The application of cyclodextrins in drug solubilization and stabilization of nanoparticles for drug delivery and biomedical applications

Abstract

Nanoparticles (NPs) have gained significant attention in recent years due to their potential applications in pharmaceutical formulations, drug delivery systems, and various biomedical fields. The versatility of colloidal NPs, including their ability to be tailored with various components and synthesis methods, enables drug delivery systems to achieve controlled release patterns, improved solubility, and increased bioavailability. The review discusses various types of NPs, such as nanocrystals, lipid-based NPs, and inorganic NPs (i.e., gold, silver, magnetic NPs), each offering unique advantages for drug delivery. Despite the promising potential of NPs, challenges such as physical instability and the need for surface stabilization remain. Strategies to overcome these challenges include the use of surfactants, polymers, and cyclodextrins (CDs). This review highlights the role of CDs in stabilizing colloidal NPs and enhancing drug solubility. The combination of CDs with NPs presents a synergistic approach that enhances drug delivery and broadens the range of biomedical applications. Additionally, the potential of CDs to enhance the stability and therapeutic efficacy of colloidal NPs, making them promising candidates for advanced drug delivery systems, is comprehensively reviewed.

Introduction

Over recent years, nanotechnology has emerged as of great interest in pharmaceutical formulations, drug delivery systems, and biomedical applications. Nanotechnology-based drug delivery systems play an essential role in reducing side effects and enhancing the therapeutic efficacy of various compounds and chemotherapy. Nanoparticles (NPs) are tiny particles ranging from 1 to 1000 nm in size, possessing numerous beneficial properties such as controlled drug release patterns, improved drug solubility, enhanced dissolution rates, and increased bioavailability (Ramadi et al., 2016). Their nano-scale dimensions, large surface area, and reactive surfaces contribute to unique physicochemical and biological properties (Khan et al., 2019). NPs can be tailored with different components and synthesis methods to achieve various structural and physicochemical properties, including morphology, size, surface functionalities, and electrical properties (Pathak et al., 2021).

The stable interaction between NPs and various ligands, their variable sizes and shapes, high loading capacities, and ease of functionalization with both hydrophobic and hydrophilic molecules make NPs desirable nanoplatforms for targeted and controlled delivery in disease treatment, diagnostics, and biomedical applications (Martinho et al., 2011). However, a drawback of developing these NPs for commercial use is their physical instability, which can lead to aggregate formation and affect their technological applications. Several reviews have discussed about the strategies to overcome these challenges using ligands, polymers, surfactants, proteins and amino acids, and cryoprotectants (Bakshi, 2016, Lee et al., 2009, Okada et al., 2018, Sultana et al., 2020).

Cyclodextrins (CDs) are cyclic oligosaccharides composed of sugar molecules with 1,4-α-D-glucopyranose linkages. CD possesses a hollow cone-shaped structure, with a hydrophobic interior and a hydrophilic exterior (Crini, 2014). They enhance the solubility of hydrophobic compounds, improve the permeation through biological barriers, and increase the stability of labile drugs through host–guest interactions (Loftsson and Brewster, 1996, Uekama and Otagiri, 1987). Combining CDs with NPs enables a wide range of promising applications. The synergistic use of CDs with NPs is beneficial for drug delivery and biomedical applications without altering the intrinsic properties of NPs or therapeutic compounds (Yang et al., 2014). The combination of complexing and plasmonic properties in CD-modified NPs expands their potential in biomedical applications, enabling simultaneous actions such as photodynamic and/or photothermal therapies, as well as chemotherapy (Cutrone et al., 2017). Additionally, the supramolecular complexes formed by CDs can maintain the therapeutic activity and stability of drugs, thereby increasing drug concentration at the site of action. This review highlights the role of CDs in enhancing drug solubility and stabilizing colloidal nanoparticulate systems for drug delivery and biomedical applications.

Physicochemical properties of CDs and their applications

Cyclodextrins (CDs) are cyclic oligosaccharides derived from starch degradation by glycotransferase enzymes. They are classified into three main types, that are α-cyclodextrin (αCD), β-cyclodextrin (βCD), and γ-cyclodextrin (γCD), containing 6, 7, and 8 glucopyranose units, respectively. CDs possess a unique chemical structure characterized by a truncated cone or torus shape, with a hydrophobic inner cavity and hydrophilic exterior (Loftsson and Duchêne, 2007). The hydroxyl (–OH) functional

Hay Man Saung Hnin Soe, Thorsteinn Loftsson, Phatsawee Jansook, The application of cyclodextrins in drug solubilization and stabilization of nanoparticles for drug delivery and biomedical applications, International Journal of Pharmaceutics, Volume 666, 2024, 124787, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124787.