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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.
The enhanced permeability and retention (EPR) effect is a controversial concept by which molecules of certain sizes tend to accumulate in tumor tissue much more than they do in normal tissues. The general explanation that is given for this phenomenon is that,in order for tumor cells to grow quickly,they must stimulate the production of blood vessels. VEGF and other growth factors are involved in cancer angiogenesis. Tumor cell aggregates as small as 150–200 μm,start to become dependent on blood supply carried out by neovasculature for their nutritional and oxygen supply. These newly formed tumor vessels are usually abnormal in form and architecture. They are poorly aligned defective endothelial cells with wide fenestrations,lacking a smooth muscle layer,or innervation with a wider lumen,and impaired functional receptors for angiotensin II. Furthermore,tumor tissues usually lack effective lymphatic drainage. All of these factors lead to abnormal molecular and fluid transport dynamics,especially for macromolecular drugs. This phenomenon is referred to as the "enhanced permeability and retention (EPR) effect" of macromolecules and lipids in solid tumors. The EPR effect is further enhanced by many pathophysiological factors involved in enhancement of the extravasation of macromolecules in solid tumor tissues. For instance,bradykinin,nitric oxide / peroxynitrite,prostaglandins,vascular permeability factor,tumor necrosis factor and others. One factor that leads to the increased retention is the lack of lymphatics around the tumor region which would filter out such particles under normal conditions.
A drug carrier or drug vehicle is a substrate used in the process of drug delivery which serves to improve the selectivity,effectiveness,and/or safety of drug administration. Drug carriers are primarily used to control the release of drugs into systemic circulation. This can be accomplished either by slow release of a particular drug over a long period of time or by triggered release at the drug's target by some stimulus,such as changes in pH,application of heat,and activation by light. Drug carriers are also used to improve the pharmacokinetic properties,specifically the bioavailability,of many drugs with poor water solubility and/or membrane permeability.
Drug delivery refers to approaches,formulations,manufacturing techniques,storage systems,and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to drug preparation,route of administration,site-specific targeting,metabolism,and toxicity are used to optimize efficacy and safety,and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients,drug carriers,and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example,several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.
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.
Poloxamers are nonionic triblock copolymers composed of a central hydrophobic chain of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene. The word poloxamer was coined by BASF inventor,Irving Schmolka,who received the patent for these materials in 1973. Poloxamers are also known by the trade names Pluronic,Kolliphor, and Synperonic.
A nanocarrier is nanomaterial being used as a transport module for another substance,such as a drug. Commonly used nanocarriers include micelles,polymers,carbon-based materials,liposomes and other substances. Nanocarriers are currently being studied for their use in drug delivery and their unique characteristics demonstrate potential use in chemotherapy. This class of materials was first reported by a team of researchers of University of Évora,Alentejo in early 1960's,and grew exponentially in relevance since then.
Molly S. Shoichet,is a Canadian science professor,specializing in chemistry,biomaterials and biomedical engineering. She was Ontario's first Chief Scientist. Shoichet is a biomedical engineer known for her work in tissue engineering,and is the only person to be a fellow of the three National Academies in Canada.
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.
Ijeoma Uchegbu is a Nigerian-British Professor of Pharmacy at University College London where she held the position of Pro-Vice Provost for Africa and the Middle East. She is the Chief Scientific Officer of Nanomerics,a pharmaceutical nanotechnology company specialising in drug delivery solutions for poorly water-soluble drugs,nucleic acids and peptides. She is also a Governor of the Wellcome,a large biomedical research charity. Apart from her highly cited scientific research in Pharmaceutical Nanoscience,Uchegbu is also known for her work in science public engagement and equality and diversity in Science,Technology,Engineering and Mathematics (STEM).
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.
Helen M. Burt is a British-Canadian pharmaceutical scientist who is the Angiotech Professor of Drug Delivery at the University of British Columbia. She serves as Associate Vice President of Research and Innovation at UBC. Her research considers novel therapeutics based on nanotechnology,including drug delivery systems for the treatment of bladder cancer and coronary artery disease.
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.
Conventional drug delivery is limited by the inability to control dosing,target specific sites,and achieve targeted permeability. Traditional methods of delivering therapeutics to the body experience challenges in achieving and maintaining maximum therapeutic effect while avoiding the effects of drug toxicity. Many drugs that are delivered orally or parenterally do not include mechanisms for sustained release,and as a result they require higher and more frequent dosing to achieve any therapeutic effect for the patient. As a result,the field of drug delivery systems developed into a large focus area for pharmaceutical research to address these limitations and improve quality of care for patients. Within the broad field of drug delivery,the development of stimuli-responsive drug delivery systems has created the ability to tune drug delivery systems to achieve more controlled dosing and targeted specificity based on material response to exogenous and endogenous stimuli.
Pullulan bioconjugates are systems that use pullulan as a scaffold to attach biological materials to,such as drugs. These systems can be used to enhance the delivery of drugs to specific environments or the mechanism of delivery. These systems can be used in order to deliver drugs in response to stimuli,create a more controlled and sustained release,and provide a more targeted delivery of certain drugs.
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.
Protein nanotechnology is a burgeoning field of research that integrates the diverse physicochemical properties of proteins with nanoscale technology. This field assimilated into pharmaceutical research to give rise to a new classification of nanoparticles termed protein nanoparticles (PNPs). PNPs garnered significant interest due to their favorable pharmacokinetic properties such as high biocompatibility,biodegradability,and low toxicity Together,these characteristics have the potential to overcome the challenges encountered with synthetic NPs drug delivery strategies. These existing challenges including low bioavailability,a slow excretion rate,high toxicity,and a costly manufacturing process,will open the door to considerable therapeutic advancements within oncology,theranostics,and clinical translational research.
Alexander Viktorovich Kabanov,is a Russian and American chemist,an educator,an entrepreneur,and a researcher in the fields of drug delivery and nanomedicine.
References
- ↑ Kalvapalle, Rahul (July 5, 2019). "Christine Allen appointed U of T's first associate vice-president and vice-provost, strategic initiatives". U of T News. Retrieved September 1, 2019.
- ↑ "Christine Allen Women enabling science to reach the people who need it". Johnson & Johnson Innovation Labs. Archived from the original on 1 November 2018. Retrieved 30 July 2018.
- 1 2 3 "Christine Allen". Controlled Release Society. Retrieved 30 July 2018.[ permanent dead link ]
- ↑ Government of Canada, Natural Sciences and Engineering Research Council of Canada (2018-05-31). "NSERC - Christine Allen". Natural Sciences and Engineering Research Council of Canada (NSERC). Retrieved 2022-08-01.
- 1 2 Houdaihed, L; Evans, JC; Allen, C (2017). "Overcoming the Road Blocks: Advancement of Block Copolymer Micelles for Cancer Therapy in the Clinic". Mol. Pharm. 14 (8): 2503–2517. doi:10.1021/acs.molpharmaceut.7b00188. PMID 28481116.
- 1 2 Her, S; Jaffray, DA; Allen, C (2017). "Gold nanoparticles for applications in cancer radiotherapy: Mechanisms and recent advancements". Adv Drug Deliv Rev. 109: 84–101. doi:10.1016/j.addr.2015.12.012. PMID 26712711. S2CID 4639841.
- ↑ Kalvapalle, Rahul (September 20, 2019). "10 U of T researchers named fellows of the Canadian Academy of Health Sciences". U of T News. Retrieved October 4, 2019.
- ↑ Dou, Yannan; Zheng, Jinzi; Foltz, Warren; Weersink, Robert; Chaudary, Naz; Jaffray, David; Allen, Christine (25 September 2011). "Heat-activated thermosensitive liposomal cisplatin (HTLC) results in effective growth delay of cervical carcinoma in mice". Journal of Controlled Release. 178 (23): 69–78. doi:10.1016/j.jconrel.2014.01.009. PMID 24440663.
- ↑ Dunn, Michael; Zheng, Jinzi; Rosenblat, Joshua; Jaffray, David; Allen, Christine (25 September 2011). "APN/CD13-targeting as a strategy to alter the tumor accumulation of liposomes". Journal of Controlled Release. 154 (3): 298–305. doi:10.1016/j.jconrel.2011.05.022. PMID 21640146.