PLGA Nanoparticles Loaded Cerebrolysin: Studies on Their Preparation and Investigation of the Effect of Storage and Serum Stability with Reference to Traumatic Brain Injury

被引:53
作者
Ruozi, Barbara [1 ]
Belletti, Daniela [1 ]
Sharma, Hari S. [2 ,5 ]
Sharma, Aruna [2 ]
Muresanu, Dafin F. [3 ]
Moessler, Herbert [4 ]
Forni, Flavio [1 ]
Vandelli, Maria Angela [1 ]
Tosi, Giovanni [1 ]
机构
[1] Univ Modena & Reggio Emilia, Dept Life Sci, Lab Pharmaceut Technol, I-41125 Modena, Italy
[2] Uppsala Univ, Univ Uppsala Hosp, Dept Surg Sci Anaesthesiol & Intens Care Med, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden
[3] Univ Med & Pharm, Univ Hosp, Dept Clin Neurosci, Cluj Napoca, Romania
[4] Ever Neuro Pharma, Oberburgau, Austria
[5] Univ Uppsala Hosp, IECNSIR, SE-75421 Uppsala, Sweden
基金
英国医学研究理事会;
关键词
Nanoparticles (NPs); Polylactic-co-glycolide (PLGA); Cerebrolysin; Long-termstability; Serumstability; Traumatic brain injury; Neuroprotection; WHOLE-BODY HYPERTHERMIA; CEREBRAL BLOOD-FLOW; NORMOTENSIVE YOUNG-RATS; SPINAL-CORD-INJURY; BARRIER PERMEABILITY; NEUROTROPHIC FACTORS; SOLVENT EVAPORATION; EDEMA FORMATION; DRUG-DELIVERY; 5-HT LEVEL;
D O I
10.1007/s12035-015-9235-x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:899 / 912
页数:14
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