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 1H 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)-α 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-α inhibition. This served as a comparative tool to demonstrate a quantitatively higher TNF-α 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-α 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-α inhibition. This study has implications in designing efficient prodrug nanocarrier systems for delivering dex.

Graphical abstractNanocarrier systems (a) liposome and (b) PAMAM dendrimers.Figure optionsDownload full-size imageDownload high-quality image (160 K)Download as PowerPoint slide