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Overcoming Physiological Barriers to Nanoparticle Delivery-Are We There Yet?

ABSTRACT: The exploitation of nanosized materials for the delivery of therapeutic agents is already a clinical reality and still holds unrealized potential for the treatment of a variety of diseases. This review discusses physiological barriers a nanocarrier must overcome in order to reach its target, with an emphasis on cancer nanomedicine. Stages of delivery include residence in the blood stream, passive accumulation by virtue of the enhanced permeability and retention effect, diffusion within the tumor lesion, cellular uptake, and arrival at the site of action. We also briefly outline strategies for engineering nanoparticles to more efficiently overcome these challenges: Increasing circulation half-life by shielding with hydrophilic polymers, such as PEG, the limitations of PEG and potential alternatives, targeting and controlled activation approaches. Future developments in these areas will allow us to harness the full potential of nanomedicine.

SUBMITTER: Thomas OS

PROVIDER: S-EPMC6928054 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Overcoming Physiological Barriers to Nanoparticle Delivery-Are We There Yet?

Thomas Oliver S OS Weber Wilfried W

Frontiers in bioengineering and biotechnology 20191217

The exploitation of nanosized materials for the delivery of therapeutic agents is already a clinical reality and still holds unrealized potential for the treatment of a variety of diseases. This review discusses physiological barriers a nanocarrier must overcome in order to reach its target, with an emphasis on cancer nanomedicine. Stages of delivery include residence in the blood stream, passive accumulation by virtue of the enhanced permeability and retention effect, diffusion within the tumor ...[more]

PMID: 31921819

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Project description:Negatively charged tissues are ubiquitous in the human body and are associated with a number of common diseases yet remain an outstanding challenge for targeted drug delivery. While the anionic proteoglycans are critical for tissue structure and function, they make tissue matrix dense, conferring a high negative fixed charge density (FCD) that makes drug penetration through the tissue deep zones and drug delivery to resident cells extremely challenging. The high negative FCD of these tissues is now being utilized by taking advantage of electrostatic interactions to create positively charged multi-stage delivery methods that can sequentially penetrate through the full thickness of tissues, create a drug depot and target cells. After decades of work on attempting delivery using strong binding interactions, significant advances have recently been made using weak and reversible electrostatic interactions, a characteristic now considered essential to drug penetration and retention in negatively charged tissues. Here we discuss these advances using examples of negatively charged tissues (cartilage, meniscus, tendons and ligaments, nucleus pulposus, vitreous of eye, mucin, skin), and delve into how each of their structures, tissue matrix compositions and high negative FCDs create barriers to drug entry and explore how charge interactions are being used to overcome these barriers. We review work on tissue targeting cationic peptide and protein-based drug delivery, compare and contrast drug delivery designs, and also present examples of technologies that are entering clinical trials. We also present strategies on further enhancing drug retention within diseased tissues of lower FCD by using synergistic effects of short-range binding interactions like hydrophobic and H-bonds that stabilize long-range charge interactions. As electrostatic interactions are incorporated into design of drug delivery materials and used as a strategy to create properties that are reversible, tunable and dynamic, bio-electroceuticals are becoming an exciting new direction of research and clinical work.

Dataset Information

Overcoming Physiological Barriers to Nanoparticle Delivery-Are We There Yet?

Publications

Overcoming Physiological Barriers to Nanoparticle Delivery-Are We There Yet?

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