PMID- 25957906
OWN - NLM
STAT- MEDLINE
DCOM- 20160321
LR  - 20220316
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 210
DP  - 2015 Jul 28
TI  - Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A 
      quality-by-design approach.
PG  - 48-57
LID - S0168-3659(15)00302-8 [pii]
LID - 10.1016/j.jconrel.2015.05.004 [doi]
AB  - The purpose of this study was to design a novel and versatile adjuvant intended 
      for mucosal vaccination based on biodegradable poly(DL-lactic-co-glycolic acid) 
      (PLGA) nanoparticles (NPs) modified with the cationic surfactant 
      dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator 
      trehalose-6,6'-dibehenate (TDB) (CAF01) to tailor humoral and cellular immunity 
      characterized by antibodies and Th1/Th17 responses. Such responses are important 
      for the protection against diseases caused by intracellular bacteria such as 
      Chlamydia trachomatis and Mycobacterium tuberculosis. The hybrid NPs were 
      engineered using an oil-in-water single emulsion method and a quality-by-design 
      approach was adopted to define the optimal operating space (OOS). Four critical 
      process parameters (CPPs) were identified, including the acetone concentration in 
      the water phase, the stabilizer [polyvinylalcohol (PVA)] concentration, the 
      lipid-to-total solid ratio, and the total concentration. The CPPs were linked to 
      critical quality attributes consisting of the particle size, polydispersity index 
      (PDI), zeta-potential, thermotropic phase behavior, yield and stability. A 
      central composite face-centered design was performed followed by multiple linear 
      regression analysis. The size, PDI, enthalpy of the phase transition and yield 
      were successfully modeled, whereas the models for the zeta-potential and the 
      stability were poor. Cryo-transmission electron microscopy revealed that the main 
      structural effect on the nanoparticle architecture is caused by the use of PVA, 
      and two different morphologies were identified: i) A PLGA core coated with one or 
      several concentric lipid bilayers, and ii) a PLGA nanoshell encapsulating lipid 
      membrane structures. The optimal formulation, identified from the OOS, was 
      evaluated in vivo. The hybrid NPs induced antibody and Th1/Th17 immune responses 
      that were similar in quality and magnitude to the response induced by DDA/TDB 
      liposomes, showing that the adjuvant properties of DDA/TDB are maintained in the 
      PLGA hybrid matrix. This study demonstrates the complexity of formulation design 
      for the engineering of a hybrid lipid-polymer nanoparticle adjuvant.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Rose, Fabrice
AU  - Rose F
AD  - Department of Pharmacy, Faculty of Health and Medical Sciences, University of 
      Copenhagen Universitetsparken 2, DK-2100 Copenhagen O, Denmark.
FAU - Wern, Jeanette Erbo
AU  - Wern JE
AD  - Department of Infectious Disease Immunology, Chlamydia Vaccine Research, Statens 
      Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
FAU - Ingvarsson, Pall Thor
AU  - Ingvarsson PT
AD  - Department of Pharmacy, Faculty of Health and Medical Sciences, University of 
      Copenhagen Universitetsparken 2, DK-2100 Copenhagen O, Denmark.
FAU - van de Weert, Marco
AU  - van de Weert M
AD  - Department of Pharmacy, Faculty of Health and Medical Sciences, University of 
      Copenhagen Universitetsparken 2, DK-2100 Copenhagen O, Denmark.
FAU - Andersen, Peter
AU  - Andersen P
AD  - Department of Infectious Disease Immunology, Chlamydia Vaccine Research, Statens 
      Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
FAU - Follmann, Frank
AU  - Follmann F
AD  - Department of Infectious Disease Immunology, Chlamydia Vaccine Research, Statens 
      Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
FAU - Foged, Camilla
AU  - Foged C
AD  - Department of Pharmacy, Faculty of Health and Medical Sciences, University of 
      Copenhagen Universitetsparken 2, DK-2100 Copenhagen O, Denmark. Electronic 
      address: camilla.foged@sund.ku.dk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150506
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Glycolipids)
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 0 (Surface-Active Agents)
RN  - 0 (trehalose 6,6'-dibehenate)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 251IW5I21C (dimethyldioctadecylammonium)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Adjuvants, Immunologic/*chemistry
MH  - Drug Design
MH  - Glycolipids/*chemistry
MH  - Lactic Acid/*chemistry
MH  - Microscopy, Electron, Transmission
MH  - Nanoparticles/*chemistry/ultrastructure
MH  - Polyglycolic Acid/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Quaternary Ammonium Compounds/chemistry
MH  - Surface-Active Agents/chemistry
OTO - NOTNLM
OT  - Adjuvant
OT  - Dimethyldioctadecylammonium (DDA)
OT  - Drug delivery
OT  - Nanomedicine
OT  - Nanoparticles
OT  - PLGA
OT  - Quality-by-design (QbD)
OT  - Trehalose 6,6-dibehenate
OT  - Vaccine
EDAT- 2015/05/11 06:00
MHDA- 2016/03/22 06:00
CRDT- 2015/05/11 06:00
PHST- 2015/05/04 00:00 [received]
PHST- 2015/05/05 00:00 [accepted]
PHST- 2015/05/11 06:00 [entrez]
PHST- 2015/05/11 06:00 [pubmed]
PHST- 2016/03/22 06:00 [medline]
AID - S0168-3659(15)00302-8 [pii]
AID - 10.1016/j.jconrel.2015.05.004 [doi]
PST - ppublish
SO  - J Control Release. 2015 Jul 28;210:48-57. doi: 10.1016/j.jconrel.2015.05.004. 
      Epub 2015 May 6.