Intranasal delivery of ciprofloxacin to rats: A topical approach using a thermoreversible in situ gel.
Intranasal administration of antibiotics is an alternative and attractive delivery approach in the treatment of local infections such as chronic rhinosinusitis. This topical route has the advantage of delivering high drug concentrations directly to the site of infection when trying to eradicate the highly resistant bacterial biofilms. The purpose of this study was to assess and compare the pharmacokinetic parameters of ciprofloxacin following intranasal and intravenous administrations to rats in plasma, olfactory bulb and nasal mucosa of two different nasal regions. For intranasal administration a thermoreversible in situ gel was used to increase drug residence time in nasal cavity. Ciprofloxacin concentration time-profile in nasal mucosa of the studied anterior region (at naso- and maxilloturbinates level) was markedly higher after intranasal administration (0.24mg/kg) than that following intravenous administration (10mg/kg), while in nasal mucosa of the more posterior region (at ethmoidal turbinates level) ciprofloxacin concentrations were found to be higher after intranasal administration when the different dose administered by both routes is taken into account. A plateau in ciprofloxacin concentration was observed in nasal mucosa of both studied regions after intranasal administration, suggesting a slow delivery of the drug over a period of time using the nasal gel formulation. In plasma and olfactory bulb, concentration of ciprofloxacin was residual after intranasal administration, which demonstrates this is a safe administration route by preventing systemic and particularly central nervous system adverse effects. Dose-normalized pharmacokinetic parameters of ciprofloxacin exposure to nasal mucosa revealed higher values after intranasal delivery not only in the anterior region but also in the posterior nasal region. In conclusion, topical intranasal administration appears to be advantageous for delivering ciprofloxacin to the biophase, with negligible systemic and brain exposure using a 41.7-fold lower dose than intravenous administration. Therefore, it may represent a promising approach in the drug management of chronic rhinosinusitis.
Pharmacology Department, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
Joana
J
Sousa
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Rua Marquês d'Ávila e Bolama, 6201-001 Covilhã, Portugal. Electronic address: gilberto@fcsaude.ubi.pt.
Gilberto
G
Alves
Pharmacology Department, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
Paula
P
Oliveira
Pharmacology Department, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
Ana
A
Fortuna
Pharmacology Department, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
Amílcar
A
Falcão
D000281:Administration, Intranasal; D000287:Administration, Topical; D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005782:Gels; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D005782:Gels; D002939:Ciprofloxacin
Intranasal administration; Nasal mucosa; Pharmacokinetics; Rat; Topical ciprofloxacin