title: Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents.
abstract: Theranostic delivery systems are nanostructures that combine the modality of therapy and diagnostic imaging. Polymeric micro- and nanobubbles, spherical vesicles containing a gas core, have been proposed as new theranostic carriers for MRI-guided therapy. In this study, chitosan nanobubbles were purposely tuned for the co-delivery of prednisolone phosphate and a Gd(III) complex, as therapeutic and MRI diagnostic agent, respectively. Perfluoropentane was used for filling up the internal core of the formulation. These theranostic nanobubbles showed diameters of about 500nm and a positive surface charge that allows the interaction with the negatively charged Gd-DOTP complex. Pluronic F68 was added to the nanobubble aqueous suspension as stabilizer agent. The encapsulation efficiency was good for both the active compounds, and a prolonged drug release profile was observed in vitro. The effect of ultrasound stimulation on prednisolone phosphate release was evaluated at 37°C. A marked increase on drug release kinetics with no burst effect was obtained after the exposure of the system to ultrasound. Furthermore, the relaxivity of the MRI probe changed upon incorporation in the nanobubble shell, thereby offering interesting opportunity in dual MRI-US experiments. The ultrasound characterization showed a good in vitro echogenicity of the theranostic nanobubbles. In summary, chitosan drug-loaded nanobubbles with Gd(III) complex bound to their shell might be considered a new platform for imaging and drug delivery with the potential of improving anti-cancer treatments.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via P. Giuria 9, 10125 Torino, Italy. Electronic address: roberta.cavalli@unito.it.
authors.forename: R
authors.initials: R
authors.lastname: Cavalli
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via P. Giuria 9, 10125 Torino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Argenziano
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via P. Giuria 9, 10125 Torino, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Vigna
authors.affiliation: Dipartimento di Biotecnologie Molecolari e Scienze della Salute, Centro di Imaging Molecolare e Preclinico, Università degli Studi di Torino, via Nizza 52, 10126 Torino, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Giustetto
authors.affiliation: Dipartimento di Biotecnologie Molecolari e Scienze della Salute, Centro di Imaging Molecolare e Preclinico, Università degli Studi di Torino, via Nizza 52, 10126 Torino, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Torres
authors.affiliation: Dipartimento di Biotecnologie Molecolari e Scienze della Salute, Centro di Imaging Molecolare e Preclinico, Università degli Studi di Torino, via Nizza 52, 10126 Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Aime
authors.affiliation: Dipartimento di Biotecnologie Molecolari e Scienze della Salute, Centro di Imaging Molecolare e Preclinico, Università degli Studi di Torino, via Nizza 52, 10126 Torino, Italy. Electronic address: enzo.terreno@unito.it.
authors.forename: E
authors.initials: E
authors.lastname: Terreno
mesh_terms: D048271:Chitosan / Q000737:chemistry*; D003287:Contrast Media / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005466:Fluorocarbons / Q000494:pharmacology*; D006454:Hemoglobins / Q000032:analysis; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D045423:Microbubbles; D049329:Nanostructures / Q000737:chemistry; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics; D000068936:Theranostic Nanomedicine; D014018:Tissue Distribution; D014465:Ultrasonics; D010420:Pentanes
chemical_list: D048271:Chitosan; D003287:Contrast Media; D005466:Fluorocarbons; D006454:Hemoglobins; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C059412:gadolinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetrakis(methylenephosphonic acid); C008806:perfluoropentane; D010420:Pentanes
keywords: Controlled release; Gd complex; MRI; Nanobubbles; Theranosis; Ultrasound