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Pharmaceutical Research

, 36:60 | Cite as

Biomimetic Hydroxyapatite a Potential Universal Nanocarrier for Cellular Internalization & Drug Delivery

  • Ashu Srivastav
  • Balasaheb Chandanshive
  • Prajakta Dandekar
  • Deepa KhushalaniEmail author
  • Ratnesh JainEmail author
Research Paper
  • 79 Downloads

Abstract

Purpose

Functional biomaterials can be used as drug loading devices, components for tissue engineering or as biological probes. As such, the design, synthesis and evaluation of a variety of local-drug delivery structures has been undertaken over the past few decades with the ultimate aim of providing materials that can encapsulate a diverse array of drugs (in terms of their sizes, chemical compositions and chemical natures (i.e. hydrophilic/hydrophobic).

Methods

Presented here is the evaluation of specifically hollow 1D structures consisting of nanotubes (NTs) of HAp and their efficacy for cellular internalization using two distinguished anti-cancer model drugs: Paclitaxel (hydrophobic) and Doxorubicin hydrochloride (hydrophilic).

Results

Importantly, it has been observed through this work that HAp NTs consistently showed not only higher drug loading capacity as compared to HAp nanospheres (NSs) but also had better efficacy with respect to cell internalization/encapsulation. The highly porous structure, with large surface area of nanotube morphology, gave the advantage of targeted delivery due to its high drug loading and retention capacity. This was done using the very simple techniques of physical adsorption to load the drug/dye molecules and therefore this can be universally applied to a diverse array of molecules.

Conclusions

Our synthesized nanocarrier can be widely employed in biomedical applications due to its bio-compatible, bio-active and biodegradable properties and as such can be considered to be a universal carrier.

Graphical Abstract

Schematic representation for a comparative study of hydroxyapatite (hollow nanotubes vs solid nanospheres) with variety of drug/ dye molecules

Key Words

confocal microscopy cytotoxicity drug delivery morphology 

Notes

Acknowledgments and Disclosures

The authors are thankful to Department of Science Technology (DST) Nanomission (SR/NM/NS1145/2012) and Prof. Deepa Khushalani is grateful to DAE for plan funds that supported this work. Dr. Prajakta Dandekar is thankful to Ramanujan Fellowship, DST, Government of India (SR/S2/RJN-139/2011) and Dr. Ratnesh Jain is thankful to Ramalingaswami Fellowship, Department of Biotechnology (DBT) Government of India (BT/RLF/Re-entry/51/2011) for the fellowship and research grant.. The authors acknowledge electron microscopy facility of TIFR and Mr. N. Kulkarni for help with XRD. We would also like to thank Mr. Akhil Krishnan for his assistance in HPLC handling. There are no conflicts to declare.

Supplementary material

11095_2019_2594_MOESM1_ESM.docx (871 kb)
ESM 1 (DOCX 870 kb)

References

  1. 1.
    Petros RA, DeSimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov. 2010;9(8):615–27.CrossRefGoogle Scholar
  2. 2.
    Malam Y, Loizidou M, Seifalian AM. Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends Pharmacol Sci. 2009;30(11):592–9.CrossRefGoogle Scholar
  3. 3.
    Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev. 2003;3:329–47.CrossRefGoogle Scholar
  4. 4.
    Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303(5665):1818–22.CrossRefGoogle Scholar
  5. 5.
    Hans ML, Lowman AM. Biodegradable nanoparticles for drug delivery and targeting. Curr Opinion Solid State Mater Sci. 2002;6(4):319–27.CrossRefGoogle Scholar
  6. 6.
    Lavan DA, McGuire T, Langer R. Small-scale systems for in vivo drug delivery. Nat Biotechnol. 2003;21(10):1184–91.CrossRefGoogle Scholar
  7. 7.
    Pattni BS, Chupin VV, Torchilin VP. New developments in liposomal drug delivery. Chem Rev. 2015;115(19):10938–66.CrossRefGoogle Scholar
  8. 8.
    Horcajada P, Chalati T, Serre C, Gillet B, Sebrie C, Baati T, et al. Porous metal–organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. Nat Mater. 2010;9(2):172–8.CrossRefGoogle Scholar
  9. 9.
    Li K, Xiao G, Richardson JJ, Tardy BL, Ejima H, Huang W, et al. Targeted therapy against metastatic melanoma based on self-assembled metal-phenolic Nanocomplexes comprised of green tea Catechin. Adv Sci. 2019:1801688.Google Scholar
  10. 10.
    Li K, Dai Y, Chen W, Yu K, Xiao G, Richardson JJ, et al. Self-assembled metal-phenolic nanoparticles for enhanced synergistic combination therapy against colon cancer. Adv Biosyst. 2019;3(2):1800241.CrossRefGoogle Scholar
  11. 11.
    Percec V, Wilson DA, Leowanawat P, Wilson CJ, Hughes AD, Kaucher MS, et al. Self-assembly of Janus dendrimers into uniform dendrimersomes and other complex architectures. Science. 2010;328(5981):1009–14.CrossRefGoogle Scholar
  12. 12.
    Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release. 2001;70(1–2):1–20.CrossRefGoogle Scholar
  13. 13.
    Norman J, Madurawe RD, Moore CM, Khan MA, Khairuzzaman A. A new chapter in pharmaceutical manufacturing: 3D-printed drug products. Adv Drug Deliv Rev. 2017;108:39–50.CrossRefGoogle Scholar
  14. 14.
    Kakkar A, Traverso G, Farokhzad OC, Weissleder R, Langer R. Evolution of macromolecular complexity in drug delivery systems. Nat Rev Chem. 2017;8:0063.CrossRefGoogle Scholar
  15. 15.
    Dobrovolskaia MA. Understanding nanoparticle immunotoxicity to develop safe medical devices. In: The immune response to implanted materials and devices. Cham: Springer; 2017. p. 63–80.CrossRefGoogle Scholar
  16. 16.
    Rafiei P, Haddadi A. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile. Int J Nanomedicine. 2017;12:935–47.CrossRefGoogle Scholar
  17. 17.
    Ruhe QP, Hedberg EL, Padron NT, Spauwen PH, Jansen JA, Mikos AG. rhBMP-2 release from injectable poly (DL-lactic-co-glycolic acid)/calcium-phosphate cement composites. JBJS. 2003;85:75–81.CrossRefGoogle Scholar
  18. 18.
    Dhar S, Gu FX, Langer R, Farokhzad OC, Lippard SJ. Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt (IV) prodrug-PLGA–PEG nanoparticles. Proc Natl Acad Sci. 2008;105(45):17356–61.Google Scholar
  19. 19.
    Zong X, Li S, Chen E, Garlick B, Kim KS, Fang D, et al. Prevention of postsurgery-induced abdominal adhesions by electrospun bioabsorbable nanofibrous poly (lactide-co-glycolide)-based membranes. Ann Surg. 2004;240(5):910.CrossRefGoogle Scholar
  20. 20.
    Vallet-Regi M, Ramila A, Del Real RP, Pérez-Pariente J. A new property of MCM-41: drug delivery system. Chem Mater. 2001;13(2):308–11.CrossRefGoogle Scholar
  21. 21.
    Hunter AC, Moghimi SM. Smart polymers in drug delivery: a biological perspective. Polym Chem. 2017;1:41–51.CrossRefGoogle Scholar
  22. 22.
    Liong M, Lu J, Kovochich M, Xia T, Ruehm SG, Nel AE, et al. Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. ACS Nano. 2008;2(5):889–96.CrossRefGoogle Scholar
  23. 23.
    Anselmo AC, Mitragotri S. A review of clinical translation of inorganic nanoparticles. AAPS J. 2015;5:1041–54.CrossRefGoogle Scholar
  24. 24.
    Ma MY, Zhu YJ, Li L, Cao SW. Nanostructured porous hollow ellipsoidal capsules of hydroxyapatite and calcium silicate: preparation and application in drug delivery. J Mater Chem. 2008;18(23):2722–7.CrossRefGoogle Scholar
  25. 25.
    Sahoo SK, Labhasetwar V. Nanotech approaches to drug delivery and imaging. Drug Discov Today. 2003;24:1112–20.CrossRefGoogle Scholar
  26. 26.
    Arruebo M, Fernández-Pacheco R, Ibarra MR, Santamaría J. Magnetic nanoparticles for drug delivery. Nano Today. 2007;2(3):22–32.CrossRefGoogle Scholar
  27. 27.
    Liechty WB, Kryscio DR, Slaughter BV, Peppas NA. Polymers for drug delivery systems. Annu Rev Chem Biomol Eng. 2010;1:149–73.CrossRefGoogle Scholar
  28. 28.
    Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nanoparticles as drug delivery systems. Pharmacol Rep. 2012;64(5):1020–37.CrossRefGoogle Scholar
  29. 29.
    Svenson S, Tomalia DA. Dendrimers in biomedical applications—reflections on the field. Adv Drug Deliv Rev. 2012;64:102–15.CrossRefGoogle Scholar
  30. 30.
    Elsabahy M, Wooley KL. Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev. 2012;41(7):2545–61.CrossRefGoogle Scholar
  31. 31.
    Park JH, Gu L, Von Maltzahn G, Ruoslahti E, Bhatia SN, Sailor MJ. Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nat Mater. 2009;4:331.CrossRefGoogle Scholar
  32. 32.
    Sun X, Liu Z, Welsher K, Robinson JT, Goodwin A, Zaric S, et al. Nano-graphene oxide for cellular imaging and drug delivery. Nano Res. 2008;1(3):203–12.CrossRefGoogle Scholar
  33. 33.
    Dasgupta S, Auth T, Gompper G. Shape and orientation matter for the cellular uptake of nonspherical particles. Nano Lett. 2014;14(2):687–93.CrossRefGoogle Scholar
  34. 34.
    Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012;63:185–98.CrossRefGoogle Scholar
  35. 35.
    Truong NP, Whittaker MR, Mak CW, Davis TP. The importance of nanoparticle shape in cancer drug delivery. Expert Opin Drug Deliv. 2015;12(1):129–42.CrossRefGoogle Scholar
  36. 36.
    Chen J, Clay NE, Park NH, Kong H. Non-spherical particles for targeted drug delivery. Chem Eng Sci. 2015;125:20–4.CrossRefGoogle Scholar
  37. 37.
    Chandanshive B, Dyondi D, Ajgaonkar VR, Banerjee R, Khushalani D. Biocompatible calcium phosphate based tubes. J Mater Chem. 2010;20(33):6923–8.CrossRefGoogle Scholar
  38. 38.
    Chandanshive B, Rai P, Rossi AL, Ersen O, Khushalani D. Synthesis of hydroxyapatite nanotbes for biomedical applications. Mater Sci Eng C. 2013;33:2981–6.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemical EngineeringInstitute of Chemical TechnologyMumbaiIndia
  2. 2.Department of Chemical SciencesTata Institute of Fundamental ResearchMumbaiIndia
  3. 3.Department of Pharmaceutical Science & TechnologyInstitute of Chemical TechnologyMumbaiIndia

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