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Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials.
Dendrimers are highly ordered, branched polymeric molecules. Synonymous terms for dendrimer include arborols and cascade molecules. Typically, dendrimers are symmetric about the core, and often adopt a spherical three-dimensional morphology. The word dendron is also encountered frequently. A dendron usually contains a single chemically addressable group called the focal point or core. The difference between dendrons and dendrimers is illustrated in the top figure, but the terms are typically encountered interchangeably.
Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. This means of delivery is largely founded on nanomedicine, which plans to employ nanoparticle-mediated drug delivery in order to combat the downfalls of conventional drug delivery. These nanoparticles would be loaded with drugs and targeted to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. The conventional drug delivery system is the absorption of the drug across a biological membrane, whereas the targeted release system releases the drug in a dosage form. The advantages to the targeted release system is the reduction in the frequency of the dosages taken by the patient, having a more uniform effect of the drug, reduction of drug side-effects, and reduced fluctuation in circulating drug levels. The disadvantage of the system is high cost, which makes productivity more difficult, and the reduced ability to adjust the dosages.
Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata, a tree native to China used in traditional Chinese medicine. It has been used clinically more recently in China for the treatment of gastrointestinal tumors. CPT showed anticancer activity in preliminary clinical trials, especially against breast, ovarian, colon, lung, and stomach cancers. However, it has low solubility and adverse effects have been reported when used therapeutically, so synthetic and medicinal chemists have developed numerous syntheses of camptothecin and various derivatives to increase the benefits of the chemical, with good results. Four CPT analogues have been approved and are used in cancer chemotherapy today, topotecan, irinotecan, belotecan, and trastuzumab deruxtecan. Camptothecin has also been found in other plants including Chonemorpha fragrans.
Insert Therapeutics, Inc., now Calando Pharmaceuticals, Inc., is a medical research company that uses nanobiotechnology specializing in therapeutic agents that are conjugated, to facilitate and enhance drug delivery. The small company was founded in 2000, is located in Pasadena, California, and is owned by Arrowhead Research Corporation.
Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for adults and children with rare and difficult-to-treat cancers. The company is headquartered in Austin, Texas, United States.
N-(2-Hydroxypropyl)methacrylamide or HPMA is the monomer used to make the polymer poly(N-(2-hydroxypropyl)methacrylamide).
Polymer-drug conjugates are nano-medicine products under development for cancer diagnosis and treatment. There are more than 10 anticancer conjugates in clinical development. Polymer-drug conjugates are drug molecules held in polymer molecules, which act as the delivery system for the drug. Polymer drugs have passed multidrug resistance (MDR) testing and hence may become a viable treatment for endocrine-related cancers. A cocktail of pendant drugs could be delivered by water-soluble polymer platforms. The physical and chemical properties of the polymers used in polymer-drug conjugates are specially synthesized to flow through the kidneys and liver without being filtered out, allowing the drugs to be used more effectively. Traditional polymers used in polymer-drug conjugates can be degraded through enzymatic activity and acidity. Polymers are now being synthesized to be sensitive to specific enzymes that are apparent in diseased tissue. The drugs remain attached to the polymer and are not activated until the enzymes associated with the diseased tissue are present. This process significantly minimizes damage to healthy tissue.
Mark E. Davis is the Warren and Katherine Schlinger Professor of Chemical Engineering at the California Institute of Technology. He is a member of the City of Hope National Medical Center. He earned his B.S., M.S., and Ph.D. in Chemical Engineering all from the University of Kentucky. His lab focuses on the synthesis of materials for catalysis and biocompatible materials for drug delivery.
Directed enzyme prodrug therapy (DEPT) uses enzymes artificially introduced into the body to convert prodrugs, which have no or poor biologically activity, to the active form in the desired location within the body. Many chemotherapy drugs for cancer lack tumour specificity and the doses required to reach therapeutic levels in the tumour are often toxic to other tissues. DEPT strategies are an experimental method of reducing the systemic toxicity of a drug, by achieving high levels of the active drug only at the desired site. This article describes the variations of DEPT technology.
Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood–brain barrier (BBB) using nanoparticles. These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors. Part of the difficulty in finding cures for these central nervous system (CNS) disorders is that there is yet no truly efficient delivery method for drugs to cross the BBB. Antibiotics, antineoplastic agents, and a variety of CNS-active drugs, especially neuropeptides, are a few examples of molecules that cannot pass the BBB alone. With the aid of nanoparticle delivery systems, however, studies have shown that some drugs can now cross the BBB, and even exhibit lower toxicity and decrease adverse effects throughout the body. Toxicity is an important concept for pharmacology because high toxicity levels in the body could be detrimental to the patient by affecting other organs and disrupting their function. Further, the BBB is not the only physiological barrier for drug delivery to the brain. Other biological factors influence how drugs are transported throughout the body and how they target specific locations for action. Some of these pathophysiological factors include blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered gene expression and protein synthesis. Though there exist many obstacles that make developing a robust delivery system difficult, nanoparticles provide a promising mechanism for drug transport to the CNS.
Nektar Therapeutics (Nektar) is an American biopharmaceutical company. The company was founded in 1990 and is based in San Francisco, California. The company develops new drug candidates by applying its proprietary PEGylation and advanced polymer conjugate technologies to modify chemical structure of substances. It is a technology supplier to a number of pharmaceutical companies including Affymax, Amgen, Merck, Pfizer and UCB Pharma, etc. The company developed the world's first inhalable non-injectable insulin, Exubera, which was awarded as the bronze award by Wall Street Journal for its technological breakthrough.
Gold nanoparticles in chemotherapy and radiotherapy is the use of colloidal gold in therapeutic treatments, often for cancer or arthritis. Gold nanoparticle technology shows promise in the advancement of cancer treatments. Some of the properties that gold nanoparticles possess, such as small size, non-toxicity and non-immunogenicity make these molecules useful candidates for targeted drug delivery systems. With tumor-targeting delivery vectors becoming smaller, the ability to by-pass the natural barriers and obstacles of the body becomes more probable. To increase specificity and likelihood of drug delivery, tumor specific ligands may be grafted onto the particles along with the chemotherapeutic drug molecules, to allow these molecules to circulate throughout the tumor without being redistributed into the body.
Nanosponges are a type of nanoparticle, often a synthesized carbon-containing polymer. They are porous in structure, pores being about 1–2 nanometers in size, and can therefore be targeted to absorb small amounts of matter or toxin. Nanosponges are often used in medicine as targeted drug delivery systems, detoxification methods, or as a way of damage control after an injury. They can also be used in environmental applications to clean up ecosystems by performing tasks like purifying water or metal deposits. Their small size allows them to move quickly through substances, like water or blood, efficiently finding and attacking unwanted matter. Nanosponges are often synthetically manufactured but oftentimes include natural materials to improve their efficiency when injected into the body. Nanosponges are superior to microsponges in application as the smaller size allows less disruption into the system in which it is implemented therefore imposing less risk of failed or detrimental effects. The prefix "nano" implies that items of this size are measured on a scale of meters.
Andreas Bernkop-Schnürch is an Austrian pharmaceutical technologist, scientist, pharmacist, entrepreneur, inventor and professor at the Institute of Pharmacy, University of Innsbruck. His research centers on the areas of pharmaceutical sciences, drug delivery, controlled release, bionanotechnology and polymer engineering. He is the inventor of various technologies such as thiolated polymers for that he coined the name thiomers in 2000 and phosphatase triggered charge converting nanoparticles for mucosal drug delivery. From 2016 to 2018 he served as a member of the Scientific Committee of the Innovative Medicines Initiative (IMI) of the European Union in Brussels giving advice on scientific priorities to be included in the Strategic Research Agenda for Horizon 2020. Since 2014 he is on the scientific advisory board of the Nicotine Science Center, Denmark. Andreas Bernkop-Schnürch is the founder of Mucobiomer Biotechnologische Forschungs- und Entwicklungs GmbH, Thiomatrix Forschungs- und Beratungs GmbH and Green River Polymers Forschungs und Entwicklungs GmbH. He is listed as a Highly Cited Researcher of the Institute of Scientific Information. As of December 2022 his publications have been cited 30,000 times and his H-index is 86
Nanoparticle drug delivery systems are engineered technologies that use nanoparticles for the targeted delivery and controlled release of therapeutic agents. The modern form of a drug delivery system should minimize side-effects and reduce both dosage and dosage frequency. Recently, nanoparticles have aroused attention due to their potential application for effective drug delivery.
Hamid Ghandehari is an Iranian-American drug delivery research scientist, and a professor in the Departments of Pharmaceutics and Pharmaceutical Chemistry and Biomedical Engineering at the University of Utah. His research is focused in recombinant polymers for drug and gene delivery, nanotoxicology of dendritic and inorganic constructs, water-soluble polymers for targeted delivery and poly(amidoamine) dendrimers for oral delivery.
Cytokines are polypeptides or glycoproteins that help immune cells communicate to each other to induce proliferation, activation, differentiation, and inflammatory or anti-inflammatory signals in various cell types. Studies utilizing cytokines for antitumor therapies has increased significantly since 2000, and different cytokines provide unique antitumor activities. Cytokines hinder tumor cell development mostly through antiproliferative or proapoptotic pathways but can also interrupt development indirectly by eliciting immune cells to have cytotoxic effects against tumor cells. Even though there are FDA-approved cytokine therapies, there are two main challenges associated with cytokine delivery. The first is that cytokines have a short half-life, so frequent administration of high doses is required for therapeutic effect. The second is that systemic toxicity could occur if the cytokines delivered cause an intense immune response, known as a cytokine storm.
Dextran drug delivery systems involve the use of the natural glucose polymer dextran in applications as a prodrug, nanoparticle, microsphere, micelle, and hydrogel drug carrier in the field of targeted and controlled drug delivery. According to several in vitro and animal research studies, dextran carriers reduce off-site toxicity and improve local drug concentration at the target tissue site. This technology has significant implications as a potential strategy for delivering therapeutics to treat cancer, cardiovascular diseases, pulmonary diseases, bone diseases, liver diseases, colonic diseases, infections, and HIV.
Reduction-sensitive nanoparticles (RSNP) consist of nanocarriers that are chemically responsive to reduction. Drug delivery systems using RSNP can be loaded with different drugs that are designed to be released within a concentrated reducing environment, such as the tumor-targeted microenvironment. Reduction-Sensitive Nanoparticles provide an efficient method of targeted drug delivery for the improved controlled release of medication within localized areas of the body.
References
- ↑ Weiss GJ, Chao J, Neidhart JD, Ramanathan RK, Bassett D, Neidhart JA, Choi CH, Chow W, Chung V, Forman SJ, Garmey E, Hwang J, Kalinoski DL, Koczywas M, Longmate J, Melton RJ, Morgan R, Oliver J, Peterkin JJ, Ryan JL, Schluep T, Synold TW, Twardowski P, Davis ME, Yen Y (2013). "First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies". Invest. New Drugs. 31 (4): 986–1000. doi:10.1007/s10637-012-9921-8. PMC 3774600 . PMID 23397498.
- ↑ "Survival". thirteen.org.