PMID- 17692440
OWN - NLM
STAT- MEDLINE
DCOM- 20071108
LR  - 20070907
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 25
IP  - 37-38
DP  - 2007 Sep 17
TI  - Diphtheria toxoid-containing microparticulate powder formulations for pulmonary 
      vaccination: preparation, characterization and evaluation in guinea pigs.
PG  - 6818-29
AB  - In this study, the potential of N-Trimethyl chitosan (TMC, degree of 
      quaternization 50%) and dextran microparticles for pulmonary delivery of 
      diphtheria toxoid (DT) was investigated. The antigen-containing microparticles 
      were prepared by drying of an aqueous solution of polymer and DT through a 
      supercritical fluid (SCF) spraying process. The median volume diameter of the dry 
      particles, as determined by laser diffraction analysis, was between 2 and 3 
      microm and the fine particle mass fractions smaller than 5 microm, as determined 
      by cascade impactor analysis, were 35 and 56% for the dextran and TMC 
      formulations, respectively. The water content of the particles as measured by 
      Karl-Fischer titration was 2-3% (w/w). Pulmonary immunization with DT-TMC 
      microparticles containing 2 or 10 Lf of DT resulted in a strong immunological 
      response as reflected by the induction of IgM, IgG, IgG subclasses (IgG1 and 
      IgG2) antibodies as well as neutralizing antibody titers comparable to or 
      significantly higher than those achieved after subcutaneous (SC) administration 
      of alum-adsorbed DT (2 Lf). Moreover, the IgG2/IgG1 ratio after pulmonary 
      immunization with DT-TMC microparticles was substantially higher as compared to 
      SC administered alum-adsorbed DT. In contrast, pulmonarily administered 
      DT-dextran particles were poorly immunogenic. Among the tested formulations only 
      pulmonarily administered DT-containing TMC microparticles induced detectable 
      pulmonary secretory IgA levels. In conclusion, in this paper it is demonstrated 
      that TMC microparticles are a potent new delivery system for pulmonary 
      administered DT antigen.
FAU - Amidi, Maryam
AU  - Amidi M
AD  - Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, 
      Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
FAU - Pellikaan, Hubert C
AU  - Pellikaan HC
FAU - Hirschberg, Hoang
AU  - Hirschberg H
FAU - de Boer, Anne H
AU  - de Boer AH
FAU - Crommelin, Daan J A
AU  - Crommelin DJ
FAU - Hennink, Wim E
AU  - Hennink WE
FAU - Kersten, Gideon
AU  - Kersten G
FAU - Jiskoot, Wim
AU  - Jiskoot W
LA  - eng
PT  - Journal Article
DEP - 20070618
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Diphtheria Toxoid)
RN  - 0 (Diphtheria-Tetanus-Pertussis Vaccine)
RN  - 0 (Immunoglobulins)
RN  - 0 (N-trimethyl chitosan chloride)
RN  - 0 (Powders)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - Animals
MH  - Chitosan
MH  - Diphtheria Toxoid/*immunology
MH  - Diphtheria-Tetanus-Pertussis Vaccine/immunology
MH  - Female
MH  - Guinea Pigs
MH  - Immunoglobulins/blood/immunology
MH  - Lung/*immunology
MH  - Male
MH  - Microscopy, Electron, Scanning
MH  - Nanoparticles/ultrastructure
MH  - Particle Size
MH  - Powders
MH  - *Vaccination
EDAT- 2007/08/19 09:00
MHDA- 2007/11/09 09:00
CRDT- 2007/08/19 09:00
PHST- 2007/02/07 00:00 [received]
PHST- 2007/05/07 00:00 [revised]
PHST- 2007/05/30 00:00 [accepted]
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2007/11/09 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
AID - S0264-410X(07)00656-1 [pii]
AID - 10.1016/j.vaccine.2007.05.064 [doi]
PST - ppublish
SO  - Vaccine. 2007 Sep 17;25(37-38):6818-29. doi: 10.1016/j.vaccine.2007.05.064. Epub 
      2007 Jun 18.