Determination of binding constants of vasoactive intestinal peptide to poly(amidoamine) dendrimers designed for drug delivery using ACE

被引:11
|
作者
Dribek, Mohamed
Le Potier, Isabelle
Rodrigues, Arnaud
Pallandre, Antoine
Fattal, Elias
Taverna, Myriam
机构
[1] Univ Paris Sud, Grp Prot & Nanotechnol Separat Sci, Chatenay Malabry, France
[2] Univ Paris Sud, Grp Drug Targeting & Delivery Poorly Stable Drugs, Chatenay Malabry, France
[3] CNRS, Chatenay Malabry, France
关键词
ACE; drug delivery; peptide adsorption; poly(amidoamine) dendrimers; vasoactive intestinal peptide;
D O I
10.1002/elps.200600768
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2191 / 2200
页数:10
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