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Dynamite comes in Small Packages “Nano Medicines” Dr Steven Mufamadi, PhD (Wits) SAAPI Conference 2016 Nanomedicine What future medical miracles lie ahead? o The next big thing in medicine will comes from something really small? “Nanomedicine is the next disruption in pharmaceutical industry” Nanomedicine What is nanomedicine? o It is the medical application of nanotechnology o Nanomedicine can be used in many fields of medicine - NanoPharmaceutics [Drug Delivery System] - Diagnostics - Vaccine - Biomaterials - Biological Device - Nanorobot - visualization Nanomedicine “Nanotechnology” What is nanotechnology? o Manipulation of materials at the atomic and molecular size level to produce a novel characteristics. o Nanoscale = 1-100nm o The prefix ‘nano’ is derived from the Greek word for dwarf Nanotechnology How small is nano? “In Nanoworld: Size matters” Human Hair ~ 500-100,000 nm Red blood cell ~7 000 nm in diameter ~2 000 nm in height Nanoparticles are comparable in size to organelles such as ribosomes Nanotechnology How small is nano? Nanomedicine “Shape & raw materials” “In Nanoworld: Shape & raw materials also matters” Shape Spheres Discs Cylinders Hollow Tubes & Wires Shape selection o Interactivity o Loading capacity o Transport capabilities o Properties Raw materials [Lipid-based nanoparticles] o Phospholipids [ Biocompatibility] [Safe by FDA, not stable] Raw materials [Polymer-based nanoparticles] o Natural polymers o Synthetic polymers o[Gold nanoparticles] [More stable, but Toxic] Nanomedicine “Surface structure” “In Nanoworld: Surface structure also matters” Functionalizations-Nanoparticles o Transport drugs to specific locations [e.g., Organs, Cells or Tissues] o Targeting ligand [Small molecules, peptide, protein] [Antibodies & carbohydrate] o Surface charge [Positive or negative] o Combination [Lipid vs Polymer] [Safety & stability] Nanomedicine “Drug Delivery System” The roles Nanomedicine will play in the Pharmaceutical Industry Improve oDrug Encapsulation Efficiency, DEE] oDrug Delivery Systems, DDS] Improve o Stability o Solubility o Target delivery o Extending [Half-life] Maximizing oBioavailability o Biodistributions Nanomedicine “Drug Delivery System” The roles Nanomedicine will play in the Pharmaceutical Industry o Point of Care Diagnostics o Point of Care Formulation Monitoring [Drug distribution] [Drug resistant ] Active Molecule [Drugs] [Proof of Concept, PoC] [Point of Care, PoC ] Nanomedicine “Drug Delivery System” The roles Nanomedicine will play in the Pharmaceutical Industry o Reformulation of drugs - Bringing back the “old” drug into new life - Bringing back high toxic drug into new life - Improve Bioavailability & toxicity profiles [Improve patient compliance] FDA approval of Combination Therapy o Abraxane plus gemcitabine [Nanoparticle albumin bound paclitaxel] o Metastatic pancreatic cancer treatment o Patients lived longer, on avarge,1.8 months longer than those treated with gemcitabine alone Nanomedicine “Drug Delivery System” The roles Nanomedicine will play in the Pharmaceutical Industry Programmable Nano-Based Therapeutics [Control release] o Nanoparticle-Activated to release therapeutic in response to a site-specific or due to stimulus or environmental facts Nanoparticle properties [Stimuli‐triggered systems] Nanomedicine “Drug Delivery System” The roles Nanomedicine will play in the Pharmaceutical Industry o Nanomedicine: Bypass BBB barrier Blood Brain Barrier [BBB] Nanomedicine “Drug Delivery System” The roles Nanomedicine will play in the Pharmaceutical Industry o Nanomedicine: Bypass BBB barriers Blood Brain Barrier [BBB] 1-100nm size 1-100nm size Nanomedicine “Drug Delivery System” The roles Nanomedicine will play in the Pharmaceutical Industry o Nanomedicine: Bypass skin barriers Stable High drug distribution High bioavailability [Nanoparticle-Skin layer ] Nanomedicine “Disease/Disorder” Nanomedicine in diseases/disorders o Human Immunodeficiency Virus o o o o (HIV) Tuberculosis (TB) Malaria Cancer Neurodegenerative Diseases Nanomedicine “HIV/AIDS” Nanomedicine in HIV Inexpensive diagnostic devices o Early HIV detection [Window period and/or Latent stage] o Rapid diagnostics [30-60min] o Drug delivery: Macrophages & CD4 cells o Triple-drug combination Lipid nanoparticles containing lopinavir (LPV) ritonavir (RTV), and tenofovir (PMPA) Nanomedicine “Tuberculosis (TB)” Nanomedicine in TB o Inexpensive TB diagnostic devices o Inexpensive drug monitoring or drug resistance devices o Slow drug release -TB drugs incorporated into nanoparticles - Bypass daily dosage into every 7-10 days [Increase patient compliance] Nanomedicine “Malaria parasites” Nanomedicine in Malaria parasites o Repellent [e.g SI & Silver Nanoparticles] [Nanoparticles in paint, mosquito nets, clothes e.g School & military uniform] o Inexpensive Malaria diagnostic devices o Reformulating antimalarials towards a single dose cure and/or maximizing bioavailability [e.g. Quinine] Nanomedicine “Neurodegenerative disease” Nanomedicine in Neurodegenerative diseases Parkinson & Alzheimer's diseases o Getting drugs to crossing the BBB [e.g Galantamine & Levodopa] o Target delivery [Specific brain cells] o Implantable: Nanodevice [Nanoscaffold] o Prolonged drug release [Chronic conditions] Nanomedicine “Cancer” Nanomedicine in cancer Theragnostics [Therapeutic and Diagnostic agents] o Real-time bio‐distribution o Real-time target accumulation Nanomedicine “Therapeutics area” Nanomedicine global sales by Therapeutic area Nanomedicine Big Pharma in Nanomedicine? Pfizer signed a deal with BIND Therapeutics Inc (BIND) . Accurins [Polymeric nanoparticles] o o Highly selective targeted and programmable nano-based therapeutics o Oncology, Inflammatory diseases and cardiovascular disorders Merck signed a deal with NanoBio Corporation o Nanoemulsion (NE) adjuvant technology o Intranasal respiratory syncytial virus (RSV) and influenza vaccine Gilead Sciences [AmBisome®] Novartis [Neoral®] Abraxis Bioscience [Abraxane®] Roche [Forovase®] GSK[Exosurf®] AstraZeneca [Diprivan®] FDA‐approved and marketed nanopharmaceutical products Nanorobots “Future” o A nanorobot is a tiny machine designed to perform a specific task at nanoscale dimensions o Drug delivery robots o Correct DNA or a deficiency o Cell repair Nanorobots o Break up blood clots o Break even kidney stones Nanorobots “Future” Replacing neurons with nanorobots [Computerization of the brain] Full-functional nanorobots capable of self-replicating & synthesizing any Organic structure Artificial red blood cell o Capable to deliver 236 times more oxygen to the tissues per unit “Treatment of Anemia” Nanomedicine Risks & Toxicology Health Environmental Nanomedicine Challenges Dr Richard Smalley “Quote” Dr. Richard Smalley once said; “Human health has always been determined on nanometer scale; this is where the structure and properties of the machines of life work in every one of the cells in every living thing. Therefore, the practical impact of nanosciences on human health will be huge” Dr Angela Hullmmann “Quote” Dr. Angela Hullmann once said; “Nanotechnology will have a positive impact on economic development only if it provides new solutions and does not create new problems” Reference 1. 2. 3. 4. 5. 6. 7. 8. 9. "Nanomedicine." Wickepedia. N.p., n.d. Web. 18 Apr 2010. <http://en.wikipedia.org /wiki/Nanomedicine Ventola CL. The Nanomedicine Revolution Part 1: Emerging Concepts.P T. 2012 Sep; 37(9): 512-7 Mansour et al., Design and development of approved nanopharmaceutical products, Handbook of Clinical Nanomedicine, 2015 Fact Sheet: Nanotechnology. FDA Guidance, Compliance, & Regulatory Information. Available at: www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/ucm30 0914.htm. Accessed June 7, 2012. Park K. Nanotechnology: What it can do for drug delivery. J Control Release. 2007;120:1–7 Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano,2009;3:16–20 Freeling et al. Anti-HIV drug-combination nanoparticles enhance plasma drug exposure duration as well as triple-drug combination levels in cells within lymph nodes and blood in primates. AIDS Res Huma Retroviruses, 2015;31(1): 107-14 Hood et alVreeland WN, DeVoe DL. Microfluidic remote loading for rapid single-step liposomal drug preparation. Lab Chip, 2014;14(17):3359-67. Spinelli., Albumin bound formulation of paclitaxel in the treatment of breast cancer. International J Nanomedicine, 4:99. Office: 012 7563905 Mobile: 0814350353 [email protected] www.nabioconsulting.co.za