title: Determination of binding constants of vasoactive intestinal peptide to poly(amidoamine) dendrimers designed for drug delivery using ACE.
abstract: The purpose of the present paper was to study at physiological pH the affinity between vasoactive intestinal peptide (VIP) and four poly(amidoamine) dendrimers (PAMAMs) designed for drug delivery. Therefore, a fast and reproducible CE method was first developed to analyze the strongly basic peptide. To allow an accurate determination of binding constant (K) values, the ability to suppress peptide adsorption onto the silica capillary of nonpermanent coatings (poly(ethylene oxide) (PEO), low and medium relative molecular masses poly(diallyldimethylammonium chloride) (PDDA)) or poly(acrylamide) permanent coating (PAA) was evaluated. Very good intraday repeatability of VIP migration times and peak areas (0.1-0.6 and 2.9-4.9% RSD, respectively) was obtained using two of the investigated coatings (PEO and PDDA with medium molecular mass). ACE combined with these dynamic coatings was then employed to evaluate K between VIP and two amine-terminated PAMAM dendrimers of generation 2 and 5 (G2.NH2, G5.NH2) and two carboxyl-terminated PAMAM derivatives of generation 2 and 5 (G2.COOH, G5.COOH). Binding constant of (6.7 +/- 1.1) x 10(4)/M could be determined for the couple VIP/G5.NH2, while no affinity was evidenced between VIP and all other dendrimers investigated. These results suggest that G5.NH2 might be an interesting carrier for the delivery of VIP.
authors.affiliation: University of Paris-Sud, Group of Proteins and Nanotechnologies in Separation Sciences, Châtenay-Malabry, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Dribek
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Potier
authors.forename: Arnaud
authors.initials: A
authors.lastname: Rodrigues
authors.forename: Antoine
authors.initials: A
authors.lastname: Pallandre
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
authors.forename: Myriam
authors.initials: M
authors.lastname: Taverna
mesh_terms: D050091:Dendrimers; D016503:Drug Delivery Systems; D019075:Electrophoresis, Capillary / Q000295:instrumentation / Q000379:methods*; D011073:Polyamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D014660:Vasoactive Intestinal Peptide; D011092:Polyethylene Glycols