title: Epsilon-poly-L-lysine guided improving pulmonary delivery of supramolecular self-assembled insulin nanospheres.
abstract: This work presents new spherical nanoparticles that are fabricated from supramolecular self-assembly of therapeutic proteins for inhalation treatment. The formation involved self-assembly of insulin into nanospheres (INS) by a novel thermal induced phase separation method. Surface functional modification of INS with ɛ-poly-L-lysine (EPL), a homopolymerized cationic peptide, was followed to form a core-shell structure (INS@EPL). Both INS and INS@EPL were characterized as spherical particles with mean diameter size of 150-250 nm. The process of transient thermal treatment did not change their biological potency retention significantly. FTIR and CD characterizations indicated that their secondary structures and biological potencies were not changed significantly after self-assembly. The in vivo investigation after pulmonary administration, including lung deposition, alveoli distribution, pharmacological effects and serum pharmacokinetics were investigated. Compared to that of INS, intratracheal administration of INS@EPL offered a pronounced and prolonged lung distribution, as well as pharmacological effects which were indicated by the 23.4% vs 11.7% of relative bioavailability. Accordingly, the work described here demonstrates the possibility of spherical supramolecular self-assembly of therapeutic proteins in nano-scale for pulmonary delivery application.
authors.affiliation: School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address: kaishi_syphu@hotmail.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Ke
authors.affiliation: School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: National Institutes for Food and Drug Control (NIFDC), No. 2, Tiantan Xili, Beijing 100050, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Fude
authors.initials: F
authors.lastname: Cui
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002942:Circular Dichroism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D016503:Drug Delivery Systems; D007328:Insulin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008168:Lung / Q000378:metabolism*; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D011107:Polylysine / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D034421:Sus scrofa; D014961:X-Ray Diffraction
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011107:Polylysine
keywords: Insulin; Nanospheres; ɛ-Poly-l-lysine