title: Hyaluronan-cholesterol nanohydrogels: Characterisation and effectiveness in carrying alginate lyase.
abstract: Although in recent years several methods have been studied and developed to obtain different types of nanosized drug delivery systems, the set up of suitable procedures and materials remains highly expensive, their preparation is time consuming and often not feasible for a scale-up process. Furthermore, the sterilisation and storage of nanocarrier formulations represents a complicated but mandatory step for their effective use. In our previous work we assessed the use of an autoclaving process to achieve, in one simple step, sterile self-assembled hyaluronan-cholesterol (HA-CH) and hyaluronan-riboflavin (HA-Rfv) nanohydrogels (NHs). In the present work, the effect of the high temperature on HA-CH has been studied in detail. HA-CH suspensions were characterised in terms of size and polydispersity by Dynamic Light Scattering at different temperatures and conditions; the HA-CH chemical structure and its molecular weight were assessed via FT-IR and GPC analysis after the sterilising cycle in an autoclave at 121°C for 20min. The obtained NHs were then observed with TEM and AFM microscopy, in both dry and liquid conditions. The Young's modulus of the NHs was determined, evidencing the soft nature of these nanosystems; the critical aggregation concentration (c.a.c) of the nanosuspension was also assessed. Thereafter, alginate lyase (AL) was conjugated to NHs, with the aim of developing a useful system for therapies against bacterial infections producing alginate biofilms. The conjugation efficiency and the enzymatic activity of AL were determined after immobilisation. The AL-NHs system showed the ability to depolymerise alginate, offering an opportunity to be a useful nanosystem for the treatment of biofilm-associated infections.
authors: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors: Elita
authors: E
authors: Montanari
authors: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors: Chiara
authors: C
authors: Di Meo
authors: Institute for Complex Systems, National Research Council, Via dei Taurini 19, 00185 Rome, Italy; Physics Department, Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy.
authors: Simona
authors: S
authors: Sennato
authors: Department of Biochemical Sciences, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors: Antonio
authors: A
authors: Francioso
authors: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors: Anna Laura
authors: AL
authors: Marinelli
authors: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; Institute for Complex Systems, National Research Council, Via dei Taurini 19, 00185 Rome, Italy; Physics Department, Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy.
authors: Francesca
authors: F
authors: Ranzo
authors: Department of Public Health and Infectious Diseases, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors: Serena
authors: S
authors: Schippa
authors: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors: Tommasina
authors: T
authors: Coviello
authors: Institute for Complex Systems, National Research Council, Via dei Taurini 19, 00185 Rome, Italy; Physics Department, Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy.
authors: Federico
authors: F
authors: Bordi
authors: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy. Electronic address: pietro.matricardi@uniroma1.it.
authors: Pietro
authors: P
authors: Matricardi
mesh_terms: D000464:Alginates / Q000378:metabolism; D001424:Bacterial Infections / Q000378:metabolism / Q000382:microbiology / Q000628:therapy; D018441:Biofilms; D001709:Biotechnology; D002784:Cholesterol / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D020100:Hydrogels; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D011133:Polysaccharide-Lyases / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D000464:Alginates; D004337:Drug Carriers; D020100:Hydrogels; D006820:Hyaluronic Acid; D002784:Cholesterol; D011133:Polysaccharide-Lyases; C016158:poly(beta-D-mannuronate) lyase
keywords: Alginate lyase; Hyaluronan; Nanohydrogel; Protein delivery; Self-assembly