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



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.



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).



The optimized formulations present suitable profiles for oral administration. Overall, the results reveal that MLN present higher loading capacity and storage stability than NLC.
UCIBIO/REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.|Core of Medicine and Corelated Quality Control - NCQMC Department of Pharmaceutical Sciences,, Federal University of Pernambuco, Rua Arthur de Sá, s/n, Cidade Universitária, Recife, PE, 50740-521, Brazil.
Suellen M T
SMT
Cavalcanti
UCIBIO/REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. cdnunes@ff.up.pt.
Cláudia
0000-0002-1502-3710
C
Nunes
UCIBIO/REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
Sofia A C
SAC
Lima
Core of Medicine and Corelated Quality Control - NCQMC Department of Pharmaceutical Sciences,, Federal University of Pernambuco, Rua Arthur de Sá, s/n, Cidade Universitária, Recife, PE, 50740-521, Brazil.
José L
JL
Soares-Sobrinho
UCIBIO/REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
Salette
S
Reis
D000284:Administration, Oral; D044966:Anti-Retroviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions; D006801:Humans; D019259:Lamivudine / Q000737:chemistry / Q000494:pharmacology*; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012107:Research Design; D013499:Surface Properties
D044966:Anti-Retroviral Agents; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D019259:Lamivudine
MLN; NLC; lamivudine (3TC); lipid nanoparticles; quality by design (QbD)