NIH VideoCast - Biomedical Engineering: Electrostatic Assembly of Targeted Delivery Agents

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Biomedical Engineering: Electrostatic Assembly of Targeted Delivery Agents

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Air date:	Tuesday, February 8, 2022, 11:00:00 AM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 295 (210 Live, 85 On-demand)
Category:	Special
Runtime:	00:59:05
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Biomedical Engineering Scientific Interest Group Electrostatic assembly can be used to engineer coatings that yield release of different drugs, DNA or protein, resulting in highly tunable multi-agent delivery nanolayered release systems for tissue engineering, biomedical devices, and wound healing applications. Depending on the nature of the LbL assembly, we can generate thin films that rapidly release proteins or peptides within minutes for rapid hemostasis to stop bleeding in soldiers on the battlefield, or release growth factors or other proteins that help to regenerate bone in defects where bone may no longer grow. The manipulation of charge to target other tissues, such as cartilage, is an important means of addressing delivery to dense avascular tissues. For example, we have generated unimolecular charged systems that can be precisely tuned to achieve deep penetration into cartilage to enable extended release treatments for cartilage regeneration. Furthermore, we have developed a modular nanoparticle approach using liposomal core particles and layering them with an electrostatic layer-by-layer (LBL) process in a simple and elegant method of constructing highly tailored ultrathin polymer coatings. The resulting LbL nanoparticles (LbL NPs) have negatively charged outer layers that present polyelectrolytes such as dextran sulfate or hyaluronic acid in a hydrated brush arrangement that enables hydration, steric repulsion, colloidal and serum stability, and specific or non-specific targeting. We have demonstrated that these particles have long systemic plasma blood half-lives and good tumor accumulation over time, and demonstrate efficacy in advanced breast and lung cancer models in which siRNA targets have been delivered with chemotherapy drug in the same nanoparticle system. Ongoing work includes addressing barriers to transport of these nanoparticles relevant to tumor or other tissue penetration, and will be discussed, including new work involving the understanding of these trafficking patterns and a means to leverage them toward the delivery of cytokines for activation of the immune system against ovarian cancer, a cancer which has not previously benefitted from immunotherapeutic approaches. In vitro and in vivo results will be discussed, as well as release mechanisms, toxicity studies and clinical outlook for these targeted systems. Ongoing work includes examination of how these LbL NP systems might be adapted to enhance delivery across the blood-brain barrier for glioblastoma, or modified to enhance tumor accumulation and penetration. These and other uses of controlled polyelectrolytes and their complexes for delivery within tissues and across barriers will be addressed. For more information go to https://oir.nih.gov/sigs/biomedical-engineering-scientific-interest-group

NLM Title:	Electrostatic assembly of targeted delivery agents / Paula Hammond.
Author:	Hammond, Paula T. National Institutes of Health (U.S.). Biomedical Engineering Scientific Interest Group,
Publisher:
Abstract:	(CIT): Electrostatic assembly can be used to engineer coatings that yield release of different drugs, DNA or protein, resulting in highly tunable multi-agent delivery nanolayered release systems for tissue engineering, biomedical devices, and wound healing applications. Depending on the nature of the LbL assembly, we can generate thin films that rapidly release proteins or peptides within minutes for rapid hemostasis to stop bleeding in soldiers on the battlefield, or release growth factors or other proteins that help to regenerate bone in defects where bone may no longer grow. The manipulation of charge to target other tissues, such as cartilage, is an important means of addressing delivery to dense avascular tissues. For example, we have generated unimolecular charged systems that can be precisely tuned to achieve deep penetration into cartilage to enable extended release treatments for cartilage regeneration. Furthermore, we have developed a modular nanoparticle approach using liposomal core particles and layering them with an electrostatic layer-by-layer (LBL) process in a simple and elegant method of constructing highly tailored ultrathin polymer coatings. The resulting LbL nanoparticles (LbL NPs) have negatively charged outer layers that present polyelectrolytes such as dextran sulfate or hyaluronic acid in a hydrated brush arrangement that enables hydration, steric repulsion, colloidal and serum stability, and specific or non-specific targeting. We have demonstrated that these particles have long systemic plasma blood half-lives and good tumor accumulation over time, and demonstrate efficacy in advanced breast and lung cancer models in which siRNA targets have been delivered with chemotherapy drug in the same nanoparticle system. Ongoing work includes addressing barriers to transport of these nanoparticles relevant to tumor or other tissue penetration, and will be discussed, including new work involving the understanding of these trafficking patterns and a means to leverage them toward the delivery of cytokines for activation of the immune system against ovarian cancer, a cancer which has not previously benefitted from immunotherapeutic approaches. In vitro and in vivo results will be discussed, as well as release mechanisms, toxicity studies and clinical outlook for these targeted systems. Ongoing work includes examination of how these LbL NP systems might be adapted to enhance delivery across the blood-brain barrier for glioblastoma, or modified to enhance tumor accumulation and penetration. These and other uses of controlled polyelectrolytes and their complexes for delivery within tissues and across barriers will be addressed.
Subjects:	Drug Carriers--chemistry Drug Delivery Systems--methods Nanoparticles--chemistry Neoplasms--drug therapy Static Electricity
Publication Types:	Lecture Webcast

NLM Classification:	QV 785
NLM ID:	9918351571106676
CIT Live ID:	44671
Permanent link:	https://videocast.nih.gov/watch=44671

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