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The fabrication and characterization of a PLGA nanoparticle–Pheroid® combined drug delivery system

Abstract

The combination of polymeric nanoparticles (NPs) as a core and lipid vesicles as a shell has emerged to be a robust and promising drug delivery strategy. This study explores the development of a novel combined delivery system where poly d,l, lactic-co-glycolic acid (PLGA) NPs are entrapped within Pheroid® drug delivery system. The solid NPs were combined with the Pheroid® vesicles using two different methods: pre-mix and post-mix. The surface properties of the PLGA NPs were altered through the inclusion (pos-NPs) and exclusion (neg-NPs) of chitosan (CT) and polyethylene glycol (PEG), to evaluate their interaction with the Pheroid® Vesicles. The average particle size of the novel NP–Pheroid® combined system ranged from approximately 1990–2450 nm while the zeta potential (ZP) ranged from −18 to −30 mV, measured using dynamic light scattering (DLS) and electrophoretic velocity techniques, respectively. The NP/Pheroid® mixing ratio experiment indicated that a maximum of 2.5% (w/v) NPs can be optimally added to the Pheroid® vesicles without compromising the structure and the stability of the NP–Pheroid® combined system. Visual analysis of this system was done through transmission electron microscopy (TEM), cryogenic (cryo) TEM and confocal laser scanning microscopy (CLSM) techniques to obtain adequate information of this novel combined drug delivery system which includes the localization of the PLGA NPs with the Pheroid® vesicles.

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References

  1. Zhang L, Chan JM, Gu FX, Rhee J-W, Wang AZ, Radovic-Moreno AF, Alexis F, Langer R, Farokhzad OC (2008) Self-assembled lipid—polymer hybrid nanoparticles: a robust drug delivery platform. ACS Nano 2:1696–1702

    Article  Google Scholar 

  2. Raemdonck K, Braeckmans K, Demeester J, De Smedt SC (2013) Merging the best of both worlds: hybrid lipid-enveloped matrix nanocomposites in drug delivery. Chem Soc Rev 43:444–472

    Article  Google Scholar 

  3. Hadinoto K, Sundaresan A, Cheow WS (2013) Lipid–polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review. Eur J Pharm Biopharm 85:427–443

    Article  Google Scholar 

  4. Saroj S, Baby DA, Sabitha M (2012) Current trends in lipid based delivery systems and its applications in drug delivery. Asian J Pharm Clin Res 5:4–9

    Google Scholar 

  5. Uys CE (2006) Preparation and characterization of Pheroids. Department of Pharmacy, North-west University, Potchefstroom

    Google Scholar 

  6. Grobler, AF. Pharmaceutical applications of Pheroid™ technology, Pharmacy, North-West University, Potchefstroom, 2008

  7. Slabbert C, du Plessis LH, Kotzé AF (2011) Evaluation of the physical properties and stability of two lipid drug delivery systems containing mefloquine. Int J Pharm 409:209–215

    Article  Google Scholar 

  8. Nieuwoudt L-M (2009) The impact of Pheroid™ technology on the bioavailability and efficacy of anti-tuberculosis drugs in an animal model/L. North-West University, Nieuwoudt

    Google Scholar 

  9. Pandey R, Zahoor A, Sharma S, Khuller GK (2003) Nanoparticle encapsulated antitubercular drugs as a potential oral drug delivery system against murine tuberculosis. Tuberculosis 83:373–378

    Article  Google Scholar 

  10. Semete B, Kalombo L, Katata L, Chelule P, Booysen LIJ, Lemmer Y, Naidoo S, Ramalapa B, Hayeshi R, Swai H (2012) Potential of improving the treatment of tuberculosis through nanomedicine. Mol Cryst Liq Cryst 556:317–330

    Article  Google Scholar 

  11. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70:1–20

    Article  Google Scholar 

  12. Hans M, Lowman A (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6:319–327

    Article  Google Scholar 

  13. Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4:145–160

    Article  Google Scholar 

  14. Mufamadi MS, Pillay V, Choonara YE, Du Toit LC, Modi G, Naidoo D, Ndesendo VM. A review on composite liposomal technologies for specialized drug delivery. J Drug Deliv 2011;2011

  15. Park S-H, Oh S-G, Mun J-Y, Han S-S (2006) Loading of gold nanoparticles inside the DPPC bilayers of liposome and their effects on membrane fluidities. Colloids Surf B 48:112–118

    Article  Google Scholar 

  16. Sau TK, Urban AS, Dondapati SK, Fedoruk M, Horton MR, Rogach AL, Stefani FD, Rädler JO, Feldmann J (2009) Controlling loading and optical properties of gold nanoparticles on liposome membranes. Colloids Surf A 342:92–96

    Article  Google Scholar 

  17. Grobler L, Grobler A, Haynes R, Masimirembwa C, Thelingwani R, Steenkamp P, Steyn HS (2014) The effect of the Pheroid delivery system on the in vitro metabolism and in vivo pharmacokinetics of artemisone. Expert Opin Drug Metab Toxicol 10:313–325

    Article  Google Scholar 

  18. Mandal B, Bhattacharjee H, Mittal N, Sah H, Balabathula P, Thoma LA, Wood GC (2013) Core–shell-type lipid–polymer hybrid nanoparticles as a drug delivery platform. Nanomed Nanotechnol Biol Med 9:474–491

    Article  Google Scholar 

  19. Ruozi B, Belletti D, Tombesi A, Tosi G, Bondioli L, Forni F, Vandelli MA (2011) AFM, ESEM, TEM, and CLSM in liposomal characterization: a comparative study. Int J Nanomed 6:557–563

    Article  Google Scholar 

  20. Bershteyn A, Chaparro J, Yau R, Kim M, Reinherz E, Ferreira-Moita L, Irvine DJ (2008) Polymer-supported lipid shells, onions, and flowers. Soft Matter 4:1787–1791

    Article  Google Scholar 

  21. Sollohub K, Cal K (2009) Spray drying technique: II. Current applications in pharmaceutical technology. J Pharm Sci 9999:1–11

    Google Scholar 

  22. Bernkop-Schnürch A, Dünnhaupt S (2012) Chitosan-based drug delivery systems. Eur J Pharm Biopharm 81:463–469

    Article  Google Scholar 

  23. Maldiney T, Richard C, Seguin J, Wattier N, Bessodes M, Scherman D (2011) Effect of core diameter, surface coating, and PEG chain length on the biodistribution of persistent luminescence nanoparticles in mice. ACS Nano 5:854–862

    Article  Google Scholar 

  24. Chen M-C, Mi F-L, Liao Z-X, Hsiao C-W, Sonaje K, Chung M-F, Hsu L-W, Sung H-W (2013) Recent advances in chitosan-based nanoparticles for oral delivery of macromolecules. Adv Drug Deliv Rev 65:865–879

    Article  Google Scholar 

  25. Truong NP, Whittaker MR, Mak CW, Davis TP (2015) The importance of nanoparticle shape in cancer drug delivery. Expert Opin Drug Deliv 12:129–142

    Article  Google Scholar 

  26. Klang V, Valenta C (2011) Lecithin-based nanoemulsions. J Drug Deliv Sci Technol 21:55–76

    Article  Google Scholar 

  27. Thevenot J, Troutier A-L, David L, Delair T, Ladavière C (2007) Steric stabilization of lipid/polymer particle assemblies by poly(ethylene glycol)-lipids. Biomacromolecules 8:3651–3660

    Article  Google Scholar 

  28. Mornet S, Lambert O, Duguet E, Brisson A (2004) The formation of supported lipid bilayers on silica nanoparticles revealed by cryoelectron microscopy. Nano Lett 5:281–285

    Article  Google Scholar 

  29. Kuntsche J, Horst JC, Bunjes H (2011) Cryogenic transmission electron microscopy (cryo-TEM) for studying the morphology of colloidal drug delivery systems. Int J Pharm 417:120–137

    Article  Google Scholar 

  30. Belkoura L, Stubenrauch C, Strey R (2004) Freeze fracture direct imaging: a new freeze fracture method for specimen preparation in cryo-transmission electron microscopy. Langmuir 20:4391–4399

    Article  Google Scholar 

  31. Friedrich H, Frederik PM, de With G, Sommerdijk NA (2010) Imaging of self-assembled structures: interpretation of TEM and Cryo-TEM images. Angew Chem Int Ed 49:7850–7858

    Article  Google Scholar 

  32. Bouchet-Marquis C, Hoenger A (2011) Cryo-electron tomography on vitrified sections: a critical analysis of benefits and limitations for structural cell biology. Micron 42:152–162

    Article  Google Scholar 

  33. Leica EM Sample Preparation Contrasting. In: GmbH LM, editors. LEICA, Vienna, 2013

  34. StainFile, Osmium Tetroxide 2015

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Acknowledgements

The authors would like to thank the National Research Foundation (NRF) and the Department of Science and Technology (DST) for financial support. The authors also thank Dr Matthew Glyn for his technical assistance with the CLSM.

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Correspondence to Madichaba P. Chelopo.

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Chelopo, M.P., Kalombo, L., Wesley-Smith, J. et al. The fabrication and characterization of a PLGA nanoparticle–Pheroid® combined drug delivery system. J Mater Sci 52, 3133–3145 (2017). https://doi.org/10.1007/s10853-016-0602-4

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  • DOI: https://doi.org/10.1007/s10853-016-0602-4

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