Multiple Lipid Nanoparticles (MLN), a New Generation of Lipid Nanoparticles for Drug Delivery Systems: Lamivudine-MLN Experimental Design

Pharm Res. 2017 Jun;34(6):1204-1216. doi: 10.1007/s11095-017-2136-0. Epub 2017 Mar 17.


Purpose: An optimized methodology for the development of a new generation of lipid nanoparticles, the multiple lipid nanoparticles (MLN) is described. MLN have characteristics between nanostructured lipid carriers (NLC) and multiple emulsions (W/O/W), but without the outer aqueous phase.

Methods: The production is based on a hot homogenization method combined with high shear and ultrasonication. The antiretroviral agent lamivudine (3TC), was loaded in the MLN. For comparison purposes, NLC-3TC formulation was also developed and physico-chemically characterized by the same parameters as MLN-3TC. The development and optimization of MLN and NLC formulations were supported by a Quality by Design (QbD) approach.

Results: The MLN-3TC formulation exhibited a size of about 450 nm, polydispersity <0.3 and negative zeta potential > -20 mV. Furthermore, the morphology assessed by TEM showed a structure with multiples aqueous vacuoles. MLN-3TC was physically stable for at least 45 days, had low cytotoxicity and drug release studies showed a sustained and controlled release of 3TC under gastric and plasma-simulated conditions (at pH 7.4 for about 45 h).

Conclusions: The optimized formulations present suitable profiles for oral administration. Overall, the results reveal that MLN present higher loading capacity and storage stability than NLC.

Keywords: MLN; NLC; lamivudine (3TC); lipid nanoparticles; quality by design (QbD).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anti-Retroviral Agents / chemistry
  • Anti-Retroviral Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Drug Carriers
  • Drug Compounding
  • Drug Liberation
  • Drug Stability
  • Emulsions
  • Humans
  • Lamivudine / chemistry
  • Lamivudine / pharmacology*
  • Lipids / chemistry*
  • Nanoparticles / chemistry*
  • Particle Size
  • Research Design
  • Surface Properties


  • Anti-Retroviral Agents
  • Drug Carriers
  • Emulsions
  • Lipids
  • Lamivudine