title: A Nanoscale Polymeric Penetration Enhancer Based on Polylysine for Topical Delivery of Proteins and Peptides.
abstract: To overcome the chemical penetration enhancer-associated toxicities, without sacrificing delivery efficiency, a functional ε-polylysine (EPL-g-Cetyl) as polymeric permeation enhancers was synthesized by the hydrophobic modification of amino groups of ε-polylysine. The obtained EPL-g-Cetyl nanoparticles had about 200 nm in size with narrower distribution, high positive charge, and good stability. A high loading capacity (up to 17%) of the formulation provided a sustained and controlled release pattern of insulin from the nanoparticles. Importantly, in vivo study validates that the nanoparticles were able to penetrate stratum corneum, even reaching to the dermis, and insulin was delivered in its active state. Furthermore, EPL-g-Cetyl with the highest degree of substitution was found to be low toxicity to NIH 3T3 and Chinese hamster ovary cells. There was no significant loss in the integrity of the epidermis after drug and enhancer treatment. The novel polylysine derivative as carrier has a potential application for topical delivery of proteins and peptides.
authors.affiliation: Department of Endocrinology, Tianjin Hospital, Tianjin 300211, China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Luo
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: The Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China.
authors.forename: Xinge
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China. Electronic address: wuzhongming@tmu.edu.cn.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D011107:Polylysine / Q000008:administration & dosage / Q000378:metabolism*; D011108:Polymers / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000502:physiology*
chemical_list: D007328:Insulin; D011108:Polymers; D011107:Polylysine
keywords: cell viability; polylysine; polymeric penetration enhancers; proteins and peptides; topical delivery