title: Transdermal delivery of aminoglycosides: amikacin transport and iontophoretic non-invasive monitoring.
abstract: The aim of this paper was to try to single out new administration strategies for aminoglycoside antibiotics. The objectives of the work were to reduce the systemic absorption in the case of topical application and to achieve plasma levels within the therapeutic window in case of systemic administration. Amikacin (AK) was chosen as a model aminoglycoside, as it has a broad spectrum of activity against Gram-negative bacteria. Additionally, since the therapeutic use of aminoglycosides requires careful monitoring, the feasibility of noninvasive monitoring of AK by reverse iontophoresis was explored in preliminary experiments. Permeation experiments were performed in vitro using rabbit ear skin as barrier. From the results obtained, it can be concluded that topical delivery of amikacin is possible for the treatment of local diseases, both using a commercial gel formulation and an innovative transdermal film, the latter being able to reduce in a significant way the risks of systemic absorption. When anodal iontophoresis at pH 4.0 was applied, amikacin transport and, to a limited extent, accumulation were increased. Reverse iontophoresis gave promising results, since AK could be extracted across the skin at the cathode, and this can be taken as a reference point to develop and optimize the technique.
authors.affiliation: Dipartimento Farmaceutico, Università degli Studi di Parma, Parco Area delle Scienze 27/A, 43100 Parma, Italy. patrizia.santi@unipr.it
authors.forename: Sara
authors.initials: S
authors.lastname: Nicoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Santi
mesh_terms: D000279:Administration, Cutaneous; D000583:Amikacin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000617:Aminoglycosides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001692:Biological Transport; D016903:Drug Monitoring / Q000379:methods; D004431:Ear, External / Q000378:metabolism; D005782:Gels; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods; D011817:Rabbits; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012996:Solutions; D013997:Time Factors
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005782:Gels; D012996:Solutions; D000583:Amikacin