Preparation, characterization and nasal delivery of alpha-cobrotoxin-loaded poly(lactide-co-glycolide)/polyanhydride microspheres.
In this study, alpha-cobrotoxin was incorporated into the microspheres composed of poly(lactide-co-glycolide) (PLGA) and poly[1,3-bis(p-carboxy-phenoxy) propane-co-p-(carboxyethylformamido) benzoic anhydride] (P(CPP:CEFB)) and intranasally delivered to model rats in order to improve its analgesic activity. The microspheres with high entrapment efficiency (>80%) and average diameter of about 25 microm could be prepared by a modified water-in-oil-in-oil (w/o/o) emulsion solvent evaporation method. Scanning electron micrograph (SEM) study indicated that P(CPP:CEFB) content played a considerable role on the morphology and degradation of the microspheres. The presence of P(CPP:CEFB) in the microspheres increased their residence time at the surface of the nasal rat mucosa. The toxicity of the composite microspheres to nasal mucosa was proved to be mild and reversible. A tail flick assay was used to evaluate the antinociceptive activity of the microspheres after nasal administration. Compared with the free alpha-cobrotoxin and PLGA microspheres, PLGA/P(CPP:CEFB) microspheres showed an apparent increase in the strength and duration of the antinociceptive effect at the same dose of alpha-cobrotoxin (80 microg/kg body weight).
Li
Y
Y
Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Jiang
H L
HL
Zhu
K J
KJ
Liu
J H
JH
Hao
Y L
YL
D000281:Administration, Intranasal; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D003039:Cobra Neurotoxin Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D008297:Male; D008863:Microspheres; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000188:drug therapy*; D011098:Polyglactin 910 / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D003039:Cobra Neurotoxin Proteins; D011098:Polyglactin 910; C025154:alpha-cobratoxin