A novel gel based on an ionic complex from a dendronized polymer and ciprofloxacin: Evaluation of its use for controlled topical drug release.
The development and characterization of a novel, gel-type material based on a dendronized polymer (DP) loaded with ciprofloxacin (CIP), and the evaluation of its possible use for controlled drug release, are presented in this work. DP showed biocompatible and non-toxic behaviors in cultured cells, both of which are considered optimal properties for the design of a final material for biomedical applications. These results were encouraging for the use of the polymer loaded with CIP (as a drug model), under gel form, in the development of a new controlled-release system to be evaluated for topical administration. First, DP-CIP ionic complexes were obtained by an acid-base reaction using the high density of carboxylic acid groups of the DP and the amine groups of the CIP. The complexes obtained in the solid state were broadly characterized using FTIR spectroscopy, XRP diffraction, DSC-TG analysis and optical microscopy techniques. Gels based on the DP-CIP complexes were easily prepared and presented excellent mechanical behaviors. In addition, optimal properties for application on mucosal membranes and skin were achieved due to their high biocompatibility and acute skin non-irritation. Slow and sustained release of CIP toward simulated physiological fluids was observed in the assays (in vitro), attributed to ion exchange phenomenon and to the drug reservoir effect. An in vitro bacterial growth inhibition assay showed significant CIP activity, corresponding to 38 and 58% of that exhibited by a CIP hydrochloride solution at similar CIP concentrations, against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. However, CIP delivery was appropriate, both in terms of magnitude and velocity to allow for a bactericidal effect. In conclusion, the final product showed promising behavior, which could be exploited for the treatment of topical and mucosal opportunistic infections in human or veterinary applications.
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
Mónica C
MC
García
Instituto de Desarrollo Tecnológico para la Industria Química (INTEC), CONICET, Colectora Ruta Nac. N° 168, km. 0, Pje. El Pozo, 3000 Santa Fe, Argentina.
Julio C
JC
Cuggino
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
Clarisa I
CI
Rosset
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
Paulina L
PL
Páez
Instituto Multidisciplinario de Biología Vegetal (IMBIV), CONICET and Laboratorio de Materiales Poliméricos (LAMAP), Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
Miriam C
MC
Strumia
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
Ruben H
RH
Manzo
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
Fabiana L
FL
Alovero
Instituto Multidisciplinario de Biología Vegetal (IMBIV), CONICET and Laboratorio de Materiales Poliméricos (LAMAP), Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
Cecilia I
CI
Alvarez Igarzabal
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina. Electronic address: alvaro@fcq.unc.edu.ar.
Alvaro F
AF
Jimenez-Kairuz
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002939:Ciprofloxacin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D005782:Gels / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D011108:Polymers / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011817:Rabbits; D012212:Rheology; D012867:Skin / Q000187:drug effects; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D050091:Dendrimers; D004337:Drug Carriers; D005782:Gels; D007477:Ions; D011108:Polymers; D002939:Ciprofloxacin
Ciprofloxacin; Dendronized polymer; Drug controlled release; Hydrogel; Polyelectrolyte-drug complexes