title: Protamine modified metal ion-protein chelate microparticles for sustained release of interferon.
abstract: This study focuses on extending the release period of zinc-protein chelate through protamine modification. Recombinant human interferon-α-2b (rhIFN), a highly pleiotropic cytokine with a short intrinsic pharmacokinetic half-life when injected subcutaneously (∼2-6 h), was used as a model drug. Protamine modified zinc-rhIFN chelate microparticles were prepared by co-precipitating rhIFN with zinc and protamine. Introduction of protamine (2.5-20 mg/mL) into the chelation system had several prominent effects. First, percentage of chelated rhIFN was lowered (from >99% to ∼90%); second, particle size was gradually increased (from ∼0.45 μm to ∼2 μm); last but important, it extended the release period of the chelate both in vitro (complete release was retarded from 8 h to 48 h) and in vivo (t(1/2) was prolonged from 4.5 h to 15.5 h and mean residence time from 9.4 h to 29.6 h). Size-exclusion liquid chromatography and cytopathic effect inhibition assay indicated rhIFN preserved its structural and functional integrity in these chelates.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Jiang
authors.forename: Kai
authors.initials: K
authors.lastname: Shi
authors.forename: Dengning
authors.initials: D
authors.lastname: Xia
authors.forename: Hongze
authors.initials: H
authors.lastname: Piao
authors.forename: Peng
authors.initials: P
authors.lastname: Quan
authors.forename: Tao
authors.initials: T
authors.lastname: Song
authors.forename: Fude
authors.initials: F
authors.lastname: Cui
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002850:Chromatography, Gel; D003692:Delayed-Action Preparations; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D008863:Microspheres; D010316:Particle Size; D011479:Protamines / Q000737:chemistry*; D011817:Rabbits; D011994:Recombinant Proteins; D013997:Time Factors; D015032:Zinc / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011479:Protamines; D011994:Recombinant Proteins; D015032:Zinc