Nanostructured Polymeric, Liposomal and Other Materials to Control the Drug Delivery for Cardiovascular Diseases

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Abstract

Cardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated 17.9 million lives each year, representing one third of global mortality. As existing therapies still have limited success, due to the inability to control the biodistribution of the currently approved drugs, the quality of life of these patients is modest. The advent of nanomedicine has brought new insights in innovative treatment strategies. For this reason, several novel nanotechnologies have been developed for both targeted and prolonged delivery of therapeutics to the cardiovascular system tο minimize side effects. In this regard, nanoparticles made of natural and/or synthetic nanomaterials, like liposomes, polymers or inorganic materials, are emerging alternatives for the encapsulation of already approved drugs to control their delivery in a targeted way. Therefore, nanomedicine has attracted the attention of the scientific community as a potential platform to deliver therapeutics to the injured heart. In this review, we discuss the current types of biomaterials that have been investigated as potential therapeutic interventions for CVDs as they open up a host of possibilities for more targeted and effective therapies, as well as minimally invasive treatments.

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Principles of nanoparticle design for overcoming biological barriers to drug delivery.

Elvin Blanco, Haifa Shen, Mauro Ferrari (2015)

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

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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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Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date

Daniel Bobo, Kye J. Robinson, Jiaul Islam … (2016)

In this review we provide an up to date snapshot of nanomedicines either currently approved by the US FDA, or in the FDA clinical trials process. We define nanomedicines as therapeutic or imaging agents which comprise a nanoparticle in order to control the biodistribution, enhance the efficacy, or otherwise reduce toxicity of a drug or biologic. We identified 51 FDA-approved nanomedicines that met this definition and 77 products in clinical trials, with ~40% of trials listed in clinicaltrials.gov started in 2014 or 2015. While FDA approved materials are heavily weighted to polymeric, liposomal, and nanocrystal formulations, there is a trend towards the development of more complex materials comprising micelles, protein-based NPs, and also the emergence of a variety of inorganic and metallic particles in clinical trials. We then provide an overview of the different material categories represented in our search, highlighting nanomedicines that have either been recently approved, or are already in clinical trials. We conclude with some comments on future perspectives for nanomedicines, which we expect to include more actively-targeted materials, multi-functional materials ("theranostics") and more complicated materials that blur the boundaries of traditional material categories. A key challenge for researchers, industry, and regulators is how to classify new materials and what additional testing (e.g. safety and toxicity) is required before products become available.

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Journal

Journal ID (nlm-ta): Pharmaceutics

Journal ID (iso-abbrev): Pharmaceutics

Journal ID (publisher-id): pharmaceutics

Title: Pharmaceutics

Publisher: MDPI

ISSN (Electronic): 1999-4923

Publication date (Electronic): 28 November 2020

Publication date Collection: December 2020

Volume: 12

Issue: 12

Electronic Location Identifier: 1160

Affiliations

[1 ]Industrial Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, GR–15771 Athens, Greece; skourtisd@ 123456chem.uoa.gr (D.S.); dimistavrou@ 123456chem.uoa.gr (D.S.); bathanas@ 123456chem.uoa.gr (V.A.)

[2 ]Dyeing, Finishing, Dyestuffs and Advanced Polymers Laboratory, University of West Attica, DIDPE, 250 Thevon Street, GR–12241 Athens, Greece; pgfragouli@ 123456uniwa.gr

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[* ]Correspondence: iatrou@ 123456chem.uoa.gr ; Tel.: +30-210-727-4330

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Dimitrios Skourtis https://orcid.org/0000-0003-2709-6551

Hermis Iatrou https://orcid.org/0000-0001-9358-0769

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Publisher ID: pharmaceutics-12-01160

DOI: 10.3390/pharmaceutics12121160

PMC ID: 7760553

PubMed ID: 33260547

SO-VID: 812ad56f-6aad-42e5-9211-22cf19d388af

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Nanostructured Polymeric, Liposomal and Other Materials to Control the Drug Delivery for Cardiovascular Diseases

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Karger: Cardiovascular System

Most cited references 72

Principles of nanoparticle design for overcoming biological barriers to drug delivery.

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

Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date

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