Skip to main content

Advertisement

SpringerLink
Log in

Effect of pH and electrolytes on the colloidal stability of stearic acid–based lipid nanoparticles

  • Research Paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

Stearic acid–based solid lipid nanoparticles, stabilised with Tween® 20, were synthesised using a microwave-assisted microemulsion technique and their stability was tested in simulated blood plasma, several liquids mimicking gastrointestinal fluids and solutions containing different electrolyte compositions and pH levels. It was discovered that simulated blood plasma had a stabilising effect on the particles, as did simulated saliva and intestinal fluid, which was due to hydration forces, facilitated by the presence of hydrated cations. It was determined that the hydration stabilisation was pH dependent, with highly acidic conditions depriving the solid lipid nanoparticles of the negative charge required for the cations to hydrate the surface. In environments lacking hydrated cations, the particles were predominately reliant on steric stabilisation and were particularly susceptible to pH extremes due to hydrolysis/oxidation of the Tween® 20 layer. The results suggest that the SLNs have potential as a systemic drug carrier, as the physicochemical conditions of blood provide a stabilising environment that inhibits particle growth.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

BIC:

Brookhaven Instruments Corporation

ELS:

Electrophoretic light scattering

PCS:

Photon correlation spectroscopy

RTP:

Research Training Program

SBF(s):

Simulated body fluid(s)

SGJ:

Simulated gastric juice

SIF:

Simulated intestinal fluid

SLN(s):

Solid lipid nanoparticle(s)

SS:

Simulated saliva

References

  • Agha-Hosseini F, Dizgah IM, Amirkhani S (2006) The composition of unstimulated whole saliva of healthy dental students. J Contemp Dent Pract 7:104–111

    Google Scholar 

  • Bates TR, Nightingdale CH, Dixon E (1973) Kinetics of hydrolysis of polyoxyethylene (20) sorbitan fatty acid ester surfactants. J Pharm Pharmacol 25:470–477

    Article  CAS  Google Scholar 

  • Das S, Chaudhury A (2011) Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech 12:62–76

    Article  CAS  Google Scholar 

  • Elsabahy M, Wooley KL (2012) Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev 41:2545–2561

    Article  CAS  Google Scholar 

  • Freitas C (1999) Stability determination of solid lipid nanoparticles (SLN TM) in aqueous dispersion after addition of electrolyte. J Microencapsul 16:59–71

    Article  CAS  Google Scholar 

  • Freitas C, Müller RH (1999) Correlation between long-term stability of solid lipid nanoparticles (SLN™) and crystallinity of the lipid phase. Eur J Pharm Biopharm 47:125–132

    Article  CAS  Google Scholar 

  • Guo X, Szoka FC (2001) Steric stabilization of Fusogenic liposomes by a low-pH sensitive PEG−Diortho Ester−lipid conjugate. Bioconjug Chem 12:291–300

    Article  CAS  Google Scholar 

  • He C, Hu Y, Yin L, Tang C, Yin C (2010) Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 31:3657–3666

    Article  CAS  Google Scholar 

  • Heurtault B, Saulnier P, Pech B, Proust J-E, Benoit J-P (2003) Physico-chemical stability of colloidal lipid particles. Biomaterials 24:4283–4300

    Article  CAS  Google Scholar 

  • Lindahl A, Ungell A-L, Knutson L, LennernÄS H (1997) Characterization of fluids from the stomach and proximal jejunum in men and women. Pharm Res 14:497–502

    Article  CAS  Google Scholar 

  • López-León T, Santander-Ortega MJ, Ortega-Vinuesa JL, Bastos-González D (2008) Hofmeister effects in colloidal systems: influence of the surface nature. J Phys Chem C 112:16060–16069

    Article  Google Scholar 

  • Marques MR, Loebenberg R, Almukainzi M (2011) Simulated biological fluids with possible application in dissolution testing. Dissolut Technol 18:15–28

    Article  CAS  Google Scholar 

  • Mccance R (1938) The effect of salt deficiency in man on the volume of the extracellular fluids, and on the composition of sweat, saliva, gastric juice and cerebrospinal fluid. J Physiol 92:208–218

    Article  CAS  Google Scholar 

  • Mehnert W, Mäder K (2001) Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev 47:165–196

    Article  CAS  Google Scholar 

  • Morachis JM, Mahmoud EA, Almutairi A (2012) Physical and chemical strategies for therapeutic delivery by using polymeric nanoparticles. Pharmacol Rev 64:505–519

    Article  CAS  Google Scholar 

  • Mukherjee S, Ray S, Thakur RS (2009) Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci 71:349–358

    Article  CAS  Google Scholar 

  • Müller RH, Mäder K, Gohla S (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery–a review of the state of the art. Eur J Pharm Biopharm 50:161–177

    Article  Google Scholar 

  • Oyane A, Kim HM, Furuya T, Kokubo T, Miyazaki T, Nakamura T (2003) Preparation and assessment of revised simulated body fluids. J Biomed Mater Res A 65:188–195

    Article  Google Scholar 

  • Peula-García JM, Ortega-Vinuesa JL, Bastos-González D (2010) Inversion of Hofmeister series by changing the surface of colloidal particles from hydrophobic to hydrophilic. J Phys Chem C 114:11133–11139

    Article  Google Scholar 

  • Schwarz C (1999) Solid lipid nanoparticles (SLN) for controlled drug delivery II. Drug incorporation and physicochemical characterization. J Microencapsul 16:205–213

    Article  CAS  Google Scholar 

  • Shah R (2016) Microwave-assisted Production of Solid Lipid Nanoparticles. PhD Thesis, Swinburne University of Technology

  • Shah RM, Malherbe F, Eldridge D, Palombo EA, Harding IH (2014) Physicochemical characterization of solid lipid nanoparticles (SLNs) prepared by a novel microemulsion technique. J Colloid Interface Sci 428:286–294

    Article  CAS  Google Scholar 

  • Shah R, Eldridge D, Palombo E, Harding I (2015) Lipid nanoparticles: production, characterization and stability. Springer

  • Shah RM, Bryant G, Taylor M, Eldridge DS, Palombo EA, Harding IH (2016a) Structure of solid lipid nanoparticles produced by a microwave-assisted microemulsion technique. RSC Adv 6:36803–36810

    Article  CAS  Google Scholar 

  • Shah RM, Eldridge DS, Palombo EA, Harding IH (2016b) Microwave-assisted formulation of solid lipid nanoparticles loaded with non-steroidal anti-inflammatory drugs. Int J Pharm 515:543–554

    Article  CAS  Google Scholar 

  • Shah RM, Eldridge DS, Palombo EA, Harding IH (2017) Microwave-assisted microemulsion technique for production of miconazole nitrate- and econazole nitrate-loaded solid lipid nanoparticles. Eur J Pharm Biopharm 117:141–150

    Article  CAS  Google Scholar 

  • Shah RM, Mata JP, Bryant G, De Campo L, Ife A, Karpe AV, Jadhav SR, Eldridge DS, Palombo EA, Harding IH (2018) Structure analysis of solid lipid nanoparticles for drug delivery: a combined USANS/SANS Study [Forthcoming]. Part Part Syst Charact 1800359

  • Shaw DJ (1992) Introduction to colloid and surface chemistry. Butterworth-Heinemann Ltd, Oxford

    Google Scholar 

  • Tadros TF (2015) Interfacial phenomena and colloid stability: basic principles. De Gruyter, Berlin

    Google Scholar 

  • Zhang L, Yadav S, Demeule B, Wang YJ, Mozziconacci O, SchӦneich C (2017) Degradation mechanisms of polysorbate 20 differentiated by 18O-labeling and mass spectrometry. Pharm Res 34:84–100

    Article  CAS  Google Scholar 

  • Zimmermann E, Müller RH (2001) Electrolyte-and pH-stabilities of aqueous solid lipid nanoparticle (SLN™) dispersions in artificial gastrointestinal media. Eur J Pharm Biopharm 52:203–210

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are thankful to Savithri Galappathie who prepared several solutions that were used throughout the course of this research.

Funding

This study received financial support from the Australian Government’s Research Training Program (RTP).

Author information

Authors and Affiliations

  1. Department of Chemistry and Biotechnology, Swinburne University of Technology, PO Box 218, Hawthorn, Victoria, 3122, Australia

    Alexander F. Ife, Ian H. Harding, Rohan M. Shah, Enzo A. Palombo & Daniel S. Eldridge

Authors
  1. Alexander F. Ife
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ian H. Harding
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rohan M. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Enzo A. Palombo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel S. Eldridge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexander F. Ife.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ife, A.F., Harding, I.H., Shah, R.M. et al. Effect of pH and electrolytes on the colloidal stability of stearic acid–based lipid nanoparticles. J Nanopart Res 20, 318 (2018). https://doi.org/10.1007/s11051-018-4425-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-018-4425-x

Keywords

Search

Navigation