Improvement of cationic albumin conjugated pegylated nanoparticles holding NC-1900, a vasopressin fragment analog, in memory deficits induced by scopolamine in mice.

Abstract

NC-1900, an active fragment analog of arginine vasopressin [arginine vasopressin-(4-9)], has proved to be capable of improving the spatial memory deficits and the impairments in passive avoidance test. In this study, a novel drug carrier for brain delivery, cationic bovine serum albumin conjugated pegylated nanoparticles (CBSA-NPs) holding NC-1900, was developed and its improvement on scopolamine-induced memory deficits was investigated in mice using the platform-jumping avoidance test. CBSA-NPs loaded with NC-1900 in spherical shape and uniform size below 100 nm were prepared by the double emulsion/solvent evaporation procedure, and the zeta potential of CBSA-NPs was about -8mV with the loading capacity of NC-1900 around 0.46%. The in vitro study showed that approximately 10% NC-1900 was released from CBSA-NPs in pH 7.4 phosphate buffer saline (PBS) during 56 h incubation with about 15% NC-1900 released in pH 4.0 PBS during 7 days, indicating the sustained release of this carrier. Furthermore, the half-life of NC-1900 loaded in CBSA-NPs in plasma was about 78 h, which was 4-fold longer than that of free NC-1900 (19 h). The active avoidance behavioral results showed that the s.c. administration of NC-1900 tended to improve memory deficits, but the difference did not present any statistical significance, whereas this peptide failed to produce any positive effects by i.v. administration. However, the i.v. injection of CBSA-NPs loaded with NC-1900 greatly improved memory impairments to a normal level, but the efficacy was slight if the loaded nanoparticles (NPs) were exclusive of the conjugation of CBSA, indicating that CBSA-NP was a promising brain delivery carrier for NC-1900 with CBSA as a potent brain targetor. It was concluded that CBSA-NP loaded with NC-1900 was potentially efficacious in the treatment of memory deficits via i.v. administration.

• Authors: Yue-Ling Xie, Wei Lu, Xin-Guo Jiang
• Journal: Behavioural brain research (Behav Brain Res) Vol. 173 Issue 1 Pg. 76-84 (Oct 02 2006) ISSN: 0166-4328 [Print] Netherlands
• PMID: 16828890 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Validation Study)

Chemical References

• Drug Carriers
• NC 1900
• Nootropic Agents
• Oligopeptides
• Peptide Fragments
• Arginine Vasopressin
• Serum Albumin, Bovine
• Polyethylene Glycols
• argipressin (4-9)
• Scopolamine
• Pyrrolidonecarboxylic Acid

Topics

• Animals
• Arginine Vasopressin (administration & dosage, analogs & derivatives, pharmacokinetics, physiology)
• Avoidance Learning (drug effects, physiology)
• Drug Carriers
• Drug Delivery Systems
• Male
• Memory (physiology)
• Memory Disorders (chemically induced, drug therapy)
• Mice
• Nanostructures
• Nootropic Agents (administration & dosage, pharmacokinetics)
• Oligopeptides (administration & dosage, pharmacokinetics)
• Particle Size
• Peptide Fragments (administration & dosage, pharmacokinetics, physiology)
• Polyethylene Glycols (administration & dosage, chemistry)
• Pyrrolidonecarboxylic Acid (administration & dosage, analogs & derivatives, pharmacokinetics)
• Random Allocation
• Scopolamine
• Serum Albumin, Bovine (administration & dosage, chemistry)