Cyclodextrin-Modified Nanomaterials for Drug Delivery: Classification and Advances in Controlled Release and Bioavailability

Abstract

In drug delivery, one widely used way of overcoming the biopharmaceutical problems present in several active pharmaceutical ingredients, such as poor aqueous solubility, early instability, and low bioavailability, is the formation of inclusion compounds with cyclodextrins (CD). In recent years, the use of CD derivatives in combination with nanomaterials has shown to be a promising strategy for formulating new, optimized systems. The goals of this review are to give in-depth knowledge and critical appraisal of the main CD-modified or CD-based nanomaterials for drug delivery, such as lipid-based nanocarriers, natural and synthetic polymeric nanocarriers, nanosponges, graphene derivatives, mesoporous silica nanoparticles, plasmonic and magnetic nanoparticles, quantum dots and other miscellaneous systems such as nanovalves, metal-organic frameworks, Janus nanoparticles, and nanofibers. Special attention is given to nanosystems that achieve controlled drug release and increase their bioavailability during in vivo studies.

pH-Responsive Polymer Nanomaterials for Tumor Therapy

“…Researchers have designed pH-responsive polymer nanomaterials (10–100 nm) ( 33 ) that can be engineered to suit the need of the therapy and target area. These materials are relatively stable in the blood and normal tissue but are unstable in the tumor area (acidic pH), leading to rapid changes in the degree of ionization in pH-responsive groups, causing material changes that release the anti-tumor drugs, achieving the goal of targeted tumor therapy ( 34 , 35 ). Researchers have performed sustainable research on these pH-responsive polymer nanomaterials ( 36 , 37 ).…”

Advances in Nanostructures for Antimicrobial Therapy

“…Several colloidal delivery systems such as micro- and nanoemulsions [ 52 ], liposomes [ 53 , 54 , 55 ], solid lipid nanoparticles (SLNPs) [ 56 , 57 ], nanostructured lipid carriers (NLCs) [ 58 , 59 , 60 ], liquid crystalline NPs [ 61 ], biopolymer microgels [ 62 ], nanocapsules [ 63 ], cyclodextrins (CDs) [ 64 , 65 , 66 , 67 ], smart responsive materials polymer-based NPs [ 68 , 69 , 70 , 71 ] or dendrimers [ 72 , 73 ] can be used for encapsulation of pharmacologically active compounds. By internalization of drugs to nanocarriers (NCs) their stability, bioavailability, cellular uptake/internalization, and pharmacokinetic profile can be ameliorated along with the reduction of their toxicity [ 42 , 74 , 75 , 76 ].…”

“…These inorganic carriers are usually functionalized with the above-mentioned organic polymers, resulting in hybrid NCs, in which active molecules are trapped. Depending on the used material, different NCs are formed, such as liposomes/lipid-based delivery systems, polymeric NPs (micelles, spheres, capsules), dendrimers, polymeric complex NPs, CDs, nanocrystals, electrospun nanofibers, electro-sprayed NPs, nano-spray dried particles, covalent organic frameworks, hydrogels, inorganic nanosystems (quantum dots, carbon based NPs) [ 41 , 45 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 117 , 118 , 119 , 120 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 143 ]. Table 1 provides an overview of the types of nanoformulations discussed and their basic building blocks, while Figure 2 , Figure 3 , Figure 4 and Figure 5 illustrate the individual anti-infective drugs listed in this review.…”

“…Cyclodextrin (CD) [ 64 , 65 , 66 , 67 ] inclusion complexes, CD coupling, supramolecular hydrogels, and supramolecular micelles are the most frequently used CD-based controlled release systems [ 176 ]. By hydrophobic inclusion of oleylamine in β-CD, a supramolecular amphiphile was prepared, forming a self-assembled nanovesicles showing a size of 125.1 ± 8.30 nm and zeta potential of 19.3 ± 9.20 mV exhibiting sustained release of encapsulated VAN during 48 h and showing 2- and 4-fold lower minimum inhibitory concentrations (MICs) against S. aureus and MRSA as well as 459-fold reduction of intracellular bacteria using infected human embryotic kidney cells (HEK), and an 8-fold reduction in infected macrophages compared to bare drug [ 177 ].…”

Cyclodextrin-Based Nanosponges: Overview and Opportunities

“…Cyclodextrins show high reactivity as a consequence of their hydroxyl groups able to suffer substitution or elimination. Due to these properties, cyclodextrins can be directly copolymerized with other monomers or grafted onto organic or inorganic materials ( Mocanu et al, 2001 ; Cova T. F. et al, 2018 , 2021 ; Gómez-Graña et al, 2021 ; Real et al, 2021 ) allowing a significant increase in the range of applications for CDs. Due to the high content in hydroxyl groups, cyclodextrins can easily form reticulated structures by co-polymerization with appropriate crosslinkers.…”