Recent Advances in the Pharmaceutical and Biomedical Applications of Cyclodextrin-Capped Gold Nanoparticles

Abstract

The real problem in pharmaceutical preparation is drugs' poor aqueous solubility, low permeability through biological membranes, and short biological t_1/2. Conventional drug delivery systems are not able to overcome these problems. However, cyclodextrins (CDs) and their derivatives can solve these challenges. This article aims to summarize and review the history, properties, and different applications of cyclodextrins, especially the ability of inclusion complex formation. It also refers to the effects of cyclodextrin on drug solubility, bioavailability, and stability. Moreover, it focuses on preparing and applying gold nanoparticles (AuNPs) as novel drug delivery systems. It also studies the uses and effects of cyclodextrins in this field as novel drug carriers and targeting devices. The system formulated from AuNPs linked with CD molecules combines the advantages of both CD and AuNPs. Cyclodextrins benefit in increasing aqueous drug solubility, loading capacity, stability, and size control of gold NPs. Also, AuNPs are applied as diagnostic and therapeutic agents because of their unique chemical properties. Plus, AuNPs possess several advantages such as ease of detection, targeted and selective drug delivery, greater surface area, high loading efficiency, and higher stability than microparticles. In the present article, we tried to present the potential pharmaceutical applications of CD-derived AuNPs in biomedical applications including antibacterial, anticancer, gene-drug delivery, and various targeted drug delivery applications. Also, the article highlighted the role of CDs in the preparation and improvement of catalytic enzymes, the formation of self-assembling molecular print boards, the fabrication of supramolecular functionalized electrodes, and biosensors formation.

Keywords: AuNPs; cancer management; drug delivery; drug targeting; inclusion complexes; nanotechnology.

Figure 1

Schematic representation of α-, β-, and γ-Cyclodextrin, and the chemical derivatization of β-CD molecule.

Figure 2

Phase solubility diagram of β-CD. According to Higuchi and Connors, the types of phase-solubility diagrams of cyclodextrin presenting the solubility behavior of the included drugs upon increasing the CD concentration are two types (A and B) curves. Type (A) phase diagram is classified into three subtypes; AL: linear diagram; AP: positive deviation from linearity; AN: negative deviation from linearity. Also, type (B) is classified into two subtypes; B S: indicating the complex of limited solubility; and B I: showing the insoluble complex.

Figure 3

Schematic representation of the common CD complexation methods.

Figure 4

Schematic representation of the common methods for AuNPs synthesis.

Figure 5

Schematic representation of CD-AuNPs applications.

Figure 6

Formation of the ternary system which is composed of the inclusion complexation of guest drug (eg, anticancer drug) in the β-CD cavity and then conjugation with gold nanoparticles (β-CD-S(CH₂)6-S-AuNPs) for drug delivery.

Figure 7

The representation of the aggregation and the competitive dissociation of smart AuNPs-β-CD via the addition of either guest molecules (ie, PEG-Ad or diazo) causing aggregation, or α-CD as compotator host molecules.

Figure 8

Schematic representation of CD-AuNPs immobilization on Ad substrate via inclusion complexation for pDNA concentration according to the following steps. (1) Ad-modified self-assembled monolayer (SAM) gold substrate; (2) Immobilization of PEI-pDNA polyplex NPs on the modified SAM; (3) pDNA using Heparane; (4) Immobilization of β-CD-PEI-pDNA polyplex NPs on the modified SAM; (5) pDNA using Heparane.

Figure 9

Chemical structures of adamantly functionalized PPI dendrimers (Ad-PPI) and their formation of inclusion complexes with cyclodextrins to construct water-soluble assemblies (A); the formation of a monolayer of these modified assemblies on a gold substrate via adsorption (CD-AuNPs monolayer) (B); and formation of multilayer CD-assemblies on gold (C). Reproduced with permission from Copyright 2002 Wiley VCH GmbH.

Figure 10

Schematic representation of the multicomponent nanostructures construction using (A) CD-Au and Fc-SiO; (B) The nano-assembly from small NPs to large NPs; and (C) nano-assembly from large NPs to small NPs. The artwork was reproduced from MDPI according to permission via license: CC BY 4.0.

Figure 11

Schematic illustration of Fullerene tube or cylindrical structure (A), ball-like structure (B), and the formation of water-soluble nanoaggregates via the inclusion complexation between Fullerene and γ-CD-decorating AuNPs (C).