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Hydroxyapatite-coated liposomes for the controlled release of quantum dots and bupivacaine

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Abstract

This work reports the development of hydroxyapatite-coated liposomes to encapsulate drug bupivacaine and quantum dots (CdSe) to be used as a theranostic tool. Systems like this allow monitoring drug distribution in vivo (because of the quantum dots) and they can modulate the rate of drug delivery by increasing drug concentration in situ (due to the hydroxyapatite coating). Liposomes were prepared by the injection technique, and their hydroxyapatite coating was obtained by co-precipitation of calcium and phosphate precursors. The increase in diameter and decrease in zeta potential of the hydroxyapatite-coated liposomes (LHAP) when compared to conventional liposomes evidenced that a core–shell was formed around the vesicles. X-ray diffraction and infrared spectroscopy measurements confirmed the presence of hydroxyapatite in the coating. The liposomes were then functionalized with CdSe to be used as theranostic and detected by photoluminescence. The bupivacaine was incorporated in liposomes/hydroxyapatite and its in vitro release kinetics was modulated, showing slower rates than those measured with the conventional liposomes.

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References

  1. T. Matsumoto, M. Okazaki, M. Inoue, S. Yamaguchi, T. Kusunose, T. Toyonaga, Y. Hamada, J. Takahashi, Hydroxyapatite particles as a controlled release carrier of protein. Biomaterials 25, 3807–3812 (2004). https://doi.org/10.1016/j.biomaterials.2003.10.081

    Article  CAS  Google Scholar 

  2. E.C. Gaetti Jardim, P.L. dos Santos, J.F. Santiago Junior, E.G. Jardim Júnio, A.M. Aranega, I.R. Garcia Júnior, Enxerto ósseo em odontologia bone graft in odontology. Rev. Odontológica Araçatuba. 30, 24–28 (2009)

    Google Scholar 

  3. P. Kamalanathan, S. Ramesh, L.T. Bang, A. Niakan, C.Y. Tan, J. Purbolaksono, H. Chandran, W.D. Teng, Synthesis and sintering of hydroxyapatite derived from eggshells as a calcium precursor. Ceram. Int. 40, 16349–16359 (2014). https://doi.org/10.1016/j.ceramint.2014.07.074

    Article  CAS  Google Scholar 

  4. A. Stoch, W. Jastrzȩbski, A. Brozek, J. Stoch, J. Szaraniec, B. Trybalska, G. Kmita, FTIR absorption-reflection study of biomimetic growth of phosphates on titanium implants. J. Mol. Struct. 555, 375–382 (2000). https://doi.org/10.1016/S0022-2860(00)00623-2

    Article  CAS  Google Scholar 

  5. M. Colilla, M. Manzano, M. Vallet-Ragí, Recent advances in ceramic implants as drug delivery systems for biomedical applications. Int. J. Nanomed. 3, 403–414 (2008). https://doi.org/10.2147/IJN.S3548

    Article  CAS  Google Scholar 

  6. T. Nii, F. Ishii, Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method. Int. J. Pharm. 298, 198–205 (2005). https://doi.org/10.1016/j.ijpharm.2005.04.029

    Article  CAS  Google Scholar 

  7. V. Mišković-Stanković, A. Janković, S. Eraković, K.Y. Rhee, Graphene based biomedical composite coatings produced by electrophoretic deposition on titanium. Eurasian Chem. J. 17, 3–15 (2015)

    Article  Google Scholar 

  8. W.T. Al-Jamal, K. Kostarelos, Liposomes: from a clinically established drug delivery system to a nanoparticle platform for theranostic nanomedicine. Acc. Chem. Res. 44, 1094–1104 (2011). https://doi.org/10.1021/ar200105p

    Article  CAS  Google Scholar 

  9. K.P. Sanosh, M.C. Chu, A. Balakrishnan, T.N. Kim, S.J. Cho, Utilization of biowaste eggshells to synthesize nanocrystalline hydroxyapatite powders. Mater. Lett. 63, 2100–2102 (2009). https://doi.org/10.1016/j.matlet.2009.06.062

    Article  CAS  Google Scholar 

  10. V. Hengst, C. Oussoren, T. Kissel, G. Storm, Bone targeting potential of bisphosphonate-targeted liposomes. Preparation, characterization and hydroxyapatite binding in vitro. Int. J. Pharm. 331, 224–227 (2007). https://doi.org/10.1016/j.ijpharm.2006.11.024

    Article  CAS  Google Scholar 

  11. Y. Cai, T. Gao, S. Fu, P. Sun, Development of zoledronic acid functionalized hydroxyapatite loaded polymeric nanoparticles for the treatment of osteoporosis. Exp. Ther. Med. 16, 704–710 (2018). https://doi.org/10.3892/etm.2018.6263

    Article  CAS  Google Scholar 

  12. Q. Xu, Y. Tanaka, J.T. Czernuszka, Encapsulation and release of a hydrophobic drug from hydroxyapatite coated liposomes. Biomaterials 28, 2687–2694 (2007). https://doi.org/10.1016/j.biomaterials.2007.02.007

    Article  CAS  Google Scholar 

  13. M. Stigter, J. Bezemer, K. De Groot, P. Layrolle, Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy. J. Control Release 99, 127–137 (2004). https://doi.org/10.1016/j.jconrel.2004.06.011

    Article  CAS  Google Scholar 

  14. K. Yamamura, H. Iwata, T. Yotsuyanagi, Synthesis of antibiotic-loaded hydroxyapatite beads and in vitro drug release testing. J. Biomed. Mater. Res. 26, 1053–1064 (1992). https://doi.org/10.1002/jbm.820260807

    Article  CAS  Google Scholar 

  15. M. Danaei, M. Dehghankhold, S. Ataei, F. Hasanzadeh Davarani, R. Javanmard, A. Dokhani, S. Khorasani, M.R. Mozafari, Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 10, 1–17 (2018). https://doi.org/10.3390/pharmaceutics10020057

    Article  CAS  Google Scholar 

  16. G. Pabst, N. Kučerka, M.-P. Nieh, J. Katsaras, Liposomes, Lipid Bilayers and Model Membranes: From Basic Research to Application, 1st edn. (CRC Press, Boca Raton, 2014). https://doi.org/10.1201/b16617

  17. E. de Paula, J.D. Oliveira, F.F. de Lima, L.N. de Morais Ribeiro, Liposome-based delivery of therapeutic agents, in Controlled Drug Delivery Systems, 1st edn., ed. by E.C. Opara (Taylor & Francis, New York, 2020), pp. 299–324. https://doi.org/10.1201/9780429197833-16

  18. L. Sercombe, T. Veerati, F. Moheimani, S.Y. Wu, A.K. Sood, S. Hua, Advances and challenges of liposome assisted drug delivery. Front. Pharmacol. 6, 1–13 (2015). https://doi.org/10.3389/fphar.2015.00286

    Article  CAS  Google Scholar 

  19. K. Sarabandi, S.M. Jafari, M. Mohammadi, Z. Akbarbaglu, A. Pezeshki, M. KhakbazbHeshmati, Production of reconstitutable nanoliposomes loaded with flaxseed protein hydrolysates: stability and characterization. Food Hydrocoll. 96, 442–450 (2019). https://doi.org/10.1016/j.foodhyd.2019.05.047

    Article  CAS  Google Scholar 

  20. C.F. de Freitas, I.R. Calori, A.C.P. da Silva, L.V. de Castro, F. Sato, D. Silva Pellosi, A.L. Tessaro, W. Caetano, N. Hioka, PEG-coated vesicles from Pluronic/lipid mixtures for the carrying of photoactive erythrosine derivatives. Colloids Surf. B 175, 530–544 (2019). https://doi.org/10.1016/j.colsurfb.2018.12.031

    Article  CAS  Google Scholar 

  21. H.T. Schmidt, A.E. Ostafin, Liposome directed growth of calcium phosphate nanoshells. Adv. Mater. 14, 532–535 (2002). https://doi.org/10.1002/1521-4095(20020404)14:7%3c532::AID-ADMA532%3e3.0.CO;2-4

    Article  CAS  Google Scholar 

  22. M.G. Bellino, A.E. Regazzoni, Coating liposomes with yttrium basic carbonate: making hybrid nanocapsules. J. Colloid Interface Sci. 333, 812–815 (2009). https://doi.org/10.1016/j.jcis.2009.02.035

    Article  CAS  Google Scholar 

  23. A. Fihri, C. Len, R.S. Varma, A. Solhy, Hydroxyapatite: a review of syntheses, structure and applications in heterogeneous catalysis. Coord. Chem. Rev. 347, 48–76 (2017). https://doi.org/10.1016/j.ccr.2017.06.009

    Article  CAS  Google Scholar 

  24. Q. Wang, Y. Chao, Multifunctional quantum dots and liposome complexes in drug delivery. J. Biomed. Res. 32, 91–106 (2017). https://doi.org/10.7555/JBR.31.20160146

    Article  Google Scholar 

  25. J. Batalla, H. Cabrera, E. San Martín-Martínez, D. Korte, A. Calderón, E. Marín, Encapsulation efficiency of CdSe/ZnS quantum dots by liposomes determined by thermal lens microscopy. Biomed. Opt. Express 6, 3898 (2015). https://doi.org/10.1364/BOE.6.003898

    Article  CAS  Google Scholar 

  26. N.F. Mohammad, R. Othman, F. Yee-Yeoh, Nanoporous hydroxyapatite preparation method for drug delivery. Rev. Adv. Mater. Sci. 38, 138–147 (2014)

    CAS  Google Scholar 

  27. E. de Paula, S. Schreier, Use of a novel method for determination of partition coefficients to compare the effect of local anesthetics on membrane structure. Biochim. Biophys. Acta. 1240, 25–33 (1995). https://doi.org/10.1016/0005-2736(95)00155-6

    Article  Google Scholar 

  28. L.F. Fraceto, A. Spisni, S. Schreier, E. De Paula, Differential effects of uncharged aminoamide local anesthetics on phospholipid bilayers, as monitored by 1H-NMR measurements. Biophys. Chem. 115, 11–18 (2005). https://doi.org/10.1016/j.bpc.2004.12.003

    Article  CAS  Google Scholar 

  29. H. Gheisari, E. Karamian, M. Abdellahi, A novel hydroxyapatite–Hardystonite nanocomposite ceramic A novel hydroxyapatite–Hardystonite nanocomposite ceramic. Ceram. Int. 41, 5967–5975 (2015). https://doi.org/10.1016/j.ceramint.2015.01.033

    Article  CAS  Google Scholar 

  30. H.T. Schmidt, B.L. Gray, P.A. Wingert, A.E. Ostafin, Assembly of aqueous-cored calcium phosphate nanoparticles for drug delivery. Chem. Mater. 16, 4942–4947 (2004). https://doi.org/10.1021/cm040056i

    Article  CAS  Google Scholar 

  31. M.B. Abramson, W.T. Norton, R. Katzman, Study of ionic structures in phospholipids by infrared spectra. J. Biol. Chem. 240, 2389–2395 (1965)

    Article  CAS  Google Scholar 

  32. D.A. Skoog, S.R. Crouch, F.J. Holler, Instrumental Analysis Principles, 7th edn. (Cengage Learning, Boston, 2006)

    Google Scholar 

  33. K. Tahara, S. Fujimoto, F. Fujii, Y. Tozuka, T. Jin, H. Takeuchi, Quantum dot-loaded liposomes to evaluate the behavior of drug carriers after oral administration. J. Pharm. 2013, 1–6 (2013). https://doi.org/10.1155/2013/848275

    Article  CAS  Google Scholar 

  34. L.W. Zhang, C.J. Wen, S.A. Al-Suwayeh, T.C. Yen, J.Y. Fang, Cisplatin and quantum dots encapsulated in liposomes as multifunctional nanocarriers for theranostic use in brain and skin. J. Nanoparticle Res. (2012). https://doi.org/10.1007/s11051-012-0882-9

    Article  Google Scholar 

  35. S.R. Schaffazick, A.R. Pohlmann, T. Dalla-Costa, S.S. Guterres, Freeze-drying polymeric colloidal suspensions: nanocapsules, nanospheres and nanodispersion. A comparative study. Eur. J. Pharm. Biopharm. 56, 501–505 (2003). https://doi.org/10.1016/S0939-6411(03)00139-5

    Article  CAS  Google Scholar 

  36. S.A. Lourenço, et al., Surface Engineering in Alloyed CdSe/CdSexCdS1–x/CdS Core-Shell Colloidal Quantum Dots for Enhanced Optoelectronic Applications, in Emerging Research in Science and Engineering Based on Advanced Experimental and Computational Strategies. Engineering Materials, ed. by F. La Porta, C. Taft (Springer, Cham, 2020). https://doi.org/10.1007/978-3-030-31403-3_7

  37. H. Jin, B. Baek, D. Kim, F. Wu, J.D. Batteas, J. Cheon, D.H. Son, Effects of direct solvent-quantum dot interaction on the optical properties of colloidal monolayer WS2 quantum dots. Nano Lett. 17, 7471–7477 (2017). https://doi.org/10.1021/acs.nanolett.7b03381

    Article  CAS  Google Scholar 

  38. Q. Xu, J.T. Czernuszka, Controlled release of amoxicillin from hydroxyapatite-coated poly(lactic-co-glycolic acid) microspheres. J. Control Release 127, 146–153 (2008). https://doi.org/10.1016/j.jconrel.2008.01.017

    Article  CAS  Google Scholar 

  39. A.R. de Araújo, L.N.M. de Ribeiro, E. de Paula, Lipid-based carriers for the delivery of local anesthetics. Expert Opin. Drug Deliv. 16, 701–714 (2019). https://doi.org/10.1080/17425247.2019.1629415

    Article  CAS  Google Scholar 

  40. H.P. Thakkar, A.K. Baser, M.P. Parmar, K.H. Patel, R. Ramachandra Murthy, Vincristine-sulphateloaded liposome-templated calcium phosphate nanoshell as potential tumor-targeting delivery system. J. Liposome Res. 22, 139–147 (2012). https://doi.org/10.3109/08982104.2011.633266

    Article  CAS  Google Scholar 

  41. C.D.M. Donegá, P. Liljeroth, D. Vanmaekelbergh, Physicochemical evaluation of the hot-injection method, a synthesis route for monodisperse nanocrystals. Small 1, 1152–1162 (2005). https://doi.org/10.1002/smll.200500239

    Article  CAS  Google Scholar 

  42. S. Hua, S.Y. Wu, The use of lipid-based nanocarriers for targeted pain therapies. Front. Pharmacol. 4, 143–150 (2013). https://doi.org/10.3389/fphar.2013.00143

  43. D. Zucker, D. Marcus, Y. Barenholz, A. Goldblum, Liposome drugs’ loading efficiency: a working model based on loading conditions and drug’s physicochemical properties. J. Control. Release. 139, 73–80 (2009). https://doi.org/10.1016/j.jconrel.2009.05.036

    Article  CAS  Google Scholar 

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Acknowledgments

The authors are thankful to the Spectroscopy laboratory at the State University of Londrina (UEL), and Labmult—Laboratory of Technological Federal University of Paraná, Londrina, PR, for use of their facilities. The capes-ds scholarship program (Grant Number 1795788).

Funding

This study was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes-ds program) (grant number 1795788).

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Correspondence to Luis Fernando Cabeça.

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Lopes, F.F., de Freitas, C.F., de Paula, E. et al. Hydroxyapatite-coated liposomes for the controlled release of quantum dots and bupivacaine. Journal of Materials Research 36, 3021–3030 (2021). https://doi.org/10.1557/s43578-021-00292-5

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