1. Surface-functionalized, pH-responsive poly(lactic-co-glycolic acid)- based microparticles for intranasal vaccine delivery: Effect of surface modification with chitosan and mannan
Jihui Lee
DEC 13, 2016

2. PLGA Surface modification for adjuvant effects
pH dependent release rate (NaHCO3)
L:G=75:25, MW : 13kDa
protect antigen from protease degradation
deliver antigen to antigen presenting cells (APCs)
Double emulsion: sustained release(kinetics), can’t lypholize (many pockets in plga)
Mn: mannose receptor ligand

3. PLGA protect antigen from protease degradation
deliver antigen to antigen presenting cells (APCs)
Double emulsion: sustained release(kinetics), can’t lypholize (many pockets in plga)
Mn: mannose receptor ligand

4. PLGA Chitosan ZETA: PLGA size:773nm SEM: modification is bigger
Cs:+, MANNAN:- charge

5. In vitro release rate FITC-HSC
Surface modification-release rate, antigenicity
How they control ph of body?
Ph7.4 fast due to nahco3+proton=co2-rupture

6. In vitro uptake efficiency
Measure FITC-HSA
Cs content (+) make better uptake
MN increase in 12345
5: macrophage pre-treated with mannose for 30min

7. Intracellular, in vitro release rate
FITC-HSC
PLGA,MN:faster, Intra cellular is similar with ph 5-6 (occurs in late endosome, lysosome)
CS:slower, Similar with ph 7.4(occurs in cytoplasm)

8. In vivo release rate
AFTER 10min, Plga 54%, MN 60% REMAIN IN NASAL CAVITY
After 1 hrm Cs 33%,, cs-MN remain 29% (longer residence time)
CS:Mucoadhesive property
Extended time-facilitate penetration of microparticles into sub-mucosa

9. In vivo release rate
Rat ELISA: Measure serum specific anti-Hbsag igG ab level
0.3.6week administration (intranasaly)
except Alum:0,3 week(subcutaneously)
At 8weeks, alum is high
At16 weeks, cs is highest
Cs:improve penetration and uptake of microparicle
CS Sustain release: prolonged ag presentation, lead powerful immune response
Cs-ms:combine release pattern, fast in endo/slow in cytoplasm-stronger immune response

10. Hydrodynamic size with zetasizer?
pH control in body?
FITC-HSA in stead of HBsAg.
Release rate & immune response