title: Nanocapsules with Polyelectrolyte Shell as a Platform for 1,25-dihydroxyvitamin D3 Neuroprotection: Study in Organotypic Hippocampal Slices.
abstract: Calcitriol (1,25-dihydroxyvitamin D3), an active metabolite of vitamin D3, besides the role in calcium and phosphorus metabolism, plays a role in maintaining the functions of the brain. Active forms of vitamin D3 stimulate neurotrophic factors' expression, regulate brain immune processes, and prevent neuronal damage. Therefore, a potential utility of vitamin D3 in a therapy of neurodegenerative disorders should be taken into account. On the other hand, systemic vitamin D3 treatment carries the risk of undesirable effects, e.g., hypercalcemia. Thus, 1,25-dihydroxyvitamin D3 targeting delivery by nanoparticles would be a tremendous advancement in treatment of brain disorders. Calcitriol was enclosed in emulsion-templated nanocapsules with different polymeric shells: PLL (Poly(L-lysine hydrobromide)), PLL/PGA (/Poly(L-glutamic acid)), and PLL/PGA-g-PEG (Poly(L-glutamic acid) grafted with polyethylene glycol). The average size of all synthesized nanocapsules ranged from -80 to -100 nm. Biocompatibilities of synthesized nanocarriers were examined in hippocampal organotypic cultures in basal conditions and after treatment with lipopolysaccharide (LPS) using various biochemical tests. We demonstrated that nanocapsules coated with PLL were toxic, while PLL/PGA- and PLL/PGA-g-PEG-covered ones were nontoxic and used for further experiments. Our study demonstrated that in LPS-treated hippocampal slices, both types of loaded nanoparticles have protective ability. Our findings underlined that the neuroprotective action of vitamin D3 in both free and nanoparticle forms seems to be related to the suppression of LPS-induced nitric oxide release.
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343, Krakow, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ślusarczyk
authors.affiliation: Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, 8 Niezapominajek St, 30-239, Krakow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Piotrowski
authors.affiliation: Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, 8 Niezapominajek St, 30-239, Krakow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szczepanowicz
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Regulska
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343, Krakow, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Leśkiewicz
authors.affiliation: Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, 8 Niezapominajek St, 30-239, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Warszyński
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343, Krakow, Poland.
authors.forename: Bogusława
authors.initials: B
authors.lastname: Budziszewska
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343, Krakow, Poland.
authors.forename: Władysław
authors.initials: W
authors.lastname: Lasoń
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343, Krakow, Poland. basta@if-pan.krakow.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Basta-Kaim
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D018698:Glutamic Acid / Q000737:chemistry; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides; D053769:Nanocapsules / Q000737:chemistry / Q000633:toxicity; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism; D010316:Particle Size; D000071228:Polyelectrolytes / Q000737:chemistry; D011092:Polyethylene Glycols; D011107:Polylysine / Q000031:analogs & derivatives; D017207:Rats, Sprague-Dawley; D046509:Tissue Culture Techniques; D018675:Toxicity Tests
chemical_list: D008070:Lipopolysaccharides; D053769:Nanocapsules; D018696:Neuroprotective Agents; D000071228:Polyelectrolytes; C443714:polylysine-graft-(poly(ethylene glycol)); D011107:Polylysine; D009569:Nitric Oxide; D018698:Glutamic Acid; D011092:Polyethylene Glycols; D007770:L-Lactate Dehydrogenase; D002117:Calcitriol
keywords: 1,25-dihydroxyvitamin D3; Encapsulation; Hippocampal organotypic cultures; Nanocapsules; Neurodegeneration; Neuroprotection; Nitric oxide; Polyelectrolytes