Intravenous administration of retinoic acid-loaded polymeric nanoparticles prevents ischemic injury in the immature brain

Machado-Pereira, Marta; Santos, Tiago; Ferreira, Lino; Bernardino, Liliana

doi:10.1016/j.neulet.2018.02.066

Cited by 16 publications

(10 citation statements)

References 31 publications

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“…RA/RAR signaling is critical for BBB differentiation and integrity 90 from ischemic stroke patients 24 . Moreover, when intravenously injected, RA formulations restored neuronal and vascular functions in a prenatal model of brain ischemia 91 .…”

Section: Ra Delivery Systems For Brain Diseasesmentioning

confidence: 95%

“…The formulation enhanced endothelial cell proliferation and tubule network formation and protected against ischemia-induced death in endothelial cell lines and endothelial progenitor cells isolated from ischemic stroke patients 24 . Moreover, when intravenously injected, RA formulations restored neuronal and vascular functions in a prenatal model of brain ischemia 91 .…”

Section: Ra Delivery Systems For Brain Diseasesmentioning

confidence: 95%

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Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine

et al. 2020

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Retinoids regulate a wide spectrum of cellular functions from the embryo throughout adulthood, including cell differentiation, metabolic regulation, and inflammation. These traits make retinoids very attractive molecules for medical purposes. In light of some of the physicochemical limitations of retinoids, the development of drug delivery systems offers several advantages for clinical translation of retinoid-based therapies, including improved solubilization, prolonged circulation, reduced toxicity, sustained release, and improved efficacy. In this Review, we discuss advances in preclinical and clinical tests regarding retinoid formulations, specifically the ones based in natural retinoids, evaluated in the context of regenerative medicine, brain, cancer, skin, and immune diseases. Advantages and limitations of retinoid formulations, as well as prospects to push the field forward, will be presented. R etinoic acid (RA) signaling is one of the most important biological pathways in nature, triggered by RA interaction with nuclear receptors that control gene expression. The chemical structure of retinol (vitamin A, a RA precursor) was first described by Paul Karrer in 1931 1 , who was awarded a Nobel Prize in 1937 for the discovery. The use of RA for skin disorders 2 and cancer treatment (acute myeloid leukemia (AML) 3 and cervical neoplasia 4,5) started in the 1960s and 1980s (Fig. 1). By the 2000s, RA had been incorporated in many tissue engineering scaffolds as a stem cell differentiation agent 6,7. Over the last 10 years, many discoveries related to the biological role of RA in controlling the biology of hematopoietic stem cells 8,9 , tumor-initiating cells 10-12 , immune cells 13 , intestinal mucosa wound repair 14 , cancer resistance 15 , and cell reprogramming and differentiation 16,17 , have further stimulated the interest in this drug for many other biomedical applications. This interest is confirmed by more than 50 active clinical trials (according to ClinicalTrials.gov) evaluating the effect of RA in cancer (28 trials), mostly in hematological (16 trials) and brain tumors (8 trials), skin pathologies (e.g., acne, photoaging, eczema) (5 trials), and in other conditions such as inflammation, olfactory loss, and neuropsychiatric diseases (Table 1). Clinical applications of RA have highlighted three main limitations of its pharmacological use. First, RA is poorly soluble in aqueous solutions 18 and photosensitive 19 , which makes its administration challenging. Secondly, RA induces irritation when applied onto the skin and increases its catabolism, when it is administered intravenously, reducing its therapeutic efficacy 20. Lastly, RA is involved in many biological processes and thus the systemic delivery of RA causes side effects. All these limitations motivated researchers to synthesize novel and

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Section: Ra Delivery Systems For Brain Diseasesmentioning

confidence: 95%

Section: Ra Delivery Systems For Brain Diseasesmentioning

confidence: 95%

Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine

et al. 2020

Self Cite

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“…Indeed, the use of RA-loaded polymeric nanoparticles (RA-NPs) modulates the murine microglial response towards an anti-inflammatory and neuroprotective phenotype (M2-like) in organotypic hippocampal slice cultures [ 143 ]. Recently, the intravenous administration of RA-NPs was shown to prevent ischemic injury in the immature brains of 2-day-old mice, demonstrating the role of RA in the control of neuroinflammation [ 144 ].…”

Section: Immunomodulatory Effect Of Ra During Inflammatory Processmentioning

confidence: 99%

Impact of Retinoic Acid on Immune Cells and Inflammatory Diseases

Oliveira

Teixeira

Sato

2018

Mediators of Inflammation

172

128

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Vitamin A metabolite retinoic acid (RA) plays important roles in cell growth, differentiation, organogenesis, and reproduction and a key role in mucosal immune responses. RA promotes dendritic cells to express CD103 and to produce RA, enhances the differentiation of Foxp3+ inducible regulatory T cells, and induces gut-homing specificity in T cells. Although vitamin A is crucial for maintaining homeostasis at the intestinal barrier and equilibrating immunity and tolerance, including gut dysbiosis, retinoids perform a wide variety of functions in many settings, such as the central nervous system, skin aging, allergic airway diseases, cancer prevention and therapy, and metabolic diseases. The mechanism of RA is interesting to explore as both a mucosal adjuvant and a combination therapy with other effective agents. Here, we review the effect of RA on innate and adaptive immunity with a special emphasis on inflammatory status.

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“…Although nanoparticle-mediated drug delivery has been extensively evaluated in adult experimental stroke models [260][261][262][263][264][265][266][267][268][269], there are no studies in animal models of perinatal stroke. Nevertheless, recently a study has been published where the effects of retinoic acid-loaded polymeric NPs in the prevention of ischemic injury in the immature brain were evaluated in vitro [270]. Retinoic acid-loaded polymeric NPs were found to inhibit cell death and normalize markers of neurovascular function and inflammation in hippocampal organotypic slice cultures exposed to oxygen and glucose deprivation.…”

Section: Nanoparticles Evaluated In Perinatal Strokementioning

confidence: 99%

Advanced nanotherapies to promote neuroregeneration in the injured newborn brain

Arteaga

Mikrogeorgiou

Kannan

et al. 2019

Advanced Drug Delivery Reviews

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Neonatal brain injury affects thousands of babies each year and may lead to long-term and permanent physical and neurological problems. Currently, therapeutic hypothermia is standard clinical care for term newborns with moderate to severe neonatal encephalopathy. Nevertheless, it is not completely protective, and additional strategies to restore and promote regeneration are urgently needed. One way to ensure recovery following injury to the immature brain is to augment endogenous regenerative pathways. However, novel strategies such as stem cell therapy, gene therapies and nanotechnology have not been adequately explored in this unique age group. In this perspective review, we describe current efforts that promote neuroprotection and potential targets that are unique to the developing brain, which can be leveraged to facilitate neuroregeneration.

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Intravenous administration of retinoic acid-loaded polymeric nanoparticles prevents ischemic injury in the immature brain

Cited by 16 publications

References 31 publications

Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine

Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine

Impact of Retinoic Acid on Immune Cells and Inflammatory Diseases

Advanced nanotherapies to promote neuroregeneration in the injured newborn brain

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