Preparation and evaluation of anti-neuroexcitation peptide (ANEP) loaded N-trimethyl chitosan chloride nanoparticles for brain-targeting.
Anti-neuroexcitation peptide (ANEP) is a promising candidate for the treatment of neuroexcitation-associated diseases. N-Trimethyl chitosan (TMC) with different degrees of quaternization was synthesized, characterized and evaluated as a brain-targeting delivery vehicle for ANEP. ANEP-loaded TMC nanoparticles were prepared by ionic crosslinking of TMC with tripolyphosphate (TPP). The optimized formulation of nanoparticles consisted of TMC with a degree of quaternization (DQ) of 36.1% and TPP solution with a concentration of 0.6 mg/mL. The mean encapsulation efficiency and loading capacity of the optimum formulation was 80.63% and 185.4 microg/mL, respectively, while the mean particle size, zeta potential, and pH value were 255 nm, 32.0 mV and 6.61, respectively. ANEP was labeled with FITC for in vivo tissue distribution experiments. The results showed that the targetability of ANEP to brain was significantly increased by TMC nanoparticles. Absorptive-mediated transcytosis was believed to be the main pathway for the brain-targeting of FITC-ANEP-TMC/NPs. These findings demonstrate that TMC nanoparticles are potentially useful brain-targeting delivery systems for ANEP.
Wang
Siling
S
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China. wangslsy@163.com
Jiang
Tongying
T
Ma
Mingxin
M
Hu
Yanchen
Y
Zhang
Jinghai
J
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles; D036103:Nanotechnology; D010539:Permeability; D011122:Polyphosphates / Q000737:chemistry; D055550:Protein Stability; D012604:Scorpion Venoms / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution
D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005456:Fluorescent Dyes; C118071:N-trimethyl chitosan chloride; D011122:Polyphosphates; D012604:Scorpion Venoms; C058792:anti-epilepsy peptide, Buthrus martensii; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate; C005692:triphosphoric acid