Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers

Fan Zhang, Elizabeth Nance, Zhi Zhang, Venkatasai Jasty, Siva P. Kambhampati, Manoj K. Mishra, Irina Burd, Roberto Romero, Sujatha Kannan, Rangaramanujam M. Kannan

Research output: Contribution to journalArticlepeer-review

Abstract

Cerebral Palsy (CP) is a chronic childhood disorder with limited therapeutic options. Maternal intrauterine inflammation/infection is a major risk factor in the pathogenesis of CP. In pre-clinical models, dendrimer-based therapies are viable in postnatal period, attenuating inflammation and improving motor function in vivo. However, treatment to the mother, in the prenatal period, may provide the possibility of preventing/resolving inflammation at early stages. Towards this goal, we used a maternal intrauterine inflammation-induced rabbit model of CP to study fetal-maternal transport and neuroinflammation targeting of intra-amniotically administrated dendrimers with neutral/anionic surface functionality. Our study suggested both hydroxyl-terminated ‘neutral’ (D-OH) and carboxyl-terminated ‘anionic’ (D-COOH) Polyamidoamine (PAMAM) dendrimers were absorbed by fetuses and demonstrated bi-directional transport between fetuses and mother. D-OH was more effective in crossing the fetal blood-brain barrier, and targeting activated microglia. The cell-specific targeting was associated with the extent of microglia activation. This study demonstrated intra-amniotically administered hydroxyl PAMAM dendrimers could be an effective drug delivery vehicle for targeting fetal inflammation and preventing subsequent neurologic injury associated with chorioamnionitis.

Original languageEnglish (US)
Pages (from-to)61-70
Number of pages10
JournalJournal of Controlled Release
Volume237
DOIs
StatePublished - Sep 10 2016

Keywords

  • Blood-placental barrier
  • Dendrimer
  • Intra-amniotic delivery
  • Microglia
  • Neuroinflammation
  • Surface functionality

ASJC Scopus subject areas

  • Pharmaceutical Science

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