title: Oleodendrimers: a novel class of multicephalous heterolipids as chemical penetration enhancers for transdermal drug delivery.
abstract: This paper reports synthesis and evaluation of Janus type generation G-1 and G-2 dendrimers. The dendrimers have been constructed by linking two building blocks, dendrons and oleic acid, through ester and amide bonds and were well characterized by Fourier-transform infrared (FT-IR), (1)H NMR, (13)C NMR and electrospray ionization mass spectrometry (ESI-MS). The dendrimers have been evaluated for in vitro cytotoxicity using sulforhodamine B assay (SRB assay) and in vivo skin irritation potential. The ester linked dendrimers did not exhibit any cytotoxicity even up to 80 μg/ml while G-1 and G-2 generations dendrimers with amide linkage exhibited toxicity above 70 μg/ml and 21 μg/ml, respectively, none of the dendrimers showed any skin irritation. All the dendrimers, tested for their skin permeation enhancement potential using diclofenac sodium (DS) as a model drug at a concentration of 1% in gels, showed significant increase in steady-state flux (ERflux) of the drug as compared to control (without enhancer), and oleic acid. Amongst the dendrimers, the ester linked G-1 and G-2 dendrimers showed highest ERflux, 3.33 ± 0.31 and 3.39 ± 0.21, respectively.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Kalhapure
authors.forename: Krishnacharya G
authors.initials: KG
authors.lastname: Akamanchi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D004008:Diclofenac / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D005782:Gels; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D019301:Oleic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D010539:Permeability; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D023422:Skin Irritancy Tests; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D050091:Dendrimers; D005782:Gels; D004008:Diclofenac; D019301:Oleic Acid
keywords: Anti-inflammatory; Dendrimers; Diclofenac sodium; Oleic acid; Oleodenrimers; Penetration enhancers; Transdermal delivery