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      Echographic and physical characterization of albumin-stabilized nanobubbles

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          Abstract

          There has been increasing interest in using nanobubbles (NBs) for ultrasound mediated drug delivery as well as for ultrasound imaging. Albumin NBs are especially attractive for its potential of becoming a versatile platform for drug carriers and molecular targeted therapy agents. However, physical characterization of NBs is generally considered to be difficult due to various technical issues, such as concentration limitations, nanoparticle contamination, etc. In the present study, we measured the size distribution, concentration and weight density of albumin stabilized NBs by means of multiple nanoscale measurement modalities. Laser nanoparticle tracking analysis, multicolor flow cytometry, resonance mass evaluation showed consistent measurement results of the NBs with low mass weight density and diameter size ranging from 100 nm to 400 nm. Furthermore, the NB solution showed excellent images by high frequency ultrasound (30–50 MHz) in flow model acoustic phantoms. The NBs also induced acute cell disruption by low intensity ultrasound (0.8 W/cm 2) irradiation. We successfully fabricated and characterized albumin stabilized NBs which could serve as an effective platform for future theranositic agents.

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          A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.

          Y Matsumura, H. Maeda (1986)
          We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.
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            Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles.

            Felix Kratz (2008)
            Albumin is playing an increasing role as a drug carrier in the clinical setting. Principally, three drug delivery technologies can be distinguished: coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugation with bioactive proteins and encapsulation of drugs into albumin nanoparticles. The accumulation of albumin in solid tumors forms the rationale for developing albumin-based drug delivery systems for tumor targeting. Clinically, a methotrexate-albumin conjugate, an albumin-binding prodrug of doxorubicin, i.e. the (6-maleimido)caproylhydrazone derivative of doxorubicin (DOXO-EMCH), and an albumin paclitaxel nanoparticle (Abraxane) have been evaluated clinically. Abraxane has been approved for treating metastatic breast cancer. An alternative strategy is to bind a therapeutic peptide or protein covalently or physically to albumin to enhance its stability and half-life. This approach has been applied to peptides with antinociceptive, antidiabetes, antitumor or antiviral activity: Levemir, a myristic acid derivative of insulin that binds to the fatty acid binding sites of circulating albumin, has been approved for the treatment of diabetes. Furthermore, Albuferon, a fusion protein of albumin and interferon, is currently being assessed in phase III clinical trials for the treatment of hepatitis C and could become an alternative to pegylated interferon. This review gives an account of the different drug delivery systems which make use of albumin as a drug carrier with a focus on those systems that have reached an advanced stage of preclinical evaluation or that have entered clinical trials.
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              A History of Nanobubbles.

              Muidh Alheshibri, Jing Qian, Marie Jehannin … (2016)
              We follow the history of nanobubbles from the earliest experiments pointing to their existence to recent years. We cover the effect of Laplace pressure on the thermodynamic stability of nanobubbles and why this implies that nanobubbles are thermodynamically never stable. Therefore, understanding bubble stability becomes a consideration of the rate of bubble dissolution, so the dominant approach to understanding this is discussed. Bulk nanobubbles (or fine bubbles) are treated separately from surface nanobubbles as this reflects their separate histories. For each class of nanobubbles, we look at the early evidence for their existence, methods for the production and characterization of nanobubbles, evidence that they are indeed gaseous, or otherwise, and theories for their stability. We also look at applications of both surface and bulk nanobubbles.
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                Author and article information

                Contributors
                Katsuro Tachibana
                Journal
                Journal ID (nlm-ta): Heliyon
                Journal ID (iso-abbrev): Heliyon
                Title: Heliyon
                Publisher: Elsevier
                ISSN (Electronic): 2405-8440
                Publication date PMC-release: 17 June 2019
                Publication date Collection: June 2019
                Publication date (Electronic): 17 June 2019
                Volume: 5
                Issue: 6
                Electronic Location Identifier: e01907
                Affiliations
                [1]Department of Anatomy, Fukuoka University School of Medicine, Fukuoka, 814-0180, Japan
                Author notes
                [∗ ]Corresponding author. k-tachi@ 123456fukuoka-u.ac.jp
                Article
                Publisher ID: S2405-8440(18)39119-9 Publisher ID: e01907
                DOI: 10.1016/j.heliyon.2019.e01907
                PMC ID: 6584773
                SO-VID: 0e3b1c17-01db-43e1-add5-363d94992ece
                Copyright © © 2019 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 25 December 2018
                Date revision received : 26 March 2019
                Date accepted : 3 June 2019
                Categories
                Subject: Article

                Keywords: nanotechnology
                Data availability:
                Keywords: nanotechnology

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