Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents

Abstract

Please cite this article as: R. Cavalli, M. Argenziano, E. Vigna, P. Giustetto, E. Torres, S. Aime, E. Terreno, Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents, Colloids and Surfaces B: Biointerfaces (2015), http://dx.doi.org/10. 1016/j.colsurfb.2015.03.023 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 27 A c c e p t e d M a n u s c r i p A c c e p t e d M a n u s c r i p t 2 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 500 nm 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 anticancer treatments.

Chitosan‐based multifunctional nanomedicines and theranostics for targeted therapy of cancer

“…A theranostic system provides imaging/diagnostics and therapeutic functions simultaneously . An image‐guided smart NPs is expected to provide a suitable platform for spatial and temporal controlled delivery systems .…”

“…Nanobubbles (NBs) are another promising candidate in drug delivery because these agents can circulate in the blood capillaries and easily cross the porous TMV in the TME and reach the tumor cells. NBs are spherical particles with a core–shell structure filled up with a gas, which gives them acoustic‐activated feature . As bubbles of submicron size, they are mainly prepared to increase the stability and improve the biodistribution of the carried drug to the pathological site.…”

“…A theranostic system provides imaging/diagnostics and therapeutic functions simultaneously. 6,112,113 An image-guided smart NPs is expected to provide a suitable platform for spatial and temporal controlled delivery systems. [114][115][116][117] Combined delivery of therapeutic and diagnostic agents with a single system using nanoscaled theranostic approaches paves the way for the development of tailored NSs for the early diagnosis and prevention of formidable disease and their precise detection and therapy.…”

“…NBs are spherical particles with a core-shell structure filled up with a gas, which gives them acoustic-activated feature. 113,[189][190][191] As bubbles of submicron size, they are mainly prepared to increase the stability and improve the biodistribution of the carried drug to the pathological site. These platforms can also be regarded as the theranostics.…”

Tri-Needle Coaxial Electrospray Engineering of Magnetic Polymer Yolk–Shell Particles Possessing Dual-Imaging Modality, Multiagent Compartments, and Trigger Release Potential

“…[3][4][5] Furthermore, the functionality of such particles goes beyond image-guided drug delivery; in that rapid assessment and treatment of disease is accomplished at an early stage whilst minimizing unwanted cytotoxic side-effects often arising from conventional strategies. [6][7] Magnetic resonance imaging (MRI) is a pain-free and safe diagnostic procedure that has numerous advantages over other routine imaging methods including excellent anatomic detail, exquisite soft tissue contrast, high spatial resolution and multi-planar imaging capacity. [8][9] MRI signal is dependent on longitudinal (T 1 ) and transverse (T 2 ) proton relaxation times of water (mainly) and therefore; differences arising in these values provide variable contrast in images.…”