Characterization of Albendazole-Randomly Methylated-β-Cyclodextrin Inclusion Complex and In Vivo Evaluation of Its Antihelmitic Activity in a Murine Model of Trichinellosis

Garcı́a, Agustina; Leonardi, Darío; Vasconi, María D.; Hinrichsen, Lucila I.; Lamas, María Celina

doi:10.1371/journal.pone.0113296

Cited by 30 publications

(22 citation statements)

References 32 publications

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“…Despite their therapeutic efficacy, both ABZ and RBZ present poor aqueous solubility and limited absorption after oral administration. Pharmaceutical technology has developed several strategies to overcome solubility and absorption limitations of insoluble drugs such as solid dispersions [29], micellar formulations [30,31], nano-and microstructured systems [20,32,33], co-crystals [34], and cyclodextrin (CD) inclusion complexes [35][36][37][38][39].…”

Section: Introductionmentioning

confidence: 99%

Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer

Priotti

Baglioni²,

Garcı́a

et al. 2018

AAPS PharmSciTech

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This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com". Abstract.Drug repositioning refers to the identification of new therapeutic indications for drugs already approved. Albendazole and ricobendazole have been used as anti-parasitic drugs for many years; their therapeutic action is based on the inhibition of microtubule formation. Therefore, the study of their properties as antitumor compounds and the design of an appropriate formulation for cancer therapy is an interesting issue to investigate. The selected compounds are poorly soluble in water, and consequently, they have low and erratic bioavailability. In order to improve their biopharmaceutics properties, several formulations employing cyclodextrin inclusion complexes were developed. To carefully evaluate the in vitro and in vivo antitumor activity of these drugs and their complexes, several studies were performed on a breast cancer cell line (4T1) and BALB/c mice. In vitro studies showed that albendazole presented improved antitumor activity compared with ricobendazole. Furthermore, albendazole:citrate-β-cyclodextrin complex decreased significantly 4T1 cell growth both in in vitro and in vivo experiments. Thus, new formulations for anti-parasitic drugs could help to reposition them for new therapeutic indications, offering safer and more effective treatments by using a well-known drug.

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Section: Introductionmentioning

confidence: 99%

Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer

Priotti

Baglioni²,

Garcı́a

et al. 2018

AAPS PharmSciTech

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“…Though anthelmintics such as mebendazole and albendazole are commonly used to treat it but none of these drugs are fully effective against the encysted or newborn larvae of T. spiralis (García et al, 2014). In recent years, there has been a growing interest in developing newer anthelmintics for the treatment of trichinellosis that led to the testing of other drugs.…”

Section: Introductionmentioning

confidence: 99%

Carbonic anhydrase enzyme as a potential therapeutic target for experimental trichinellosis

et al. 2016

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Trichinellosis is a globally distributed helminthic infection. There is a considerable interest in developing new anti-helminthic drugs affecting all the developmental stages of Trichinella. Acetazolamide (carbonic anhydrase (CA) inhibitor) involves a novel mechanism of action by inhibiting such an essential enzyme for parasite metabolism. This work aimed to study the effect of acetazolamide against different stages of T. spiralis in experimental animals. Mice were divided into three groups: group I: infected and treated with acetazolamide on day 2 post infection (P.I.), group II: infected and treated with acetazolamide on day 12 P.I., and group III: infected non-treated. From each group, small intestine and muscles were removed for histopathological and immunohistochemical studies. Also, total adult and muscle larval count were estimated. We found that acetazolamide was effective in reduction of both adult and muscle larval counts. When given early, the effect was more pronounced on the adults (62.7 %). However, the efficacy of the drug against muscle larvae was increased when given late (63 %). Improvement of the intestinal histopathological changes was observed in all the treated groups. Degeneration of encysted larvae with minimal pathologic changes of infected skeletal muscle was observed in the treated groups. Expression of matrix metalloproteinase-9 showed a statistically significant decrease in the intestinal and muscle tissues in all treated groups as compared to the control group. In conclusion, the present study revealed that acetazolamide, carbonic anhydrase inhibitor, could be a promising drug against both adults and larvae of T. spiralis.

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“…Substitution of any of the hydrogen bonds forming hydroxyl groups results in notable improvement in its aqueous solubility [9,10]. CD derivatives of pharmaceutical interest include the hydroxypropyl derivatives of β and γ-CD, the randomly methylated-β-CD, sulfobutylether-β-CD, citrate-β-CD, succinyl-β-CD, and the branched CDs such as glucosyl-β-CD [7,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…Since CDs can form water-soluble inclusion complexes with many poorly soluble lipophilic drugs, they are used to enhance the drug aqueous solubility and to improve its bioavailability after oral administration [12,13]. The formation of complexes with CDs is one of the several strategies employed to increase solubility, dissolution rate and oral bioavailability of such poorly water-soluble drugs [9,11,14,15].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and characterization of a new cyclodextrin derivative with improved properties to design oral dosage forms

Garcı́a

Priotti

Codina

et al. 2018

Drug Deliv. and Transl. Res.

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This work aimed to synthesize a novel β-cyclodextrin derivative, itaconyl-β-cyclodextrin to evaluate whether albendazole inclusion complexes with the new β-cyclodextrin derivative-improved albendazole dissolution efficiency and its anthelminthic activity. The new derivative was thoroughly evaluated and characterized, and an average degree of substitution of 1.4 per cyclodextrin molecule was observed. Albendazole:itaconyl-β-cyclodextrin complexes were prepared by spray drying procedures and investigated using phase solubility diagrams, dissolution efficiency, X-ray diffraction, differential scanning calorimetry, Fourier transform infrared, scanning electronic microscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Phase solubility diagrams and mass spectrometry studies showed that the inclusion complex was formed in an equimolar ratio. Stability constant values were 602 M −1 in water, and 149 M −1 in HCl 0.1 N. Nuclear magnetic resonance experiments of the inclusion complex showed correlation signals between the aromatic and propyl protons of albendazole and the itaconyl-βcyclodextrin inner protons. The studies indicated solid structure changes of albendazole included in itaconyl-β-cyclodextrin. The maximum drug release was reached at 15 min, and the inclusion complex solubility was 88-fold higher than that of the pure drug. The in vitro anthelmintic activity assay showed that the complex was significantly more effective than pure albendazole.

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Characterization of Albendazole-Randomly Methylated-β-Cyclodextrin Inclusion Complex and In Vivo Evaluation of Its Antihelmitic Activity in a Murine Model of Trichinellosis

Cited by 30 publications

References 32 publications

Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer

Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer

Carbonic anhydrase enzyme as a potential therapeutic target for experimental trichinellosis

Synthesis and characterization of a new cyclodextrin derivative with improved properties to design oral dosage forms

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