Journal of Materials Science

, Volume 52, Issue 6, pp 3133–3145 | Cite as

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

  • Madichaba P. ChelopoEmail author
  • Lonji Kalombo
  • James Wesley-Smith
  • Anne Grobler
  • Rose Hayeshi
Original Paper


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.


Chitosan Zeta Potential Dynamic Light Scattering Dynamic Light Scattering Combine System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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.


  1. 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 2:1696–1702CrossRefGoogle Scholar
  2. 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 43:444–472CrossRefGoogle Scholar
  3. 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 85:427–443CrossRefGoogle Scholar
  4. 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 5:4–9Google Scholar
  5. 5.
    Uys CE (2006) Preparation and characterization of Pheroids. Department of Pharmacy, North-west University, PotchefstroomGoogle Scholar
  6. 6.
    Grobler, AF. Pharmaceutical applications of Pheroid™ technology, Pharmacy, North-West University, Potchefstroom, 2008Google Scholar
  7. 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 409:209–215CrossRefGoogle Scholar
  8. 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, NieuwoudtGoogle Scholar
  9. 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 83:373–378CrossRefGoogle Scholar
  10. 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 556:317–330CrossRefGoogle Scholar
  11. 11.
    Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70:1–20CrossRefGoogle Scholar
  12. 12.
    Hans M, Lowman A (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6:319–327CrossRefGoogle Scholar
  13. 13.
    Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4:145–160CrossRefGoogle Scholar
  14. 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;2011Google Scholar
  15. 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 48:112–118CrossRefGoogle Scholar
  16. 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 342:92–96CrossRefGoogle Scholar
  17. 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 10:313–325CrossRefGoogle Scholar
  18. 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 9:474–491CrossRefGoogle Scholar
  19. 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 6:557–563CrossRefGoogle Scholar
  20. 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 4:1787–1791CrossRefGoogle Scholar
  21. 21.
    Sollohub K, Cal K (2009) Spray drying technique: II. Current applications in pharmaceutical technology. J Pharm Sci 9999:1–11Google Scholar
  22. 22.
    Bernkop-Schnürch A, Dünnhaupt S (2012) Chitosan-based drug delivery systems. Eur J Pharm Biopharm 81:463–469CrossRefGoogle Scholar
  23. 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 5:854–862CrossRefGoogle Scholar
  24. 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 65:865–879CrossRefGoogle Scholar
  25. 25.
    Truong NP, Whittaker MR, Mak CW, Davis TP (2015) The importance of nanoparticle shape in cancer drug delivery. Expert Opin Drug Deliv 12:129–142CrossRefGoogle Scholar
  26. 26.
    Klang V, Valenta C (2011) Lecithin-based nanoemulsions. J Drug Deliv Sci Technol 21:55–76CrossRefGoogle Scholar
  27. 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 8:3651–3660CrossRefGoogle Scholar
  28. 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 5:281–285CrossRefGoogle Scholar
  29. 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 417:120–137CrossRefGoogle Scholar
  30. 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 20:4391–4399CrossRefGoogle Scholar
  31. 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 49:7850–7858CrossRefGoogle Scholar
  32. 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 42:152–162CrossRefGoogle Scholar
  33. 33.
    Leica EM Sample Preparation Contrasting. In: GmbH LM, editors. LEICA, Vienna, 2013Google Scholar
  34. 34.
    StainFile, Osmium Tetroxide 2015Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Madichaba P. Chelopo
    • 1
    • 2
    Email author
  • Lonji Kalombo
    • 1
  • James Wesley-Smith
    • 3
  • Anne Grobler
    • 2
  • Rose Hayeshi
    • 2
  1. 1.Polymers and CompositesCouncil for Scientific and Industrial Research, Materials Science and ManufacturingPretoriaSouth Africa
  2. 2.DST/NWU Preclinical Drug Development PlatformNorth-West UniversityPotchefstroomSouth Africa
  3. 3.DST/CSIR National Centre for Nanostructured MaterialsCouncil for Scientific and Industrial ResearchPretoriaSouth Africa

Personalised recommendations