Solubilization and Release Properties of Dendrimers. Evaluation as Prospective Drug Delivery Systems

Abstract

The polarity and accessibility to the interior of several dendrimers using phenanthrene, anthracene and tetrabenzonaphtalene as probe molecules have been investigated. In addition the prospective application of the dendrimers as drug carriers was evaluated by incorporating 5(6)-methylbenzo[1,2-c]1,2,5-oxadiazole N 1 -oxide] (1) and 2 0 -(benzo[1,2-c] 1,2,5-oxadiazol-5(6)-yl(N 1 -oxide) methylidene]-1-methoxy methane hydrazide (2). These compounds have antichagasic therapeutic activity but very low water solubility, which limits their application. Polypropylene imine dendrimers with amine terminal groups (DAB-16AT and DAB-32AT) and polyamide amine (PAMAM) dendrimers with carboxylate terminal groups (PAMAM-32CT), with amine terminal groups, (PAMAM-8AT and PAMAM-32AT) and with hydroxyl terminal groups (PAMAM-32OHT) were chosen for this study. Approximately one molecule of phenanthrene or anthracene was encapsulated in PAMAM-32CT, PAMAM-32AT, PAMAM-32OHT and DAB-32AT dendrimers. However, slight encapsulation was observed working with PAMAM-8AT and DAB-16AT. The studies with tetrabenzonaphtalene show that the guest molecule might only be partially caged within the dendrimer host. However, for relatively insoluble solutes the efficiency to encapsulate can be dictated by the saturation in the aqueous phase besides the dendrimer capacity to dissolve it. These dendrimers are also able to encapsulate and consequently solubilize 1 and 2 oxadiazol. However, PAMAM dendrimers are better for encapsulation and retention due to guest-host specific interactions. These interactions can be diminished by lowering the pH to allow a controlled deliverance of the drug.

Dendrimers for Enhanced Drug Solubilization

“…In this group, model compounds have been utilized to study the encapsulation behavior of dendrimers with regard to specific aspects, such as effect of length of PEG surface chains, influence of acid and salt addition to the bulk solution, use of poly(phosphazene) moieties as surface shell, and evaluation of the encapsulation efficiency using aromatic compounds as probe molecules (Figure 10) [46][47][48][49][50]. Although these studies are in early stages and do not involve existing API, they provide further insight into the dendrimer delivery platform and will be discussed briefly.…”

Anionic PAMAM dendrimers as drug delivery vehicles for transition metal-based anticancer drugs

“…Dendrimers are uniform, spherical polymers capable of accommodating guest molecules on their surface or within large interior cavities [13][14][15][16][17][18]. PAMAM dendrimers ( Fig.…”

Association of a Weakly Acidic Anti-Inflammatory Drug (Ibuprofen) with a Poly(Amidoamine) Dendrimer as Studied by Molecular Dynamics Simulations

“…These attributes enable PAMAM dendrimers to enhance drug solubilization and to facilitate the transport and the controlled release of complexed pharmaceutical and biological molecules at targeted sites. 8,14,15 Among other biomedical uses, PAMAM dendrimers have recently emerged as promising candidates for the encapsulation and the delivery of poorly water-soluble drugs belonging to class II compounds in the Biopharmaceutical Classification System 16 (i.e., characterized by poor solubility but high permeability), which still pose a challenge in drug formulation. [17][18][19] Although significant advances have been made through experimental observations regarding the association of such drug moieties with PAMAM dendrimers 15, [20][21][22] and several mechanisms have been proposed to explain the observed behavior, 14,21,23 a molecular-level description that can offer both qualitative and quantitative information is particularly desirable if optimized formulations for such drugs are to be pursued.…”