Non-Invasive Brain Delivery of G4 70/30 PAMAM Dendrimers via the Intranasal Route

TL;DR

This study shows that G4 70/30 PAMAM dendrimers can safely and effectively deliver to the brain via the nose, offering a new way to treat neurological disorders.

Contribution

Demonstrates the safety and CNS-targeting ability of G4 70/30 PAMAM dendrimers via intranasal delivery in mice.

Findings

G4 70/30 PAMAM dendrimers accumulated significantly in the brain after intranasal administration.

No toxicity was observed in major organs like lungs, liver, and kidneys.

Male mice showed higher brain fluorescence intensity compared to females.

Abstract

Effective treatment
of neurological disorders remains a major clinical
challenge due to the restrictive nature of the blood–brain
barrier (BBB), which limits the entry of most therapeutic agents into
the central nervous system (CNS). In this study, we investigated the
in vivo biodistribution, safety, and CNS targeting ability of fourth
generation (G4) PAMAM dendrimers, containing 70% hydroxyl and 30%
amine surface groups (G4 70/30) following intranasal administration
in C57BL/6J mice. Male and female mice were administered daily intranasal
doses of Cy5.5-labeled G4 70/30 PAMAM dendrimers for 4 weeks, while
control animals received Hank’s balanced salt solution (HBSS;
Gibco, Waltham, MA, USA). Whole-body fluorescence imaging was conducted
weekly to assess biodistribution, followed by organ extraction and
fluorescence microscopy to evaluate tissue-level accumulation. The
results revealed substantial accumulation of dendrimers in the brain,
with no signs of toxicity in major organs including the lungs, livers,
and kidneys. Notably, male mice exhibited significantly higher fluorescent
intensity in the brain compared to females. These findings support
the safety and effectiveness of G4 70/30 PAMAM dendrimers for intranasal
delivery and highlight their potential as carriers for CNS-targeted
therapies, including drugs and nucleic acids, in the treatment of
neurological disorders.

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