A novel retinoic/butyric hyaluronan ester for the treatment of acute promyelocytic leukemia: preliminary preclinical results

Coradini, Danila; Pellizzaro, Cinzia; Scarlata, Ignazio; Zorzet, Sonia; Garrovo, Chiara; Abolafio, Gabriella; Speranza, Annalisa; Fedeli, Maya; Cantoni, Silvia; Sava, Gianni; Daidone, Maria Grazia; Perbellini, A

doi:10.1038/sj.leu.2404179

Cited by 16 publications

(12 citation statements)

References 17 publications

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“…Conversely, sodium butyrate or retinoic acid alone or in association, at the conjugate equivalent doses, did not improve animal survival. Similar results were obtained in the case of DBA/2 mice intraperitoneally inoculated with RetA-resistant P388 cells [94].…”

Section: All-trans Retinoic Acidsupporting

confidence: 86%

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Polysaccharide-Based Anticancer Prodrugs

Caliceti

Salmaso

Bersani

2009

Macromolecular Anticancer Therapeutics

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So far, polysaccharides have been widely used in pharmaceutical technology as first choice excipients for production of traditional formulations. Nevertheless, in the recent years these natural and semisynthetic macromolecules have been addressed for new challenging applications as functional materials for innovative formulations. Their peculiar physicochemical and biological properties have been exploited to develop macromolecular prodrugs which can exhibit favorable biopharmaceutical properties and enforce the therapeutic performance of the parent drugs. These polymers display, in fact, high biocompatibility and biodegradability, multiple insertion points, and biological properties that can be advantageously exploited in drug delivery. In particular, the multifunctional structures of these polymers are anchoring points for conjugation of several anticancer drugs, which usually suffer from poor physicochemical, biopharmaceutical, and therapeutic properties that limit their therapeutic performance and proper use in anticancer treatment. Polysaccharide-based anticancer prodrugs can be designed to endow derivatives with new bioresponse, targeting, or environmental triggering properties or to combine molecules with synergistic therapeutic effect. Over the years, a variety of synthetic protocols have been set up to conjugate anticancer drugs to the polysaccharide backbone via specific linkages or through spacers which convey to the conjugates selective drug-delivery properties. Furthermore, the intrinsic antitumor activity and cell-targeting properties of few polysaccharides represent an additional value to the final therapeutic systems. Anticancer drugs with different pharmacodynamic, pharmacokinetic, and physicochemical properties have been successfully conjugated to various natural and semisynthetic polysaccharides highlighting the interesting perspectives for exploitation of new promising anticancer polymer therapeutics.

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Section: All-trans Retinoic Acidsupporting

confidence: 86%

“…The conjugate was obtained by derivatization of HA tetrabutylammonium salt with retinoyl chloride in organic solvent followed by the polymer reaction with butyric anhydride [94].…”

Section: All-trans Retinoic Acidmentioning

confidence: 99%

Polysaccharide-Based Anticancer Prodrugs

Caliceti

Salmaso

Bersani

2009

Macromolecular Anticancer Therapeutics

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“…Previous evidence has indicated that histone deacetylase (HDAC) inhibitors (HDACi), including sodium butyrate (NaBu), trichostatin A, and valproic acid, have produced beneficial effects in preclinical models of renal and cardiovascular diseases (4,26). Both in vitro and in vivo studies have also indicated synergism between ATRA and HDACi when they are used to treat renal cell carcinomas (8,55). It has been suggested that hyaluronan mixed ester of butyric and retinoic acid enhances cardiac repair in infarcted rat and pig hearts (58,66).…”

mentioning

confidence: 99%

Inhibition of HDAC enhances STAT acetylation, blocks NF-κB, and suppresses the renal inflammation and fibrosis in Npr1 haplotype male mice

Kumar

Gogulamudi

Periasamy

et al. 2017

American Journal of Physiology-Renal Physiology

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Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) plays a critical role in the regulation of blood pressure and fluid volume homeostasis. Mice lacking functional (coding for GC-A/NPRA) exhibit hypertension and congestive heart failure. However, the underlying mechanisms remain largely less clear. The objective of the present study was to determine the physiological efficacy and impact of all--retinoic acid (ATRA) and sodium butyrate (NaBu) in ameliorating the renal fibrosis, inflammation, and hypertension in gene-disrupted haplotype (1-copy; +/-) mice (50% expression levels of NPRA). Both ATRA and NaBu, either alone or in combination, decreased the elevated levels of renal proinflammatory and profibrotic cytokines and lowered blood pressure in mice compared with untreated controls. The treatment with ATRA-NaBu facilitated the dissociation of histone deacetylase (HDAC) 1 and 2 from signal transducer and activator of transcription 1 (STAT1) and enhanced its acetylation in the kidneys of mice. The acetylated STAT1 formed a complex with nuclear factor-κB (NF-κB) p65, thereby inhibiting its DNA-binding activity and downstream proinflammatory and profibrotic signaling cascades. The present results demonstrate that the treatment of the haplotype mice with ATRA-NaBu significantly lowered blood pressure and reduced the renal inflammation and fibrosis involving the interactive roles of HDAC, NF-κB (p65), and STAT1. The current findings will help in developing the molecular therapeutic targets and new treatment strategies for hypertension and renal dysfunction in humans.

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“…In the case of P388 cells, which also highly express CD44 receptors [26], the inhibition concentration was found to be slightly but significantly higher than cisplatin. The same was found for the complex, whose activity was instead slightly but significantly higher than that of cisplatin and loaded nanoparticles in A2780 and A549 cells.…”

Section: Antiproliferative and Apoptotic Activitymentioning

confidence: 96%

Preparation, characterisation and preliminary antitumour activity evaluation of a novel nanoparticulate system based on a cisplatin-hyaluronate complex and N-trimethyl chitosan

Cafaggi¹,

Russo²,

Stefani³

et al. 2009

Invest New Drugs

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In this work, nanoparticles with a positive surface charge were prepared through the electrostatic interaction of a new cisplatin-hyaluronate complex with N-trimethyl chitosan (substitution degree of 85%). Mean particle diameter was approximately 195 nm. Drug loading of nanoparticles, which had a zeta potential of about 27 mV, was equal to 6% w/w. After 24 h, while the cisplatin-hyaluronate complex released approximately 60% w/w drug in phosphate buffered saline at pH 7.4, approximately 40% w/w of total cisplatin was released from nanoparticles. The same cumulative amounts of released drug were found after 48 h. These nanoparticles, as well as the starting cisplatin-hyaluronate complex, were active on all cell lines tested (P388, A2780, A549), with an antiproliferative activity similar to that of cisplatin. Apoptosis was markedly induced in A2780 cells by nanoparticles. In a preliminary in vivo experiment, the antitumour activity against a murine tumour (P388 cells) subcutaneously implanted in mice, resulted similar to that of cisplatin for nanoparticles whereas the starting complex showed a non-significant activity at the cisplatin dose tested. Body weight change of treated mice suggested a significantly better tolerance of the nanoparticles compared to cisplatin, after an initial brief period of acute toxicity higher than the parent drug. These results indicate that such a particulate system could be useful as a carrier for cisplatin delivery.

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A novel retinoic/butyric hyaluronan ester for the treatment of acute promyelocytic leukemia: preliminary preclinical results

Cited by 16 publications

References 17 publications

Polysaccharide-Based Anticancer Prodrugs

Polysaccharide-Based Anticancer Prodrugs

Inhibition of HDAC enhances STAT acetylation, blocks NF-κB, and suppresses the renal inflammation and fibrosis in Npr1 haplotype male mice

Preparation, characterisation and preliminary antitumour activity evaluation of a novel nanoparticulate system based on a cisplatin-hyaluronate complex and N-trimethyl chitosan

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