Pulsatile protein release from a laminated device comprising polyanhydrides and pH-sensitive complexes.
A laminated device comprising of polyanhydrides as isolating layers and pH-sensitive complexes as protein-loaded layers was designed to deliver proteins in a pulsatile manner. Poly(sebacic anhydride)-b-polyethylene glycol (PSA-b-PEG) and poly(trimellitylimidoglycine-co-sebacic anhydride)-b-polyethylene glycol (P(TMA-gly-co-SA)-b-PEG) were synthesized as isolating layers for their good processing properties at room temperature and suitable erosion duration. During the erosion period, pH of the dissolution fluid decreases to a low value (3.8-5.8). Poly(methacrylic acid)/polyethoxazoline (PMAA/PEOx) complex was used as protein-loaded layers, which could dissociate and release model proteins, Myoglobin (Mb) and Bovine Serum Albumin (BSA), at pH 7.4 while become stable and retained the drugs below pH 5.0. The protein release from the device showed a typical pulsatile fashion. The lag time prior to the pulsatile protein release correlated with the hydrolytic duration of the polyanhydrides, which varied from 30 to 165 h by selecting polyanhydride type and isolating layer thickness. In addition, the pulse duration could be adjusted from 18.5 to 40 h by varying the mass of the complex. The results can be attributed to the synergistic effects between the degrading polyanhydrides, pH-sensitive complexes and proteins.
Jiang
H L
HL
Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, PR China.
Zhu
K J
KJ
D000812:Anhydrides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D009211:Myoglobin / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry
D000812:Anhydrides; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D009211:Myoglobin; C405032:poly(sebacic anhydride)-b-polyethylene glycol; C405033:poly(trimellitylimidoglycine-co-sebacic anhydride)-b-polyethylene glycol; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols