Improvement of Drug Properties by Cyclodextrins

Uekama, Kaneto; Hirayama, Fumitoshi

doi:10.1016/b978-0-12-374194-3.00040-8

Cited by 9 publications

(5 citation statements)

References 154 publications

(149 reference statements)

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“…Furthermore, no significant difference was found between the solubility of lamotrigine from the physical mixture and the inclusion complex. The enhancement in aqueous solubility of lamotrigine can be explained in terms of wetting property and hydrophilicity of bCD, with simultaneous reduction in the crystallinity of the drug caused by the kneading process and inclusion into the hydrophobic cavity of the bCD (Szetli 1994;Uekama & Hirayama 1996;Trapani et al 2000). All solid dispersion systems displayed higher solubility of lamotrigine than pure drug.…”

Section: Saturation Solubility Studiesmentioning

confidence: 99%

Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion technique

Shinde¹,

Shelake

Shetty³

et al. 2008

Journal of Pharmacy and Pharmacology

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The solid-state properties and dissolution behaviour of lamotrigine in its inclusion complex with beta-cyclodextrin (betaCD) and solid dispersions with polyvinylpyrrolidone K30 (PVP K30) and polyethyleneglycol 6000 were investigated. The phase solubility profile of lamotrigine with betaCD was classified as AL-type, indicating formation of a 1:1 stoichiometry inclusion complex, with a stability constant of 369.96+/-2.26 M(-1). Solvent evaporation and kneading methods were used to prepare solid dispersions and inclusion complexes, respectively. The interaction of lamotrigine with these hydrophilic carriers was evaluated by powder X-ray diffractometry, Fourier transform infrared spectroscopy and differential scanning calorimetry. These studies revealed that the drug was no longer present in crystalline state but was converted to an amorphous form. Among the binary systems tested, PVP K30 (1:5) showed greatest enhancement of the solubility and dissolution of lamotrigine.

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Section: Saturation Solubility Studiesmentioning

confidence: 99%

Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion technique

Shinde¹,

Shelake

Shetty³

et al. 2008

Journal of Pharmacy and Pharmacology

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“…Because of its high anticancer activity, hampered A suitable stability and solubility in water are essential properties for a drug or drug candidate, as they are closely related to bioavailability. Many anti-cancer drugs suffer from low aqueous solubilities and this problem prevents their oral administration [19]. This challenge can be met by the formulation of these drugs in nano-delivery watersoluble systems [20,21].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation

et al. 2021

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The use of cyclodextrins as drug nano-carrier systems for drug delivery is gaining importance in the pharmaceutical industry due to the interesting pharmacokinetic properties of the resulting inclusion complexes. In the present work, complexes of the anti-cancer alkaloids camptothecin and luotonin A have been prepared with β-cyclodextrin and hydroxypropyl-β-cyclodextrin. These cyclodextrin complexes were characterized by nuclear magnetic resonance spectroscopy (NMR). The variations in the 1H-NMR and 13C-NMR chemical shifts allowed to establish the inclusion modes of the compounds into the cyclodextrin cavities, which were supported by docking and molecular dynamics studies. The efficiency of the complexation was quantified by UV-Vis spectrophotometry and spectrofluorimetry, which showed that the protonation equilibria of camptothecin and luotonin A were drastically hampered upon formation of the inclusion complexes. The stabilization of camptothecin towards hydrolysis inside the cyclodextrin cavity was verified by the quantitation of the active lactone form by reverse phase liquid chromatography fluorimetric detection, both in basic conditions and in the presence of serum albumin. The antitumor activity of luotonin A and camptothecin complexes were studied in several cancer cell lines (breast, lung, hepatic carcinoma, ovarian carcinoma and human neuroblastoma) and an enhanced activity was found compared to the free alkaloids, particularly in the case of hydroxypropyl-β-cyclodextrin derivatives. This result shows that the cyclodextrin inclusion strategy has much potential towards reaching the goal of employing luotonin A or its analogues as stable analogues of camptothecin.

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“…Therefore, an important step of manual curation is always necessary to establish a more consistent pathway reconstruction. In our work, this was the case for the detected reactions in the drug metabolism -other enzymes category, composed of enzymes participating in the fluorouracil pathway, for which analogs are widely used to treat breast and gastrointestinal carcinomas (Uekama and Hirayama, 2008). The anticancer effects of these drugs in mammals are exerted through the inhibition of thymidylate synthase and the misincorporation of its metabolites into RNA and DNA in place of uracil or thymine.…”

Section: Identification Of Overrepresented Pathwaysmentioning

confidence: 91%

“…In this pathway, the prodrugs capecitabine, tegafur, and carmofur, which are masked-form analogs of 5-fluorouracil (5-FU), are metabolized. These analogs are widely used to treat breast and gastrointestinal carcinomas (Uekama and Hirayama, 2008).…”

Section: The Xenobiotic Class Includes Overrepresented Enzymesmentioning

confidence: 99%

Definition of the Metagenomic Profile of Ocean Water Samples From the Gulf of Mexico Based on Comparison With Reference Samples From Sites Worldwide

et al. 2022

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Computational and statistical analysis of shotgun metagenomes can predict gene abundance and is helpful for elucidating the functional and taxonomic compositions of environmental samples. Gene products are compared against physicochemical conditions or perturbations to shed light on the functions performed by the microbial community of an environmental sample; however, this information is not always available. The present study proposes a method for inferring the metabolic potential of metagenome samples by constructing a reference based on determining the probability distribution of the counts of each enzyme annotated. To test the methodology, we used marine water samples distributed worldwide as references. Then, the references were utilized to compare the annotated enzymes of two different water samples extracted from the Gulf of Mexico (GoM) to distinguish those enzymes with atypical behavior. The enzymes whose annotation counts presented frequencies significantly different from those of the reference were used to perform metabolic reconstruction, which naturally identified pathways. We found that several of the enzymes were involved in the biodegradation of petroleum, which is consistent with the impact of human hydrocarbon extraction activity and its ubiquitous presence in the GoM. The examination of other reconstructed pathways revealed significant enzymes indicating the presence of microbial communities characterizing each ocean depth and ocean cycle, providing a fingerprint of each sampled site.

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Improvement of Drug Properties by Cyclodextrins

Cited by 9 publications

References 154 publications

Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion technique

Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion technique

Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation

Definition of the Metagenomic Profile of Ocean Water Samples From the Gulf of Mexico Based on Comparison With Reference Samples From Sites Worldwide

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