PMID- 29408551
OWN - NLM
STAT- MEDLINE
DCOM- 20181002
LR  - 20181202
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 117
DP  - 2018 May 30
TI  - Dual dye in-vivo imaging of differentially charged PLGA carriers reveals 
      antigen-depot effect, leading to improved immune responses in preclinical models.
PG  - 88-97
LID - S0928-0987(18)30054-X [pii]
LID - 10.1016/j.ejps.2018.01.040 [doi]
AB  - The present in-vivo study investigated the behavior and performance of 
      differently charged poly(lactic‑co‑glycolic) acid microparticles (PLGA MP) as 
      vaccination platform. For this purpose, particles loaded with ovalbumin (OVA) as 
      model antigen were subcutaneously (s.c.) injected in SKH1 mice. The utilized SKH1 
      hairless mice exhibit a fully operative immune system and allow parallel imaging 
      investigations due to the lack of hair. Usage of this species enabled the 
      combination of two investigations within a single study protocol, namely 
      noninvasive in-vivo imaging and immune responses directed towards the antigen. 
      All treatments were well tolerated, no safety drop-outs occurred. The fate of the 
      model antigen OVA as well as the PLGA particles was monitored using a dual dye 
      approach (CF660C & DiR) by multispectral fluorescence imaging (msFI). A depot 
      effect for the OVA antigen adsorbed to the MP surface could be observed for the 
      positively charged MPs. The immune response against OVA was then analyzed. OVA 
      alone did not induce an immune response, whereas the positively charged as well 
      as the neutral MP induced a strong and consistent humoral immune response with a 
      clear favor of IgG1 over IgG2a subclass antibodies. In contrast, negatively 
      charged MP were not able to induce measurable antibody responses. Cellular immune 
      response was weak and inconsistent for all treated groups, which verifies 
      previous in-vitro results conducted with the herein described microparticulate 
      antigen platform. In conclusion, the characterization of the in-vivo performance 
      yielded valuable information about antigen and carrier fate after application. 
      The presented adjuvant platform is capable of inducing strong T(H)2 dominated 
      immune responses characterized by enhanced IgG1 subclass titers which are 
      critical for vaccines aimed at promoting induction of neutralizing antibodies.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Riehl, Markus
AU  - Riehl M
AD  - Institute of Pharmacy, Faculty I of Natural Sciences, Martin-Luther-University 
      Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany; 
      Department Pharmaceutical Technologies, Merck KGaA, Frankfurter Strasse 250, 64293 
      Darmstadt, Germany.
FAU - Harms, Meike
AU  - Harms M
AD  - Department Pharmaceutical Technologies, Merck KGaA, Frankfurter Strasse 250, 64293 
      Darmstadt, Germany.
FAU - Lucas, Henrike
AU  - Lucas H
AD  - Institute of Pharmacy, Faculty I of Natural Sciences, Martin-Luther-University 
      Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany.
FAU - Ebensen, Thomas
AU  - Ebensen T
AD  - Department of Vaccinology and Applied Microbiology, Helmholtz Centre for 
      Infection Research, Inhoffenstr 7, 38124 Braunschweig, Germany.
FAU - Guzman, Carlos A
AU  - Guzman CA
AD  - Department of Vaccinology and Applied Microbiology, Helmholtz Centre for 
      Infection Research, Inhoffenstr 7, 38124 Braunschweig, Germany.
FAU - Mader, Karsten
AU  - Mader K
AD  - Institute of Pharmacy, Faculty I of Natural Sciences, Martin-Luther-University 
      Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany. 
      Electronic address: Karsten.Maeder@pharmazie.uni-halle.de.
LA  - eng
PT  - Journal Article
DEP - 20180213
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antigens)
RN  - 0 (Carbocyanines)
RN  - 0 (Cytokines)
RN  - 0 (Drug Carriers)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Immunoglobulin G)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 40957-95-7 (3,3'-dioctadecylindocarbocyanine)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Adjuvants, Immunologic/*administration & dosage
MH  - Animals
MH  - Antigens/*administration & dosage
MH  - Carbocyanines/administration & dosage
MH  - Cytokines/immunology
MH  - Drug Carriers/*administration & dosage
MH  - Drug Evaluation, Preclinical
MH  - Fluorescent Dyes/administration & dosage
MH  - Immunoglobulin G/immunology
MH  - Lactic Acid/*administration & dosage
MH  - Male
MH  - Mice, Hairless
MH  - Ovalbumin/*administration & dosage
MH  - Polyglycolic Acid/*administration & dosage
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
OTO - NOTNLM
OT  - Charged microparticles
OT  - DiR
OT  - Fluorescence imaging
OT  - Ovalbumin
OT  - PLGA
OT  - Vaccination
EDAT- 2018/02/07 06:00
MHDA- 2018/10/03 06:00
CRDT- 2018/02/07 06:00
PHST- 2017/10/06 00:00 [received]
PHST- 2018/01/23 00:00 [revised]
PHST- 2018/01/25 00:00 [accepted]
PHST- 2018/02/07 06:00 [pubmed]
PHST- 2018/10/03 06:00 [medline]
PHST- 2018/02/07 06:00 [entrez]
AID - S0928-0987(18)30054-X [pii]
AID - 10.1016/j.ejps.2018.01.040 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2018 May 30;117:88-97. doi: 10.1016/j.ejps.2018.01.040. Epub 
      2018 Feb 13.