Long-Circulating Hyaluronan-Based Nanohydrogels as Carriers of Hydrophobic Drugs
Chiara Di Meo,
Mayte Martínez-Martínez,
Tommasina Coviello,
Marival Bermejo,
Virginia Merino,
Isabel Gonzalez-Alvarez,
Marta Gonzalez-Alvarez,
Pietro Matricardi
Affiliations
Chiara Di Meo
Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Mayte Martínez-Martínez
Department of Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, San Juan de Alicante, 03550 Alicante, Spain
Tommasina Coviello
Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Marival Bermejo
Department of Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, San Juan de Alicante, 03550 Alicante, Spain
Virginia Merino
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, 46100 Burjassot, Spain
Isabel Gonzalez-Alvarez
Department of Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, San Juan de Alicante, 03550 Alicante, Spain
Marta Gonzalez-Alvarez
Department of Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, San Juan de Alicante, 03550 Alicante, Spain
Pietro Matricardi
Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Nanohydrogels based on natural polymers, such as polysaccharides, are gaining interest as vehicles for therapeutic agents, as they can modify the pharmacokinetics and pharmacodynamics of the carried drugs. In this work, hyaluronan-riboflavin nanohydrogels were tested in vivo in healthy rats highlighting their lack of toxicity, even at high doses, and their different biodistribution with respect to that of native hyaluronan. They were also exploited as carriers of a hydrophobic model drug, the anti-inflammatory piroxicam, that was physically embedded within the nanohydrogels by an autoclave treatment. The nanoformulation was tested by intravenous administration showing an improvement of the pharmacokinetic parameters of the molecule. The obtained results indicate that hyaluronan-based self-assembled nanohydrogels are suitable systems for low-soluble drug administration, by increasing the dose as well as the circulation time of poorly available therapeutic agents.
