Development of Nutraceutical Emulsions as Risperidone Delivery Systems: Characterization and Toxicological Studies

Igartúa, Daniela E.; Calienni, Maria; Feas, Daniela Agustina; Chiaramoni, Nadia Silvia; Prieto, María Jimena

doi:10.1002/jps.24636

Cited by 21 publications

(16 citation statements)

References 46 publications

(76 reference statements)

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“…In vitro release of CBZ from D-CBZ complexes was studied against buffer solutions at different pH (2.2, 7.4 and 12.6) by using a micro-dialysis Eppendorf tube diffusion technique in which the top internal flap-cover of a 0.5 mL Eppendorf tube is replaced with a dialysis membrane (MW cut-off: 12000 from Sigma-Aldrich-Merck, Argentina). This technique was developed ad hoc to overcome micro-quantities of the released drug (Igartúa et al, 2015). D-CBZ complexes or free drug were sealed into the micro-dialysis Eppendorf tube and incubated in the different buffers under continuous stirring.…”

Section: In Vitro Drug Release Studiesmentioning

confidence: 99%

“…Adult zebrafish (Danio rerio) were maintained at 28.0 ± 1.0 °C in aquaria with a 14 h light − 10 h dark cycle, as described previously Igartúa et al, 2015). Fishes were fed with dry flakes (TetraMin PRO®) three times a day and nauplius larvae of Artemia once a day.…”

Section: Animalsmentioning

confidence: 99%

“…The spontaneous movement was studied in a multichannel ADC system (WMicrotracker, Designplus SRL, Argentina) as previously described in Igartúa et al (2015) (Igartúa et al, 2015). Activity events were recorded for 15 min at 1, 4, 24 and 48 hpi, at room temperature.…”

Section: Neurotoxicitymentioning

confidence: 99%

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PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Igartúa

Martínez

Temprana

et al. 2018

International Journal of Pharmaceutics

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Carbamazepine (CBZ) is an antiepileptic drug, which also could be used in the treatment of neurodegenerative diseases, such as the Alzheimer's disease. However, its use has been limited due to its low solubility, inefficient pharmacokinetic profiles, and multiple side effects. PAMAM dendrimers, ethylenediamine core, generation 4.0 (amine terminal groups) and 4.5 (carboxylate terminal groups) (DG4.0 and DG4.5 respectively) are polymers that can increase drug solubility through complexation. Thus, the aim of this work was to obtain and characterize complexes between CBZ and dendrimers. Both DG4.0 and DG4.5 allowed the incorporation of ∼20 molecules of CBZ per dendrimer, into their hydrophobic pockets. DG4.0-CBZ and DG4.5-CBZ complexes were found to be stable for 90 days at 37 °C and resistant to a lyophilization process, presenting controlled drug release. Also, the complexes nanotoxicity was tested ex vivo (human red blood cells), in vitro (N2a cell line), and in vivo (zebrafish). No hemolytic effect was observed in the ex vivo model. As regards in vitro toxicity, the DG4.5-CBZ complexes significantly reduced the toxicity caused by the free drug. Moreover, the DG4.5-CBZ did not cause neurotoxicity or cardiotoxicity in zebrafish larvae. In conclusion, a stable and biocompatible drug delivery system based on the DG4.5 capable of complex the CBZ has been developed. This achievement highlights the advantages of using negatively charged dendrimers for nanomedicine.

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Section: In Vitro Drug Release Studiesmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

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PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Igartúa

Martínez

Temprana

et al. 2018

International Journal of Pharmaceutics

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“…Swimming activity was recorded during 15 minutes at 4, 5, 6, and 7 dpf, after inoculation with the formulation tested, at room temperature with a multichannel ADC system (WMicrotracker, Designplus SRL, Argentina) that detects the refraction of infrared beams through the zebrafish bodies. 23 Variations over 3% of the signal received (an empirical threshold previously determined) were considered as activity events. Swimming activity was calculated summing up the number of activity events for 15 minutes.…”

Section: Measurement Of Locomotor Activitymentioning

confidence: 99%

Skin penetration and UV‐damage prevention by nanoberries

Bucci

Prieto

Milla

et al. 2017

J of Cosmetic Dermatology

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“…Over the last few years, zebrafish (Danio rerio) has frequently been employed for biosafety evaluation of nanoparticles and several anticancer nanoformulations (Igartúa et al, 2015;. This biosafety evaluation should include both the study of the toxicity (non-specific and undesired effects of a drug or nanoparticle) and the biocompatibility (ability to be in contact with a living system without producing an adverse effect) of drugs and nanoparticles (Vert et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Folic acid magnetic nanotheranostics for delivering doxorubicin: Toxicological and biocompatibility studies on Zebrafish embryo and larvae

Igartúa

Azcona

Martínez

et al. 2018

Toxicology and Applied Pharmacology

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Doxorubicin (DOXO) is a chemotherapeutic agent widely used for the treatment of solid tumors and hematologic malignancies in both adults and children. However, DOXO causes short- and long-term cardiotoxicity and others undesirable side effects, such as nephrotoxicity and neurotoxicity. Magnetic nanoparticles (MNPs) allow the delivery of drugs specifically to target place, employing an external magnet. Moreover, they may act as contrast agents in MRI providing information on the diagnostic of diverse pathologies. In this way, two functions may be combined in a unique nanosystem known as theranostic. Also, the MNPs can be modified with folic acid (MNPs@FA) to increase the uptake by cancer cells that overexpress the FA receptors. In previous works, our collaborators obtained and characterized MNPs, MNPs@FA, and MNPs@FA@DOXO. It is essential to study the biosafety of nanotheranostic, and there is no published study of FeO nanoparticles developmental toxicity. Because of that, this work aimed to study the in vivo toxicity and biocompatibility of DOXO, MNPs@FA, and MNPs@FA@DOXO using zebrafish embryo and larvae as an animal model. Viability, developmental toxicity, changes in spontaneous movement (neurotoxicity), changes in cardiac rhythm (cardiotoxicity), and efficiency of DOXO-uptake were studied. While the 48-h treatment with 50 μg/mL of DOXO resulted in a 30% larvae death and the development of significant morphological abnormalities, the treatment with MNPs@FA@DOXO and MNPs@FA did not reduce the viability and did not cause developmental abnormalities. Besides, the MNPs@FA@DOXO reduced the cardiotoxicity and promoted a more rapid and significant uptake of DOXO by zebrafish larvae.

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Development of Nutraceutical Emulsions as Risperidone Delivery Systems: Characterization and Toxicological Studies

Cited by 21 publications

References 46 publications

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Skin penetration and UV‐damage prevention by nanoberries

Folic acid magnetic nanotheranostics for delivering doxorubicin: Toxicological and biocompatibility studies on Zebrafish embryo and larvae

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