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Polyamidoamine (PAMAM) dendrimers are efficient drug carriers. The presence of a physiological pathway for nasal brain transport provides a potential path for direct brain-targeted delivery of dendrimer nanocomposites. In this study, we synthesized PAMAM dendrimer composites with a nanoscale size; the particle size of PAE (Paeonol)/mPEG (the heterofunctional PEG polymer with a methoxy)-PAMAM G5.NHAc and mPEG-PAMAM G5.NH₂-FITC were 72.41 ± 11.58 nm and 96.51 ± 7.77 nm, and the zeta potential of PAE/mPEG-PAMAM G5.NHAc and mPEG-PAMAM G5.NH₂-FITC were + 0.57 ± 0.11 mv and + 9.60 ± 0.41 mv, respectively. The EE% and DL% of PAE in PAE/mPEG-PAMAM G5.NHAc were 53.77% and 13.92%, respectively. PAE/mPEG-PAMAM G5.NHAc/DGG ionic-sensitive in situ gel was prepared, the viscosity of solution and gel state were 112 ± 3.2 mPa and 1403 ± 38.5 mPa, respectively. The in vitro goat mucoadhesive strength of the gel was 4763.36 ± 85.39 dyne/cm². In situ gel system was proven to be a non-Newtonian pseudo-plastic fluid with shear thinning, thixotropy and yield stress. The optimal model of PAE released from PAE/mPEG-PAMAM G5.NHAc and PAE/mPEG-PAMAM G5.NHAc/DGG were the Higuchi equation and the Korsmeyer-Peppas equation, respectively. The cytotoxicity of the nanocomposites showed a concentration-dependence, and the cell viabilities of PAE/mPEG-PAMAM G5.NHAc were both higher than 95% between 0.0001 μM and 10 μM. mPEG-PAMAM G5.NH₂-FITC was efficiently taken up by cells and exhibited strong fluorescence in the cytoplasm and nucleus. Significant accumulation of nanocomposites was observed in the brain after administration of the in situ gel group, and maximum accumulation was reached at 12 h. A small amount of accumulation was observed in the nanocomposite solution group only at 2 h. Therefore, the direct nasal brain transport efficiency of PAMAM dendrimer nanocomposites can be significantly improved after combining with in situ gel. PAMAM dendrimer nanocomposite/DGG is a potential drug delivery system for nasal brain transport.

An Available Strategy for Nasal Brain Transport of Nanocomposite Based on PAMAM Dendrimers via In Situ Gel