Science Current Events | Science News | Brightsurf.com
 

Developing a modular, nanoparticle drug delivery system

October 08, 2007

There are two aspects to creating an effective drug: finding a chemical compound that has the desired biological effect and minimal side-effects and then delivering it to the right place in the body for it to do its job.

With the support from a $478,000, five-year CAREER award from the National Science Foundation, Eva Harth is tackling the second part of this problem. She is creating a modular, multi-functional drug delivery system that promises simultaneously to enhance the effectiveness and reduce undesirable side-effects of a number of different drugs.

(NSF's Faculty Early Career Development awards are the agency's most prestigious honor for junior faculty members and are given to individuals judged most likely to become the academic leaders of the 21st century.)

Harth, who is an assistant professor of chemistry at Vanderbilt University, has created a "nanosponge" specially designed to carry large numbers of drug molecules. She has also discovered a "molecular transporter" that, when attached to the nanosponge, carries it and its cargo across biological barriers into specific intracellular compartments, which are very difficult places for most drugs to reach. She has shown that her system can reach another difficult target: the brain. Experiments have shown that it can pass through the brain-blood barrier. In addition, she has: successfully attached a special "targeting unit" that delivers drugs to the surface of tumors in the lungs, brain and spinal cord and even developed a "light kit" for her delivery system - fluorescent tags that researchers can use to monitor where it goes.

Harth has taken a different approach from other researchers working on nanotechnology for drug development. Instead of trying to encapsulate drugs in nanoscale containers, she decided to create a nanoparticle that had a large number of surface sites where drug molecules could be attached. To do so, she adopted a method that uses extensive internal cross-linking to scrunch a long, linear molecule into a sphere about 10 nanometers in diameter, about the size of a protein. Nanoparticles like this are called nanosponges.

"We can really load this up with a large number of drug molecules," she says.

Working with Heidi Hamm, the Earl W. Sutherland Jr. Professor of Pharmacology at Vanderbilt, Harth synthesized a dendritic molecule with the ability to slip through cell membranes and reach the cell nucleus. They figured out how to attach this "transporter" to her nanoparticle and showed that the transporter can pull the nanoparticle after it into cellular compartments. They also demonstrated that the transporter can deliver large molecules - specifically peptides and proteins - into specific sub-cellular locations.

"Peptides and proteins can act as drugs, just like smaller molecules," Harth says. "However, there is not much activity in this area because people haven't had a method for getting them into cells. Now that there is a way to do it, but that may change."

Hamm studies G proteins, arguably the most important signaling molecules in the cell. Scientists think that many diseases, including diabetes and certain forms of pituitary cancer, are caused by malfunctioning G proteins. She and Harth are collaborating on using the transporter to deliver peptides produced by G proteins that disrupt signaling pathways.

"Eva's methods for drug delivery are very novel and versatile and can be adapted to delivery of proteins, peptides, DNA and smaller chemical compounds like most drugs. The breadth of applications makes her technology very powerful," Hamm says.

The chemist is also collaborating with Dennis E. Hallahan, professor of radiation oncology at Vanderbilt, to apply the drug delivery system to fighting cancer. Hallahan's lab had identified a molecule that targets a surface feature on lung carcinomas. Harth took the molecule, improved it, attached it to her nanoparticle and the two of them determined that the combination is capable of delivering drugs to the surface of lung tumors.

She is now working with Hallahan to adapt her delivery system to carry cisplatinum, a traditional chemotherapy agent that is used to treat a number of different kinds of cancer but is highly toxic and has a number of unpleasant side effects.

By delivering the anti-cancer agent directly to the cancerous tissues, Eva's system decreases the adverse effects on other tissues and increases its potency by delivering a higher concentration of the drug directly on the cancer, Hallahan explains.

"The people in my lab have tried at a number of different drug delivery systems and Eva's works the best of those we've looked at," Hallahan says.

Vanderbilt is applying for two patents on the system.

Vanderbilt University


Related Drug Delivery Current Events and Drug Delivery News Articles


Implantable device targets pancreatic cancer
Pancreatic cancer is the third leading cause of cancer deaths in the United States, in part because it is very difficult for chemotherapy drugs to reach the pancreas, which is located deep within the abdomen.

Engineers develop a pill for long-term drug release
Researchers from MIT and Brigham and Women's Hospital have designed a new type of pill that, once swallowed, can attach to the lining of the gastrointestinal tract and slowly release its contents.

Revealing the fluctuations of flexible DNA in 3-D
An international team working at the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) has captured the first high-resolution 3-D images from individual double-helix DNA segments attached at either end to gold nanoparticles. The images detail the flexible structure of the DNA segments, which appear as nanoscale jump ropes.

Nanocage surfaces get 'makeover' in room temperature
Kyoto University researchers have discovered a way of replacing surface ions of copper oxide nanocrystals at ambient conditions -- a feat that will make nanocage production considerably simpler.

IBS Creates a wearable graphene-based biomedical device to monitor and combat diabetes
A scientific team from the Center for Nanoparticle Research at IBS has created a wearable GP-based patch that allows accurate diabetes monitoring and feedback therapy by using human sweat.

Clot-busting drug reduces death risk in hemorrhagic stroke patients
Reporting on the results of a phase III international clinical trial, Johns Hopkins Medicine physicians say use of a cardiac clot-busting drug to treat strokes that cause brain bleeding safely decreased the death rate in patients by 10 percent, compared to a control group receiving saline.

UA College of Pharmacy faculty member develops inhalers to treat lung diseases
Heidi M. Mansour, PhD, assistant professor in the University of Arizona College of Pharmacy, is working to develop advanced dry powder inhalers to treat and prevent pulmonary diseases.

Improvised naloxone nasal sprays lack evidence of absorption and effect
Naloxone hydrochloride is a medication that can reverse the effects of an opioid overdose. First responders (peers, family, police, etc.) may prefer nasal sprays to injectable naloxone, which has led to widespread use of improvised naloxone kits with atomisers for nasal delivery of the drug.

Tiny electronic implants monitor brain injury, then melt away
A new class of small, thin electronic sensors can monitor temperature and pressure within the skull - crucial health parameters after a brain injury or surgery - then melt away when they are no longer needed, eliminating the need for additional surgery to remove the monitors and reducing the risk of infection and hemorrhage.

UNC-Chapel Hill researchers kill drug-resistant lung cancer with 50 times less chemo
The cancer drug paclitaxel just got more effective. For the first time, researchers from the University of North Carolina at Chapel Hill have packaged it in containers derived from a patient's own immune system, protecting the drug from being destroyed by the body's own defenses and bringing the entire payload to the tumor.
More Drug Delivery Current Events and Drug Delivery News Articles

Drug Delivery: Engineering Principles for Drug Therapy (Topics in Chemical Engineering)

Drug Delivery: Engineering Principles for Drug Therapy (Topics in Chemical Engineering)
by W. Mark Saltzman (Author)


Synthetic materials are a tremendous potential resource for treating human disease. For the rational design of many of these biomaterials it is necessary to have an understanding of polymer chemistry and polymer physics. Equally important to those two fields is a quantitative understanding of the principles that govern rates of drug transport, reaction, and disappearance in physiological and pathological situations. This book is a synthesis of these principles, providing a working foundation for those in the field of drug delivery. It covers advanced drug delivery and contemporary biomaterials.


Drug Delivery: Principles and Applications (Wiley Series in Drug Discovery and Development)

Drug Delivery: Principles and Applications (Wiley Series in Drug Discovery and Development)
by Binghe Wang (Author), Longqin Hu (Author), Teruna J. Siahaan (Author)


Following its successful predecessor, this book covers the fundamentals, delivery routes and vehicles, and practical applications of drug delivery. In the 2nd edition, almost all chapters from the previous are retained and updated and several new chapters added to make a more complete resource and reference. • Helps readers understand progress in drug delivery research and applications
• Updates and expands coverage to reflect advances in materials for delivery vehicles, drug delivery approaches, and therapeutics
• Covers recent developments including transdermal and mucosal delivery, lymphatic system delivery, theranostics
• Adds new chapters on nanoparticles, controlled drug release systems, theranostics, protein and peptide drugs, and biologics...

Drug Delivery

Drug Delivery
by Ashim K. Mitra (Author), Deep Kwatra (Author), Aswani Dutt Vadlapudi (Author)


Drug Delivery is the latest and most up-to-date text on drug delivery and offers an excellent working foundation for students and clinicians in health professions and graduate students including nursing, pharmacy, medicine, and dentistry, as well as researchers and scientists. Presenting complex content in an organized and concise format, this accessible text provides a detailed overview of drug delivery systems, routes of drug administration and development of various formulations. This text provides a comprehensive review of the cutting edge research being carried out in this field and a focus on the worldwide research on drug delivery and targeting at the molecular, cellular, and organ levels. KEY TOPICS CNS delivery Gene delivery Ocular delivery World-wide research on drug delivery...

Advanced Drug Delivery

Advanced Drug Delivery
by Ashim Mitra (Author), Chi H. Lee (Author), Kun Cheng (Author)


Provides both fundamentals and new and emerging applications Advanced Drug Delivery brings readers fully up to date with the state of the science, presenting the basics, formulation strategies, and therapeutic applications of advanced drug delivery. The book demonstrates how core concepts of pharmaceutical sciences, chemistry, and molecular biology can be combined and applied in order to spark novel ideas to design and develop advanced drug delivery systems for the treatment of a broad range of human diseases. Advanced Drug Delivery features contributions from an international team of pharmaceutical scientists. Chapters reflect a thorough review and analysis of the literature as well as the authors' firsthand experience developing drug delivery systems. The book is divided into four...

Drug Delivery: Materials Design and Clinical Perspective

Drug Delivery: Materials Design and Clinical Perspective
by Eric Holowka (Author), Sujata K. Bhatia (Author)


Current pharmaceutical and clinical approaches to the treatment of disease suffer from the inherent limitations in the specialization of drugs introduced to physiological systems. The interface of clinical and material sciences has allowed for a broad spectrum of creative approaches with the potential to alleviate these shortcomings. However, the synergy of these disciplines also presents problems in which nascent technology lacks the necessary evaluation within its intended clinical environment. Given the growing potential for materials science to address a number of unanswered therapeutic needs, it remains even more pressing to validate emerging drug delivery technologies in actual clinical environments. Drug Delivery: Materials Design and Clinical Perspective addresses the core...

Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems

Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems
by Loyd V. Allen Jr. PhD (Editor), Nicholas G. Popovich PhD (Editor), Howard C. Ansel PhD (Editor)


Long established as a core text for pharmaceutics courses, this book is the most comprehensive source on pharmaceutical dosage forms and drug delivery systems. Content coincides with the CAPE, APhA, and NAPLEX® competencies. This edition includes updated drug information and has an increased focus on physical pharmacy. Coverage incorporates all new dosage forms on the market as well as those in the current US Pharmacopoeia-National Formulary. Updated photos are included. An "Applying the Principles and Concepts" section at the end of each chapter provides activities for the application of the material. A companion website includes the fully searchable text and a quiz bank with more than 200 questions written in NAPLEX® format.

Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems

Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems
by Loyd Allen (Author)


Succeed in your course with the most comprehensive source on pharmaceutical dosage forms and drug delivery systems available today. Reflecting the CAPE, APhA, and NAPLEX® competencies, this trusted resource covers physical pharmacy, pharmacy practice, pharmaceutics, compounding, and dosage forms and the clinical application of the various dosing forms in patient care. The 10th edition features a dynamic new full color design, new coverage of prescription flavoring, and additional coverage of expiration dates.   See pharmaceutical concepts in action through the two case studies (one pharmaceutical and one clinical) in each dosing forms chapter. Practice applying material using the group and individual activities in Applying the Principles and Concepts sections...

Drug Delivery Across Physiological Barriers

Drug Delivery Across Physiological Barriers
by Silvia Muro (Editor)


For most therapeutics, the targets of action are intracellular and/or require penetration across cellular and tissue layers. The design of strategies capable of controlling the transport of therapeutic agents through these physiological barriers has, hence, become an imperative and yet challenging need in the quest for better therapeutics. This book provides an overview of the current advances in this field from multiple perspectives, including considerations on the biological regulation and natural mechanisms overcoming these barriers, as well as drug delivery strategies facilitating the transport of drugs and their carriers at the tissue, cell, and subcellular levels.

Inhalation Drug Delivery: Techniques and Products

Inhalation Drug Delivery: Techniques and Products
by Paolo Colombo (Editor), Daniela Traini (Editor), Francesca Buttini (Editor)


There has been a rapid evolution in the field of inhalation drug therapy, including new drugs, increased regulation and quality control, and strong pressure from generics. Inhalation Drug Therapy brings together the most current inhalation drug research, as well as practical developments and processes, into one essential guide. Focusing on inhalation products and specific equipment and techniques used in manufacturing and quality control, the book balances research with the industrial aspects of creating the drugs, and features a highly regarded author team with both academic and industry experience.

Nanotechnology in Drug Delivery: Fundamentals, Design, and Applications

Nanotechnology in Drug Delivery: Fundamentals, Design, and Applications
by Saurabh Bhatia (Author)


This important new book provides the fundamental understanding of the peptide and protein drug delivery systems with a special focus on their nanotechnology applications. Addressing an increasing interest in peptide and protein drug delivery systems in both academic and industrial circles worldwide, this book fills the need for a comprehensive review and assessment of conventional and nonconventional routes of administration.

© 2016 BrightSurf.com