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PLGA Nanoparticles Loaded Cerebrolysin: Studies on Their Preparation and Investigation of the Effect of Storage and Serum Stability with Reference to Traumatic Brain Injury
Univ Modena & Reggio Emilia, Dept Life Sci, Lab Pharmaceut Technol, I-41125 Modena, Italy..
Univ Modena & Reggio Emilia, Dept Life Sci, Lab Pharmaceut Technol, I-41125 Modena, Italy..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
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2015 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, no 2, 899-912 p.Article in journal (Refereed) Published
Abstract [en]

Cerebrolysin is a peptide mixture able to ameliorate symptomatology and delay progression of neurological disorders such as Alzheimer's disease and dementia. The administration of this drug in humans presents several criticisms due to its short half-life, poor stability, and high doses needed to achieve the effect. This paper investigates the potential of polylactic-co-glycolide (PLGA) nanoparticles (NPs) as sustained release systems for iv administration of cerebrolysin in normal and brain injured rats. NPs were prepared by water-in-oil-in-water (w/o/w) double emulsion technique and characterized by light scattering for mean size and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The NPs produced by double sonication under cooling at 60 W for 45 s, 12 mL of 1 % w:v of PVA, and 1:0.6 w:w drug/PLGA ratio (C-NPs4) displayed an adequate loading of drug (24 +/- 1 mg/100 mg of NPs), zeta potential value (-13 mV), and average diameters (ranged from 250 to 330 nm) suitable to iv administration. SEM images suggested that cerebrolysin was molecularly dispersed into matricial systems and partially adhered to the NP surface. A biphasic release with an initial burst effect followed by sustained release over 24 h was observed. Long-term stability both at room and at low temperature of freeze-dried NPs was investigated. To gain deeper insight into NP stability after in vivo administration, the stability of the best NP formulation was also tested in serum. These PLGA NPs loaded with cerebrolysin were able to reduce brain pathology following traumatic brain injury. However, the size, the polydispersivity, and the surface properties of sample were significantly affected by the incubation time and the serum concentration.

Place, publisher, year, edition, pages
2015. Vol. 52, no 2, 899-912 p.
Keyword [en]
Nanoparticles (NPs), Polylactic-co-glycolide (PLGA), Cerebrolysin, Long-termstability, Serumstability, Traumatic brain injury, Neuroprotection
National Category
Anesthesiology and Intensive Care Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-263422DOI: 10.1007/s12035-015-9235-xISI: 000360687200009PubMedID: 26108180OAI: oai:DiVA.org:uu-263422DiVA: diva2:860635
Funder
Swedish Research Council, 2710-HSSSwedish Foundation for Strategic Research AstraZenecaGöran Gustafsson Foundation for Research in Natural Sciences and Medicine
Available from: 2015-10-13 Created: 2015-09-30 Last updated: 2017-12-01Bibliographically approved

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Sharma, Hari ShankerSharma, Aruna

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