Comparative anti-inflammatory activity of poly(amidoamine) (PAMAM) dendrimer-dexamethasone conjugates with dexamethasone-liposomes

Lipophilicity vs hydrophicility physicochemical traits are extremely important variables that are active considerations for optimizing drug delivery systems. The comparative anti-inflammatory delivery potential of dexamethasone (dex) in an encapsulation-based (liposome-lipophilic) and poly (amidoamine) (PAMAM) dendrimer prodrug conjugation-based delivery systems (hydrophilic) was performed in this work. Dendrimer prodrug conjugates were characterized by H-1 NMR. The drug encapsulation efficiency for drug in liposomes was observed to be 14.02% and this was correlated with a dose-dependent tumor necrosis factor (TNF)-alpha inhibition (39-57% inhibition). The biological evaluation of nanocarriers for drug was demonstrated in a standard, conventionally used in vitro cell-based system for TNF-alpha inhibition. This served as a comparative tool to demonstrate a quantitatively higher TNF-alpha inhibition (67-71.48%) produced by the dendrimer-dex drug conjugate. The structure activity relationship (dose-for-dose) was inferred by relatively lesser inhibition of TNF-alpha by variants of PAMAM G4 (NH2) dendrimer-dex conjugates and was compared with liposomes carrying dex. In vitro results suggest that the prodrug conjugates of PAMAM dendrimer deliver dex to be more efficient in comparison with liposome-based dex in terms of higher TNF-alpha inhibition. This study has implications in designing efficient prodrug nanocarrier systems for delivering dex. (C) 2013 Elsevier B.V. All rights reserved.