Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules

Higashi, Taishi; Iohara, Daisuke; Motoyama, Keiichi; Arima, Hisatomi

doi:10.1248/cpb.c17-00765

Cited by 41 publications

(21 citation statements)

References 173 publications

(175 reference statements)

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“…This would, anyway, represent a conceptual approximation of the actual subject matter [53,54], as such an approach would fail to consider any of the supramolecular phenomena, synergisms and antagonisms, that occur in the context of a mixture of compounds. Importantly, these phenomena are nowadays known to potentially alter the pharmacodynamic and kinetic profiles of the individual components in a mixture, thus generating profiles that are different to those that are observed when the same compounds are studied as isolated [55,56]. It becomes apparent that ad hoc designed experimental setups are needed in order to determine the peculiarities of mixtures [57].…”

Section: Discussionmentioning

confidence: 99%

Researching New Therapeutic Approaches for Abdominal Visceral Pain Treatment: Preclinical Effects of an Assembled System of Molecules of Vegetal Origin

Parisio,

Lucarini,

Micheli

et al. 2019

Nutrients

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Abdominal pain is a frequent symptom of irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBDs). Although the knowledge of these pathologies is progressing, new therapeutic strategies continue to be investigated. In the present study, the effect of a system of molecules of natural origin (a medical device according to EU Directive 93/42/EC, engineered starting from Boswellia serrata resins, Aloe vera polysaccharides and Matricaria chamomilla and Melissa officinalis polyphenols) was evaluated against the intestinal damage and visceral pain development in DNBS-induced colitis model in rats. The system (250 and 500 mg kg−1) was orally administered once daily, starting three days before the injection of 2,4-dinitrobenzenesulfonic acid (DNBS) and for 14 days thereafter. The viscero-motor response (VMR) to colon-rectal balloon distension (CRD) was used as measure of visceral sensitivity. The product significantly reduced the VMR of DNBS-treated animals. Its effect on pain threshold was better than dexamethasone and mesalazine, and not lower than amitriptyline and otilonium bromide. At microscopic and macroscopic level, the tested system was more effective in protecting the intestinal mucosa than dexamethasone and mesalazine, promoting the healing of tissue lesions. Therefore, we suggest that the described system of molecules of natural origin may represent a therapeutic option to manage painful bowel diseases.

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Section: Discussionmentioning

confidence: 99%

Researching New Therapeutic Approaches for Abdominal Visceral Pain Treatment: Preclinical Effects of an Assembled System of Molecules of Vegetal Origin

Parisio,

Lucarini,

Micheli

et al. 2019

Nutrients

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“…Nonviral gene delivery suffers from a number of limitations, including short transgene expression times and low transfection efficiency. Supramolecular chemistry is an extremely useful and important domain for understanding pharmaceutical sciences because various physiological reactions and drug activities are based on supramolecular chemistry; especially, CD-based supramolecules are promising systems in the DDS field [ 91 ]. Motoyama et al reported whether PPRXs of PEG (Mw 2,000)-grafted α-CD (α-CD)/PAMAM dendrimer conjugate (PEG-α-CDE (G2, DSC1.5, DSP4) with CDs have the potential for the novel sustained release systems for pDNA.…”

Section: Supramolecular With Peg-appended Cde As Sustained Release System Of Pdnamentioning

confidence: 99%

Twenty Years of Research on Cyclodextrin Conjugates with PAMAM Dendrimers

Arima

2021

Pharmaceutics

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Recently, the number of gene and oligonucleotide drugs are increasing. Of various drug delivery systems (DDSs) for gene and oligonucleotide drugs, few examples of the clinical application of polymer as drug carriers are known, despite development of the novel polymers has been progressing. Cyclodextrin (CD) conjugates with starburst polyamidoamine (PAMAM) dendrimer (CDEs), as a new type of polymer-based carriers, were first published in 2001. After that, galactose-, lactose-, mannose-, fucose-, folate-, and polyethyleneglycol (PEG)-appended CDEs have been prepared for passive and active targeting for gene, oligonucleotide, and low-molecular-weight drugs. PEG-appended CDE formed polypsuedorotaxanes with α-CD and γ-CD, which are useful for a sustained release system of gene and oligonucleotide drugs. Interestingly, CDEs were found to have anti-inflammatory effects and anti-amyloid effects themselves, which have potential as active pharmaceutical ingredients. Most recently, CDE is reported to be a useful Cas9-RNA ribonucleoproteins (Cas9 RNP) carrier that induces genome editing in the neuron and brain. In this review, the history and progression of CDEs are overviewed.

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“…In this context, cyclodextrin (CD) and CD derivatives have been explored as drug delivery agents since several decades based on their favorable solubilizing capabilities for hydrophobic drugs, their high absorption capacity and their low toxicity. In fact, plain supramolecular CD assemblies were applied as active pharmaceutical ingredients (APIs) against a number of diseases, e.g., by affecting the cholesterol homeostasis in leukemic cells [ 2 , 3 ]. Mostly, however, they are used as carriers to improve the bioavailability of many APIs by forming noncovalent inclusion complexes that are being explored in a number of clinical trials [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin Encapsulated in Crosslinked Cyclodextrin Nanoparticles Enables Immediate Inhibition of Cell Growth and Efficient Killing of Cancer Cells

2021

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The efficiency of anti-cancer drugs is commonly determined by endpoint assays after extended incubation times, often after days. Here we demonstrate that curcumin encapsulated in crosslinked cyclodextrin nanoparticles (CD-NP) acts extremely rapidly on cell metabolism resulting in an immediate and complete inhibition of cell growth and in efficient cancer-cell killing only few hours after incubation. This early onset of anti-cancer action was discovered by live-cell high-throughput fluorescence microscopy using an environmental stage. To date, only very few examples of covalently crosslinked nanoscale CD-based (CD-NP) drug carriers exist. Crosslinking cyclodextrins enables the adsorption of unusually high payloads of hydrophobic curcumin (762 µg CC/mg CD-NP) reflecting a molar ratio of 2.3:1 curcumin to cyclodextrin. We have investigated the effect of CD-NP encapsulated curcumin (CD-CC-NP) in comparison to free, DMSO-derived curcumin nanoparticles (CC-NP) on 4 different cell lines. Very short incubations times as low as 1 h were applied and cell responses after medium change were subsequently followed over two days. We show that cell proliferation is inhibited nearly immediately in all cell lines and that a cell- and concentration dependent cancer-cell killing occurs. Anti-cancer effects were similar with free and encapsulated curcumin, however, encapsulation in CD-NP drastically extends the long-term photostability and anti-cancer activity of curcumin. Curcumin-sensitivity is highest in HeLa cells reaching up to 90% cell death under these conditions. Sensitivity decreased from HeLa to T24 to MDA MB-231 cells. Strikingly, the immortalized non-cancerous cell line MCF-10A was robust against curcumin concentrations that were highly toxic to the other cell lines. Our results underline the potential of curcumin as gentle and yet effective natural anti-cancer agent when delivered solvent-free in stabilizing and biocompatible drug carriers such as CD-NP that enable efficient cellular delivery.

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Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules

Cited by 41 publications

References 173 publications

Researching New Therapeutic Approaches for Abdominal Visceral Pain Treatment: Preclinical Effects of an Assembled System of Molecules of Vegetal Origin

Researching New Therapeutic Approaches for Abdominal Visceral Pain Treatment: Preclinical Effects of an Assembled System of Molecules of Vegetal Origin

Twenty Years of Research on Cyclodextrin Conjugates with PAMAM Dendrimers

Curcumin Encapsulated in Crosslinked Cyclodextrin Nanoparticles Enables Immediate Inhibition of Cell Growth and Efficient Killing of Cancer Cells

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