title: Polycationic peptide guided spherical ordered self-assembly of biomacromolecules.
abstract: Achieving effective controllable delivery of therapeutic biomacromolecules for long action without new molecular entities generation or carriers employed offers a promising alternative and significant clinical benefit. We show here that recombinant human interferon-alpha (rhIFN) can form a three dimensional ordered structure that is featured by spherical semi-crystalline through molecular self-assembly directed by a polycationic short peptide. The phase diagrams for self-assembly were constructed to identify the optimal regions for nucleation and ordered growth, and which were followed by the physico-chemical characterization of the ordered self-assemblies, including morphology, particle size, X-ray diffraction, circular dichroism and biological potency evaluations. With varied molar ratio of the two composed biomacromolecules, the dissolution behaviors of the self-assemblies could be manipulated in vitro and in vivo. The plasma pharmacokinetics suggested that s.c. administration of self-assemblies at the specified relative proportion of rhIFN to polycationic peptide offered a significant prolonged duration time of rhIFN blood levels up to seven days. Moreover, molecular simulation was performed to better understand their binding site and mode. The work described here demonstrates the possibility of spherical ordered self-assembly of biomacromolecules for controllable delivery application of therapeutic proteins.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. kaishi_syphu@hotmail.com
authors.forename: Kai
authors.initials: K
authors.lastname: Shi
authors.forename: Fude
authors.initials: F
authors.lastname: Cui
authors.forename: Hongshu
authors.initials: H
authors.lastname: Bi
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Song
mesh_terms: D002942:Circular Dichroism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D000071228:Polyelectrolytes; D011994:Recombinant Proteins / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D016898:Interferon-alpha; D010455:Peptides; D011073:Polyamines; D000071228:Polyelectrolytes; D011994:Recombinant Proteins