Chemical conjugation with cyclodextrins as a versatile tool for drug delivery

Chu, Hui Min; Zhang, Rui Xia; Huang, Qing; Bai, Changcai; Wang, Zhizhong

doi:10.1007/s10847-017-0743-3

Cited by 14 publications

(10 citation statements)

References 87 publications

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“…This argument is supported by X-ray crystallography studies, which first elucidated the structure of the CD molecule [66][67][68], and which enabled researchers to discover the truncated cone shape [2]. The X-ray crystallography technique, however, is limited to solid state samples; therefore, it alone does not suffice to solidify the claim that CDs are rigid molecules, and it alone cannot explain why CDs form stable complexes with many types of molecules [9,19,59,[69][70][71][72][73][74][75][76]. Therefore, other analytical techniques are required to substantiate the conclusion that CDs are rigid molecules.…”

Section: Cyclodextrin Size Properties and Overall Flexibilitymentioning

confidence: 99%

Cyclodextrins: Structural, Chemical, and Physical Properties, and Applications

et al. 2021

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Due to their unique structural, physical and chemical properties, cyclodextrins and their derivatives have been of great interest to scientists and researchers in both academia and industry for over a century. Many of the industrial applications of cyclodextrins have arisen from their ability to encapsulate, either partially or fully, other molecules, especially organic compounds. Cyclodextrins are non-toxic oligopolymers of glucose that help to increase the solubility of organic compounds with poor aqueous solubility, can mask odors from foul-smelling compounds, and have been widely studied in the area of drug delivery. In this review, we explore the structural and chemical properties of cyclodextrins that give rise to this encapsulation (i.e., the formation of inclusion complexes) ability. This review is unique from others written on this subject because it provides powerful insights into factors that affect cyclodextrin encapsulation. It also examines these insights in great detail. Later, we provide an overview of some industrial applications of cyclodextrins, while emphasizing the role of encapsulation in these applications. We strongly believe that cyclodextrins will continue to garner interest from scientists for many years to come, and that novel applications of cyclodextrins have yet to be discovered.

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Section: Cyclodextrin Size Properties and Overall Flexibilitymentioning

confidence: 99%

Cyclodextrins: Structural, Chemical, and Physical Properties, and Applications

et al. 2021

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“…The peptide/protein conjugation belongs to one of the most popular groups owing to the ability to modulate their properties. Furthermore, the addition of CDs to the complexed structure of protein can involve many new abilities which are induced mostly by inclusion complex with other low or high-molecular weight particles [ 14 ]. In spite of many techniques to conjugate [ 19 ], there are still new modifications and strategies being developed in order to obtain CD-peptide/protein conjugates.…”

Section: Introductionmentioning

confidence: 99%

“…The peptide/protein conjugation belongs to one of the most popular groups owing to the ability to modulate their properties. Furthermore, the addition of CDs to the complexed structure Nowadays, the main core of attaching CDs to the biomolecules is focused on a conjugation method based on covalent-linking [14]. There are a significant amount of different molecules conjugated to the CDs, including peptides/proteins, nucleotides/nucleic acids [15], carbohydrates [16], steroids [17], and low molecular weight drugs [18].…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrins-Peptides/Proteins Conjugates: Synthesis, Properties and Applications

2021

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Cyclodextrins (CDs) are a family of macrocyclic oligosaccharides mostly composed of six, seven, or eight α-D-glucopyranose units with α-1,4-glycosidic bonds to form toroidal structures. The CDs possess a hydrophilic exterior and hydrophobic interior with the ability to form an inclusion complex, especially with hydrophobic molecules. However, most existing studies are about conjugation CDs with peptide/protein focusing on the formation of new systems. The CD-peptide/protein can possess new abilities; particularly, the cavity can be applied in modulation properties of more complexed proteins. Most studies are focused on drug delivery, such as targeted delivery in cell-penetrating peptides or co-delivery. The co-delivery is based mostly on polylysine systems; on the other hand, the CD-peptide allows us to understand biomolecular mechanisms such as fibryllation or stem cell behaviour. Moreover, the CD-proteins are more complexed systems with a focus on targeted therapy; these conjugates might be controllable with various properties due to changes in their stability. Finally, the studies of CD-peptide/protein are promising in biomedical application and provide new possibilities for the conjugation of simple molecules to biomolecules.

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“…A formação desses complexos ocorre de maneira simples e reversível, o que possibilita diferentes arranjos supramoleculares. Ciclodextrinas, ciclofanos e valinomicina são alguns exemplos de moléculas cíclicas utilizadas para formação de complexos de inclusão(CHU et al, 2017;GANGEMI et al, 2018). homogêneas e não higroscópicas.…”

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“…Tridimensionalmente, as CDs apresentam-se em forma cônica, em função da conformação cadeira das unidades de glicopiranose, e a disposição dos grupamentos hidroxila (-OH) na estrutura das CDs levam à formação de uma superfície externa hidrofílica e uma cavidade interna lipofílica que justificam sua considerável solubilidade em meio aquoso. Os grupos hidroxila ligados ao carbono 2 e ao carbono 3 da molécula de glicose são denominados grupos primários e estão localizados na parte mais larga da estrutura cônica das CDs, enquanto que o grupo hidroxila ligado ao carbono 6 encontra-se na região mais estreita da estrutura(CHU et al, 2017; FRÖMMING e SZEJTLI, 1993; SANTOS e COELHO, 2009).As CD, portanto, são tipicamente moléculas "hospedeiras", nas quais é possível incluir uma variedade de moléculas, em diferentes proporções (Figura 8), com tamanho compatível com sua cavidade interior, que varia em função do número de unidades de glicopiranose, conforme é possível observar nos dados da Tabela 1(CHU et al, 2017). O mecanismo de formação do complexo varia conforme a molécula a ser encapsulada, mas, no geral, é regido por processos entálpicos na liberação de moléculas de água do interior da cavidade, bem como por interações eletrostáticas, ligações de hidrogênio, interações hidrofóbicas, mudanças conformacionais e interações de transferências de carga(SURVANA et al, 2017).Entre três as CD naturais citadas anteriormente, apesar de a -CD apresentar a menor solubilidade em água, é a CD com a melhor capacidade de formar complexos com diferentes fármacos hidrofóbicos, possui síntese mais facilitada em relação às demais, estando disponível em maiores quantidades com menor custo, além de possuir uso aprovado como excipiente para preparações farmacêuticas (LAZA-KNOERR; GREF e COUVREUR, 2010).O uso de CDs combinado com FSs é estudado desde a década de 1990 e mostra uma promissora estratégia para entrega facilitada de FSs hidrofóbicos.…”

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Inclusão supramolecular de Hipericina em β-ciclodextrina visando aplicação em terapia fotodinâmica

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Photodynamic Therapy (PDT) is a technique based on the interaction of a nontoxic and light-sensitive dye, called photosensitizer (PS), with light at an appropriate wavelength that in the presence of oxygen results in the formation of reactive species that causes cell death. Some PSs, e.g. hypericin (HY), are hydrophobic and causes aggregation in water media, affecting the PDT application. Obtaining of cyclodextrins (CD) inclusion complexes can improve some properties of PSs such as solubility and bioavailability. This study aimed to produce an inclusion complex between HY and β-Cyclodextrin (β-CD) to improve HY solubility and to study the effect of this improvement on its chemical, photochemical and biological properties for application in PDT. The inclusion complex β-CDHY formation was confirmed by FTIR and NMR-1 H spectroscopy techniques. HY solubility was improved and its photochemical properties (chemical stability, photostability, photodynamic activity, and quantum yield) were not affected after being included in the β-CD cavities. The complex β-CDHY presented an in vitro release six times faster than HY free. Besides, β-CDHY exhibited a slower cutaneous permeation profile, indicating the possibility of being applied in topic uses due to the greater retention in superficial skin layers. Intracellular accumulation of free and complexed HY, as well as the cito and phototoxicity, were evaluated in HeLa, MCF7 e Vero cell lines. In HeLa cells there was nearby two times fold improvement in accumulation, leading to an increase of 40% in the phototoxicity of β-CDHY related to free HY in 3, 6 and 10 J cm -2 . In MCF7 cells, the intracellular accumulation was the same for free and complexed HY, however, there was a decrease of about 20% in IC50 values when the complex was incubated within the cells under 3 and 6 J cm -2 . In Vero cells it was obtained a cell uptake 10 3 times lower than the values for HeLa and MCF7, suggesting that free and complexed HY accumulate selectively in carcinogenic cells.Therefore, these results suggest that the use of β-CD as a drug delivery system for HY is effective and allows its application in Photodynamic Therapy. O 2 -Oxigênio singlete AF -Atividade fotodinâmica ALAácido 5-aminolevulênico AUácido úrico β-CD -Beta-ciclodextrina β-CDHY -Complexo de inclusão entre β-CD e HY CAQI -Central de Análises Químicas Instrumentais CD -Ciclodextrina CIS -Cruzamento intersistema DLS -Dynamic Light Scattering DMEM -Dulbecco's Modified Medium DMSO -Dimetilsulfóxido DP -Desvio Padrão DPBF -1,3-Difenilisobenzofurano ECestrato córneo ERO -Espécies Reativas de Oxigênio FS -Fotossensibilizador GPX-4 -Glutationa peroxidase HY -Hipericina HP-β-CD -Hidroxipropil-β-Ciclodextrina IV -Espectroscopia na região do Infravermelho Jfluxo de permeação LD -Limite de detecção LED -Light-emitting Diode LQ -Limite de quantificação

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Chemical conjugation with cyclodextrins as a versatile tool for drug delivery

Cited by 14 publications

References 87 publications

Cyclodextrins: Structural, Chemical, and Physical Properties, and Applications

Cyclodextrins: Structural, Chemical, and Physical Properties, and Applications

Cyclodextrins-Peptides/Proteins Conjugates: Synthesis, Properties and Applications

Inclusão supramolecular de Hipericina em β-ciclodextrina visando aplicação em terapia fotodinâmica

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Chemical conjugation with cyclodextrins as a versatile tool for drug delivery

Cited by 14 publications

References 87 publications

Cyclodextrins: Structural, Chemical, and Physical Properties, and Applications

Cyclodextrins: Structural, Chemical, and Physical Properties, and Applications

Cyclodextrins-Peptides/Proteins Conjugates: Synthesis, Properties and Applications

Inclusão supramolecular de Hipericina em &beta;-ciclodextrina visando aplicação em terapia fotodinâmica

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Inclusão supramolecular de Hipericina em β-ciclodextrina visando aplicação em terapia fotodinâmica