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Nanomedicine Scale-up Technologies: Feasibilities and Challenges

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  • Theme: Translational Application of Nano Delivery Systems: Emerging Cancer Therapy
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Abstract

Nanomedicine refers to biomedical and pharmaceutical applications of nanosized cargos of drugs/vaccine/DNA therapeutics including nanoparticles, nanoclusters, and nanospheres. Such particles have unique characteristics related to their size, surface, drug loading, and targeting potential. They are widely used to combat disease by controlled delivery of bioactive(s) or for diagnosis of life-threatening problems in their very early stage. The bioactive agent can be combined with a diagnostic agent in a nanodevice for theragnostic applications. However, the formulation scientist faces numerous challenges related to their development, scale-up feasibilities, regulatory aspects, and commercialization. This article reviews recent progress in the method of development of nanoparticles with a focus on polymeric and lipid nanoparticles, their scale-up techniques, and challenges in their commercialization.

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Abbreviations

NME:

Nanoporous membrane extrusion

SCF:

Supercritical fluid

REFERENCES

  1. Hughes GA. Nanostructure-mediated drug delivery. Nanomedicine. 2005;1:22–30.

    Article  CAS  PubMed  Google Scholar 

  2. Ladj R, Bitar A, Eissa MM, Fessi H, Mugnier Y, Le Dantec R, et al. Polymer encapsulation of inorganic nanoparticles for biomedical applications. Int J Pharm. 2013;458(1):230–41.

    Article  CAS  PubMed  Google Scholar 

  3. Tang L, Cheng J. Nonporous silica nanoparticles for nanomedicine application. Nano Today. 2013;8:290–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Khan MS, Vishakante GD, Siddaramaiah H. Gold nanoparticles: a paradigm shift in biomedical applications. Adv Colloid Interface Sci. 2013;199–200:44–58.

    Article  PubMed  Google Scholar 

  5. Brannon-Peppas L, Blanchette JO. Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev. 2004;56:1649–59.

    Article  CAS  PubMed  Google Scholar 

  6. Langer R. Drug delivery and targeting. Nature. 1998;392:5–10.

    CAS  PubMed  Google Scholar 

  7. Junghanns JAH, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomedicine. 2008;3:295–310.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Petros RA, DeSimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov. 2010;9:615–27.

    Article  CAS  PubMed  Google Scholar 

  9. Merisko-Liversidge E, Liversidge GG, Cooper ER. Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci. 2003;18:113–20.

    Article  CAS  PubMed  Google Scholar 

  10. Bruno RP, McIlwrick R. Microfluidizer processor technology for high performance particle size reduction, mixing and dispersion. Eur J Pharm Biopharm. 1999;56:29–36.

    Google Scholar 

  11. Tunick MH, Van Hecken DL, Cooke PH, et al. Transmission electron microscopy of mozzarella cheeses made from microfluidized milk. J Agric Food Chem. 2002;50:99–103.

    Article  CAS  PubMed  Google Scholar 

  12. Mijajlovic M, Wright D, Zivkovic V, Bi JX, Biggs MJ. Microfluidic hydrodynamic focusing based synthesis of POPC liposomes for model biological systems. Colloids Surf B: Biointerfaces. 2013;104:276–81.

    Article  CAS  PubMed  Google Scholar 

  13. Hung LH, Lee AP. Microfluidic devices for the synthesis of nanoparticles and biomaterials. J of Med Biol Eng. 2007;27:1–6.

    Google Scholar 

  14. Park J, Saffari A, Kumar S, Gunther A, Kumacheva E, Clarke DR, et al. Microfluidic synthesis of polymer and inorganic particulate materials. Ann Rev Mat Res. 2010;40:415–43.

    Article  CAS  Google Scholar 

  15. Napoli M, Atzberger P, Pennathur S. Experimental study of the separation behavior of nanoparticles in micro- and nanochannels. Microfluid Nanofluid. 2011;10:69–80.

    Article  CAS  Google Scholar 

  16. Xing T, Sunarso J, Yang W, Yin Y, Glushenkov AM, Li LH, et al. Ball milling: a green mechanochemical approach for synthesis of nitrogen doped carbon nanoparticles. Nanoscale. 2013;5:7970–6.

    Article  CAS  PubMed  Google Scholar 

  17. Aydin E, Planell JA, Hasirci V. Hydroxyapatite nanorod-reinforced biodegradable poly(Llactic acid) composites for bone plate applications. J Mater Sci Mater Med. 2011;22:2413–27.

    Article  CAS  PubMed  Google Scholar 

  18. Guo P, Hsu TM, Zhao Y, Martin CR, Zare RN. Preparing amorphous hydrophobic drug nanoparticles by nanoporous membrane extrusion. Nanomedicine (Lond). 2013;8:333–41.

    Article  CAS  Google Scholar 

  19. Khinast J, Baumgartner R, Roblegg E. Nano-extrusion: a one-step process for manufacturing of solid nanoparticle formulations directly from the liquid phase. AAPS PharmSciTech. 2013;14:601–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Elizondo E, Veciana J, Ventosa N. Nanostructuring molecular materials as particles and vesicles for drug delivery, using compressed and supercritical fluids. Nanomedicine (Lond). 2012;7:1391–408.

    Article  CAS  Google Scholar 

  21. Sheth P, Sandhu H, Singhal D, Malick W, Shah N, Kislalioglu MS. Nanoparticles in the pharmaceutical industry and the use of supercritical fluid technologies for nanoparticle production. Curr Drug Deliv. 2012;9:269–84.

    Article  CAS  PubMed  Google Scholar 

  22. Byrappa K, Ohara S, Adschiri T. Nanoparticles synthesis using supercritical fluid technology—towards biomedical applications. Adv Drug Deliv Rev. 2008;60:299–327.

    Article  CAS  PubMed  Google Scholar 

  23. Sun YP, Meziani MJ, Pathak P, Qu L. Polymeric nanoparticles from rapid expansion of supercritical fluid solution. Chemistry. 2005;11:1366–73.

    Article  CAS  PubMed  Google Scholar 

  24. Mendoza-Muñoz N, Quintanar-Guerrero D, Allémann E. The impact of the salting out technique on the preparation of colloidal particulate systems for pharmaceutical applications. Recent Pat Drug Deliv Formul. 2012;3:236–49.

    Article  Google Scholar 

  25. Galindo-Rodríguez SA, Puel F, Briançon S, Allémann E, Doelker E, Fessi H. Comparative scale-up of three methods for producing ibuprofen-loaded nanoparticles. Eur J Pharm Sci. 2005;25(4):357–67.

    Article  PubMed  Google Scholar 

  26. Fàbregas A, Miñarro M, García-Montoya E, Pérez-Lozano P, Carrillo C, Sarrate R, et al. Impact of physical parameters on particle size and reaction yield when using the ionic gelation method to obtain cationic polymeric chitosan-tripolyphosphate nanoparticles. Int J Pharm. 2013;446:199–204.

    Article  PubMed  Google Scholar 

  27. Fuchs S, Winter G, Coester C. Ultrasonic resonator technology as a new quality control method evaluating gelatin nanoparticles. J Microencapsul. 2010;27:242–52.

    Article  CAS  PubMed  Google Scholar 

  28. Corrias F, Lai F. New methods for lipid nanoparticles preparation. Recent Pat Drug Deliv Formul. 2011;5:201–13.

    Article  CAS  PubMed  Google Scholar 

  29. Rai S, Paliwal R, Gupta PN, Khatri K, Goyal AK, Vaidya B, et al. Solid lipid nanoparticles (SLNs) as a rising tool in drug delivery science: one step up in nanotechnology. Curr Nanosci. 2008;4:30–44.

    Article  CAS  Google Scholar 

  30. Lamprecht A, Ubrich N, Hombreiro Pérez M, Lehr C, Hoffman M, Maincent P. Biodegradable mono dispersed nanoparticles prepared by pressure homogenization emulsification. Int J Pharm. 1999;184:97–105.

    Article  CAS  PubMed  Google Scholar 

  31. Hou D, Xie C, Huang K, Zhu C. The production and characteristics of solid lipid nanoparticles (SLNs). Biomaterials. 2003;24:1781–5.

    Article  CAS  PubMed  Google Scholar 

  32. Gasco MR. Method for producing solid lipid microspheres having a narrow size distribution. United States patent, US 188837. 1993. 5.

  33. Xie S, Wang S, Zhao B, Han C, Wang M, Zhou W. Effect of PLGA as a polymeric emulsifier on preparation of hydrophilic protein-loaded solid lipid nanoparticles. Colloids Surf B: Biointerfaces. 2008;67:199–204.

    Article  CAS  PubMed  Google Scholar 

  34. Trotta M, Debernardi F, Caputo O. Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique. Int J Pharm. 2003;257:153–60.

    Article  CAS  PubMed  Google Scholar 

  35. Charcosset C, El-Harati A, Fessi H. Preparation of solid lipid nanoparticles using a membrane contactor. J Control Release. 2005;108:112–20.

    Article  CAS  PubMed  Google Scholar 

  36. Bose S, Michniak-Kohn B. Preparation and characterization of lipid based nanosystems for topical delivery of quercetin. Eur J Pharm Sci. 2012;48:442–52.

    Article  PubMed  Google Scholar 

  37. Lamprecht A, Ubrich N, Hombreiro Pérez M, Lehr C, Hoffman M, Maincent P. Influences of process parameters on nanoparticle preparation performed by a double emulsion pressure homogenization technique. Int J Pharm. 2000;196:177–82.

    Article  CAS  PubMed  Google Scholar 

  38. Ghosh P, Han G, De M, Kim CK, Rotello VM. Gold nanoparticles in delivery applications. Adv Drug Deliv Rev. 2008;60:1307–15.

    Article  CAS  PubMed  Google Scholar 

  39. Hu H, Nie L, Feng S, Suo J. Preparation, characterization and in vitro release study of gallic acid loaded silica nanoparticles for controlled release. Pharmazie. 2013;68:401–5.

    CAS  PubMed  Google Scholar 

  40. Bianco A, Kostarelos K, Prato M. Applications of carbon nanotubes in drug delivery. Curr Opin Chem Biol. 2005;9:674–9.

    Article  CAS  PubMed  Google Scholar 

  41. Burnett K, Tyshenko MG. A comparison of human capital levels and the future prospect of the nanotechnology industry in early sector investors and recent emerging markets. Intl J of Nanotech. 2010;7:187–208.

    Article  Google Scholar 

  42. Vladisavljevic GT, Khalid N, Neves MA, Kuroiwa T, Nakajima M, Uemura K, et al. Industrial lab-on-a-chip: design, applications and scale-up for drug discovery and delivery. Adv Drug Deliv Rev. 2013;65(11–12):1626–63.

    Article  CAS  PubMed  Google Scholar 

  43. Hock SC, Ying YM, Wah CL. A review of the current scientific and regulatory status of nanomedicines and the challenges ahead. PDA J Pharm Sci Technol. 2011;65:177–95.

    CAS  PubMed  Google Scholar 

  44. Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases. 2007;2(4):MR17–MR7.

    Article  PubMed  Google Scholar 

  45. Colombo A, Briançon S, Lieto J, Fessi H. Project, design, and use of a pilot plant for nanocapsule production. Drug Dev Ind Pharm. 2001;27(10):1063–72.

    Article  CAS  PubMed  Google Scholar 

  46. Wagner V, Dullaart A, Bock A-K, Zweck A. The emerging nanomedicine landscape. Nat Biotechnol. 2006;24(10):1211–8.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

The authors are thankful to National Corn Growers Association (NCGA) for their research grant support to SP and post-doctoral fellowship to RP.

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Authors and Affiliations

  1. Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, 1010 West Avenue B, MSC 131, Kingsville, Texas, 78363, USA

    Rishi Paliwal & Srinath Palakurthi

  2. Harrison School of Pharmacy, Auburn, Alabama, USA

    R. Jayachandra Babu

Authors
  1. Rishi Paliwal
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  2. R. Jayachandra Babu
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  3. Srinath Palakurthi
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Correspondence to Srinath Palakurthi.

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Guest Editors: Mahavir B. Chougule and Chalet Tan

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Paliwal, R., Babu, R.J. & Palakurthi, S. Nanomedicine Scale-up Technologies: Feasibilities and Challenges. AAPS PharmSciTech 15, 1527–1534 (2014). https://doi.org/10.1208/s12249-014-0177-9

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