PMID- 31437396
OWN - NLM
STAT- MEDLINE
DCOM- 20200617
LR  - 20200617
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 16
IP  - 10
DP  - 2019 Oct 7
TI  - Scale-Independent Microfluidic Production of Cationic Liposomal Adjuvants and 
      Development of Enhanced Lymphatic Targeting Strategies.
PG  - 4372-4386
LID - 10.1021/acs.molpharmaceut.9b00730 [doi]
AB  - Cationic liposomes prepared from dimethyldioctadecylammonium bromide (DDAB) and 
      trehalose 6,6'-dibehenate (TDB) are strong liposomal adjuvants. As with many 
      liposome formulations, within the laboratory DDAB:TDB is commonly prepared by the 
      thin-film method, which is difficult to scale-up and gives high batch-to-batch 
      variability. In contrast, controllable technologies such as microfluidics offer 
      robust, continuous, and scale-independent production. Therefore, within this 
      study, we have developed a microfluidic production method for cationic liposomal 
      adjuvants that is scale-independent and produces liposomal adjuvants with 
      analogous biodistribution and immunogenicity compared to those produced by the 
      small-scale lipid hydration method. Subsequently, we further developed the 
      DDAB:TDB adjuvant system to include a lymphatic targeting strategy using 
      microfluidics. By exploiting a biotin-avidin complexation strategy, we were able 
      to manipulate the pharmacokinetic profile and enhance targeting and retention of 
      DDAB:TDB and antigen within the lymph nodes. Interestingly, redirecting these 
      cationic liposomal adjuvants did not translate into notably improved vaccine 
      efficacy.
FAU - Roces, Carla B
AU  - Roces CB
AD  - Strathclyde Institute of Pharmacy and Biomedical Sciences , University of 
      Strathclyde , Glasgow G4 0RE , Scotland.
FAU - Khadke, Swapnil
AU  - Khadke S
AD  - Strathclyde Institute of Pharmacy and Biomedical Sciences , University of 
      Strathclyde , Glasgow G4 0RE , Scotland.
FAU - Christensen, Dennis
AU  - Christensen D
AD  - Center for Vaccine Research , Statens Serum Institut , DK-2300 Copenhagen , 
      Denmark.
FAU - Perrie, Yvonne
AU  - Perrie Y
AUID- ORCID: 0000-0001-8497-2541
AD  - Strathclyde Institute of Pharmacy and Biomedical Sciences , University of 
      Strathclyde , Glasgow G4 0RE , Scotland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190906
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Cations)
RN  - 0 (Liposomes)
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 0 (Tuberculosis Vaccines)
RN  - 251IW5I21C (dimethyldioctadecylammonium)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage/*chemistry
MH  - Animals
MH  - Antigens, Bacterial/administration & dosage/immunology
MH  - Cations/*chemistry
MH  - Female
MH  - Immunization
MH  - Liposomes/administration & dosage/*chemistry
MH  - Lymph Nodes/*drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - *Microfluidics
MH  - Quaternary Ammonium Compounds/*chemistry
MH  - Tissue Distribution
MH  - Tuberculosis/immunology/prevention & control
MH  - Tuberculosis Vaccines/*administration & dosage/immunology/pharmacokinetics
OTO - NOTNLM
OT  - cationic liposomes
OT  - lymphatic targeting
OT  - manufacture
OT  - microfluidics
OT  - vaccine adjuvants
EDAT- 2019/08/23 06:00
MHDA- 2020/06/18 06:00
CRDT- 2019/08/23 06:00
PHST- 2019/08/23 06:00 [pubmed]
PHST- 2020/06/18 06:00 [medline]
PHST- 2019/08/23 06:00 [entrez]
AID - 10.1021/acs.molpharmaceut.9b00730 [doi]
PST - ppublish
SO  - Mol Pharm. 2019 Oct 7;16(10):4372-4386. doi: 10.1021/acs.molpharmaceut.9b00730. 
      Epub 2019 Sep 6.