title: Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological) delivery.
abstract: Insulin is a life-saving medication for people with type 1 diabetes, but traditional insulin replacement therapy is based on multiple daily subcutaneous injections or continuous subcutaneous pump-regulated infusion. Nonphysiologic delivery of subcutaneous insulin implies a rapid and sustained increase in systemic insulin levels due to the loss of concentration gradient between portal and systemic circulations. In fact, the liver degrades about half of the endogenous insulin secreted by the pancreas into the venous portal system. The reverse insulin distribution has short- and long-term effects on glucose metabolism. Thus, researchers have explored less-invasive administration routes based on innovative pharmaceutical formulations, which preserve hormone stability and ensure the therapeutic effectiveness. This review examines some of the recent proposals from clinical and material chemistry point of view, giving particular attention to patients' (and diabetologists') ideal requirements that organic chemistry could meet.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Matteucci
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Siena, Italy.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Giampietro
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Pisa, Siena, Italy.
authors.forename: Vera
authors.initials: V
authors.lastname: Covolan
authors.affiliation: Department of Life Sciences, Laboratory of Pharmacology and Toxicology, University of Siena, Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giustarini
authors.affiliation: Division of Nephrology, University of Texas Health Science Center San Antonio, South Texas Veteran Health Care System, San Antonio, Texas, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fanti
authors.affiliation: Department of Life Sciences, Laboratory of Pharmacology and Toxicology, University of Siena, Siena, Italy.
authors.forename: Ranieri
authors.initials: R
authors.lastname: Rossi
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D016503:Drug Delivery Systems; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D000078790:Insulin Secretion
chemical_list: D007328:Insulin
keywords: biodegradable polymers; drug administration routes; drug formulations; insulin; nanoparticles; portal system; type 1 diabetes mellitus