Host−Guest Chemistry and Physicochemical Properties of the Dendrimer−Mycophenolic Acid Complex

Abstract

The nature of the dendrimer-mycophenolic acid (MPA) complex was investigated by (1)H NMR and 2D NOESY spectroscopy. The (1)H NMR analysis proved that the water-soluble supramolecular structure of the complex was formed based on ionic interactions between dendrimers and MPA molecules on the surface as well as hydrophobic interactions/hydrogen-bond interactions in the interior pockets of dendrimers. The 2D NOESY analysis predicted the localization of MPA molecules in the pockets of dendrimers and gave information on the detailed interactions between dendrimer scaffolds and MPA molecules in the interior. Further solubility and release studies investigated the physicochemical properties of the dendrimer-MPA complexes. These results showed that the host-guest chemistry of dendrimer-MPA complexes proposed by NMR techniques explains the solubilization and release behavior of MPA in the presence of PAMAM dendrimers well. The general host-guest chemistry of the dendrimer-drug complex is promising for the development of new drug delivery systems.

Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

“…The binding strength between dendrimer-guest complexes has been determined by isothermal titration calorimetry(ITC) [26][27][28][29], high performance liquid chromatography (HPLC) [30] and fluorescence spectroscopy [31][32][33]. Detailed conformations of dendrimers interacting with guest molecules have been studied by nuclear magnetic resonance(NMR) [34][35][36] and the size of the dendrimer-guest complexes has been measured by dynamic light scattering (DLS) [22,31]. For instance, supramolecular assemblies of polyamidoamine (PAMAM) dendrimers and phenanthrene, an organic pollutant, have been studied using fluorescence resonance energy transfer (FRET) to understand the interaction between dendrimers and guest molecules in aqueous solution [24].…”

Immunosuppressive and Anti-Inflammatory Properties of Engineered Nanomaterials

“…Cyclosporine Liposomes (Freise et al, 1994;Shah et al, 2006); polymeric NP (Gref et al, 2001;Italia et al, 2007;Azzi et al, 2010;Tang et al, 2012); lipid NP (Muller et al, 2008) Preclinical Tacrolimus Lipid NP (Pople and Singh, 2012); polymeric NP (Tammam et al, 2012); liposomes (Erdogan et al, 2002;Zhang et al, 2010) Preclinical Rapamycin/sirolimus Polymeric NP (Yuan et al, 2008;Woo et al, 2012;Shah et al, 2013); micelles (Yanez et al, 2008;Chen et al, 2013); liposomes (Rouf et al, 2009;Ghanbarzadeh et al, 2013) Preclinical Mycophenolic acid Polymeric NP (Shirali et al, 2011); nanogels (Look et al, 2013); dendrimers (Hu et al, 2009) Preclinical Corticosteroids Liposomes Linker et al, 2008;Schweingruber et al, 2011;Ulmansky et al, 2012); polymeric NP (Ishihara et al, 2005;Matsuo et al, 2009); solid lipid NP (Jensen et al, 2010;Zhang and Smith, 2011); dendrimers (Khandare et al, 2005) Preclinical Non-steroidal anti-inflammatory Dendrimers (Chauhan et al, 2004;Na et al, 2006;Chandrasekar et al, 2007;Cheng et al, 2007); nanocolloid (Milkova et al, 2013); lipid NP (Castelli et al, 2005); liposomes (Paavola et al, 2000;Srinath et al, 2000;Turker et al, 2008)…”

Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity

“…For pocket volume, it is known that the length of branching units for constructing PPI dendrimer is much shorter than that for PAMAM dendrimer (4-bond versus 7-bond), thereby the size of generation 4 PPI is much smaller than that of generation 3 PAMAM Further, the amido groups in the scaffold of PAMAM (60 amido groups in each generation 3 PAMAM) may facilitate the encapsulation of phenylbutazone molecules via hydrogen bond interactions (N-H in the amido group as hydrogen bond donor and oxygen atoms in phenylbutazone as receptors). 21 However, the effects of pocket volume and amido groups should be ruled out because more phenylbutazone molecules were found in the cavities of PPI dendrimer, which is evident by NOESY analysis and will be further discussed in the next sections. Finally, with regard to surface charge density, PPI with a smaller molecular size had a higher surface charge density than PAMAM (19.3 × 10 −3 /Å 2 versus 11.3 × 10 −3 /Å 2 ).…”

“…20 In comparison with interior encapsulation, surface ionic interaction was found to be the major factor on the solubilization behavior of PAMAM dendrimer. 3,13 The host behaviors of PAMAM dendrimer towards a list of drugs were analyzed by 1 H nuclear magnetic resonance (NMR) titrations, 21 nuclear Overhauser effect spectroscopy (NOESY), 3 and pulsed-field gradient NMR. 22 The release of drugs from the PAMAM dendritic matrix depends on dendrimer generation and surface functionality, ionic strength, pH conditions, and the solvent.…”

“…22 The release of drugs from the PAMAM dendritic matrix depends on dendrimer generation and surface functionality, ionic strength, pH conditions, and the solvent. 21 PAMAM dendrimer exhibits low biocompatibility in A549 and MCF-7 cell lines, and the removal of surface charges on PAMAM dendrimer by acetylation can completely neutralize the cytotoxic activity of dendrimer on these cells. 23 All these studies suggest that the surface amine groups on PAMAM dendrimers are of central importance in the binding, release, and biocompatibility of this polymeric nanocarrier.…”