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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

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Abstract

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.

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Acknowledgments

This investigation is supported in part by grants from the Air Force Office of Scientific Research (EOARD, London, UK), and Air Force Material Command, USAF, under grant number FA8655-05-1-3065; Swedish Medical Research Council (Nr 2710-HSS), Swedish Strategic Research Foundation, Stockholm, Sweden; Göran Gustafsson Foundation, Stockholm, Sweden (HSS), Astra Zeneca, Mölndal, Sweden (HSS/AS), The University Grants Commission, New Delhi, India (HSS/AS), Ministry of Science and Technology, Govt. of India and Govt. of Sweden (HSS/AS), Indian Medical Research Council, New Delhi, India (HSS/AS); and India-EU Research Co-operation Program (AS/HSS).

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Technology, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, I-41125, Modena, Italy

    Barbara Ruozi, Daniela Belletti, Flavio Forni, Maria Angela Vandelli & Giovanni Tosi

  2. Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, Uppsala University Hospital, Uppsala University, SE-75185, Uppsala, Sweden

    Hari S. Sharma & Aruna Sharma

  3. Department Clinical Neurosciences, University Hospital, University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Dafin F. Muresanu

  4. Ever Neuro Pharma, Oberburgau, Austria

    Herbert Mössler

  5. International Experimental CNS Injury and Repair (IECNSIR), Uppsala University Hospital, Frödingsgatan 12, SE-75421, Uppsala, Sweden

    Hari S. Sharma

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  1. Barbara Ruozi
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  2. Daniela Belletti
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  9. Giovanni Tosi
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Correspondence to Hari S. Sharma.

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Ruozi, B., Belletti, D., Sharma, H.S. et al. PLGA Nanoparticles Loaded Cerebrolysin: Studies on Their Preparation and Investigation of the Effect of Storage and Serum Stability with Reference to Traumatic Brain Injury. Mol Neurobiol 52, 899–912 (2015). https://doi.org/10.1007/s12035-015-9235-x

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