title: Comparative anti-inflammatory activity of poly(amidoamine) (PAMAM) dendrimer-dexamethasone conjugates with dexamethasone-liposomes.
abstract: 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 (1)H 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.
authors.affiliation: School of Biosciences & Technology, VIT University, Vellore, Vellore Dt., 632014, India.
authors.forename: Arpankumar
authors.initials: A
authors.lastname: Choksi
authors.forename: K V L
authors.initials: KV
authors.lastname: Sarojini
authors.forename: Prashant
authors.initials: P
authors.lastname: Vadnal
authors.forename: Charmaine
authors.initials: C
authors.lastname: Dias
authors.forename: P K
authors.initials: PK
authors.lastname: Suresh
authors.forename: Jayant
authors.initials: J
authors.lastname: Khandare
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes; D011355:Prodrugs; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D050091:Dendrimers; D008081:Liposomes; C104700:PAMAM Starburst; D011355:Prodrugs; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone