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Nanoparticulate drug delivery systems offer great promise in addressing challenges of drug toxicity, poor
bioavailability and non-specificity for a number of drugs. Much progress has been reported for nano drug
delivery systems for intravenous administration, however very little is known about the effects of orally
administered nanoparticles. Furthermore, the development of nanoparticulate systems necessitates a
thorough understanding of the biological response post exposure. This study aimed to elucidate the in vivo
uptake of chitosan and polyethylene glycol (PEG) coated Poly, DL, lactic-co-glycolic Acid (PLGA) nanoparticles
and the immunological response within 24 h of oral and peritoneal administration. These PLGA nanoparticles
were administered orally and peritoneally to female Balb/C mice, they were taken up by macrophages of the
peritoneum. When these particles were fluorescently labelled, intracellular localisation was observed. The
expression of pro-inflammatory cytokines IL-2, IL-6, IL-12p70 and TNF-α in plasma and peritoneal lavage was
found to remain at low concentration in PLGA nanoparticles treated mice as well as ZnO nanoparticles during
the 24 hour period. However, these were significantly increased in lipopolysaccharide (LPS) treated mice. Of
these pro-inflammatory cytokines, IL-6 and IL-12p70 were produced at the highest concentration in the
positive control group. The anti-inflammatory cytokines IL-10 and chemokines INF-γ, IL-4, IL-5 remained at
normal levels in PLGA treated mice. IL-10 and INF-γ were significantly increased in LPS treated mice. MCP-1
was found to be significantly produced in all groups in the first hours, except the saline treated mice. These
results provide the first report to detail the induction of cytokine production by PLGA nanoparticles
engineered for oral applications. |
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