Nielsen M, Hussain SM, Rowe JJ. Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster. Toxicol Appl Pharmacol. 2010;242:263–9. https://doi.org/10.1016/j.taap.2009.10.016.

    Article  CAS  PubMed  Google Scholar 

  41. Sushma HK, Iqbal A, Pradip KD. In-vitro toxicity induced by quartz nanoparticles: role of ER stress. Toxicology. 2018;404:1–9. https://doi.org/10.1016/j.tox.2018.05.001.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Departamento de Ciencias Básicas y Aplicadas, Universidad Nacional del Chaco Austral, Pcia. Roque Sáenz Peña, CONICET, Chaco, Argentina

    Katia Pamela Seremeta & Nora Beatriz Okulik

  2. Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, IQUIR-CONICET, Rosario, Argentina

    Giselle Rocío Bedogni & Claudio Javier Salomon

Authors
  1. Katia Pamela Seremeta
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  2. Giselle Rocío Bedogni
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  3. Nora Beatriz Okulik
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  4. Claudio Javier Salomon
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Corresponding author

Correspondence to Claudio Javier Salomon .

Section Editor information

  1. Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of la Plata (UNLP) - Argentinean National Council of Scientific and Technical Research (CONICET), La Plata, Buenos Aires, Argentina

    Alan Talevi

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Seremeta, K.P., Bedogni, G.R., Okulik, N.B., Salomon, C.J. (2021). Nanocrystals for Improving the Biopharmaceutical Performance of Hydrophobic Drugs. In: The ADME Encyclopedia. Springer, Cham. https://doi.org/10.1007/978-3-030-51519-5_104-1

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  • DOI: https://doi.org/10.1007/978-3-030-51519-5_104-1

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  • Print ISBN: 978-3-030-51519-5

  • Online ISBN: 978-3-030-51519-5

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