Nano technology and its releavance to drug designing 08072013

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  • 1. Nanotechnology and its relevance to Drug Designing K V GOPINATH M Pharm PhD,CPhT Tirumala Tirupati Devasthanams TIRUPATI e-mail:gopinath.karnam@gmail.com
  • 2. NANOTECHNOLOGY - DEFİNİTİON  Nanotechnology is the term derived from the Greek word “nano” meaning “dwarf”  Applies the principles in various sciences at a atomic , molecular or submicron level  Dimension range: 0.1 – 100 nm (10-1000 nm for pharmaceutical nanoparticles)  Definition: “Research and technology development at the atomic, molecular or macromolecular levels, in the length scale of approximately 1-100 nanometer range, to provide a fundamental understanding of phenomena and materials at the nano scale, and to create and use structures, devices and systems that have novel properties and functions because of their small and/or intermediate size”.
  • 3. Advantages of Nanotechnology  Methods of preparation simple and easy to scale up  Nano scale components have very high surface areas  Stable and easily freeze-dried  Successful tissue targeting of many drugs (antibiotics, cytostatics, peptides and proteins, nucleic acids etc.)  Protection of drugs against chemical and enzymatic degradation  Reduction of side effects of some active drugs
  • 4. Advantages of Nanotechnology  Mucosal delivery of high molecular weight substances, such as peptides, proteins, oligonucleotides and plasmids  Increased solubility and dissolution rate of poorly soluble substances due to nanosizing improvement of drug bioavailability  New functions arising from nanosizing, such as improved solubility, targetability, and adhesion to tissues  Bionanomaterials:1) Biological materials utilized in nanotechnology - Proteins, enzymes, DNA, RNA, peptides 2) Synthetic nano materials in biomedical applications - Polymers, porous silicon, carbon nanotubes
  • 5. Nanoscale Processes and Fabrication Top-down Approaches Bottom-up Approaches Optical and x-ray lithography Layer-by-layer self assembly E-beam and ion-beam lithography Molecular self assembly Scanning probe lithography Direct assembly Atomic force microscopic lithography Coating and growth Material removal and deposition (Chemical, mechanical, or ultrasonic) Colloidal aggregation Printing and imprinting
  • 6. Equipments for Nanoparticles         Homogenizer Ultra Sonicator Mills Spray Milling Supercritical Fluid Technology Electro spray Ultracentrifugation Nano filtration
  • 7. Schematic representation of Nanosphere Formation –Method 1 2 hours Stirring 1000 rpm Ethyl acetate + PLGA Passed through 0.2 µm filter Add organic to aqueous Aqueous PVA-Chitosan NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 Water NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 Stirring 2 hours NH2 NH2 NH2 NH2 NH2 NH2 Water bath, 40 oCNH NH2 NH2 2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 NH2 Passed through 0.2 µm filter NH2 NH2 NH2 NH2 NH2 2 hours Stirring 1000 rpm NH2 NH2 Mixing 3 hours Stirring 1000 rpm NH2 NH2 Homogenize 10 min 13,500 rpm
  • 8. Polymerization method
  • 9. Different Methods to Prepare Nanospheres and Nanocapsules Polymer Method based on physico-chemical properties of polymer solutions Phase Non solvent gelation Salting-out calcium tripolyphosphates (polymer soluble (polymer soluble in water) in organic solvent) Nanocapsules Nanospheres Nanospheres Alginate nanospheres Chitosan nanospheres
  • 10. microencapsulation techniques-Nanospheres & Nanocapsules Polymer Emulsification Simple emulsion (W/O) (Water soluble) Simple emulsion (O/W) Double emulsion (W/O/W) (polymer soluble in organic solvent) (polymer soluble in organic solvent) Gelation precipitation Solvent evaporation Polymer Polymer precipitation Solvent extraction İnverse salting out Solvent evaporation
  • 11. Nanotechnology Applications Medicine - Cancer treatment - Bone treatment Drug delivery Appetite control Drug development Medical tools Diagnostic tests Imaging Consumer Goods Foods and beverages −Advanced packaging materials, sensors, and labon-chips for food quality testing Appliances and textiles −Stain proof, water proof and wrinkle free textiles Household and cosmetics − Self-cleaning and scratch free products, paints, and better cosmetics
  • 12. Nanotechnology Applications  Medical Nanotechnology or Nano medicine  Nano medicine is the application of nanotechnology in medicine, including to cure diseases and repair damaged tissues such as bone, muscle, and nerve and its monitoring  Key Goals for Nano medicine: −To develop cure for traditionally incurable diseases (e.g. cancer) through the utilization of nanotechnology −To provide more effective cure with fewer side effects by means of targeted drug delivery systems
  • 13. Nanotechnology in Health Care Detection and Diagnosis  Nanotechnology offers tools  Lab on chips help detection and diagnosis of diseases more efficiently and techniques for more effective detection, diagnosis and treatment  Nano wire and cantilever lab on chips help in early detection of cancer of diseases biomarkers. (Carcinoembryonic antigen –  Fig: The micro fluidic channel CEA; Alfa-fetoprotein-CEA; Prostate Specific with nano wire sensor can detect antigen –PSA) the presence of altered genes  Fig: The nano scale cantilever detects associated with cancer – J. Heath, Cali. the presence and concentration of Insti. of Technology various molecular expressions of a cancer cell – A. Majumdar, Univ. of Cal. at Berkeley
  • 14. Nanotechnology in Health Care - Thermal ablation of cancer cells  Thermal ablation of cancer cells − Nano shells have metallic outer layer and silica core kills the cancer cells by Thermal ablation − Selectively attracted to cancer shells either through a phenomena called enhanced permeation retention or due to some molecules coated on the shells
  • 15. Nanotechnology in Health Care - Treatment  Targeted drug deliver − Nano particles containing drugs are coated with targeting agents (e.g. conjugated antibodies) − The nano particles circulate through the blood vessels and reach the target cells − Drugs are released directly into the targeted cells
  • 16. Nanotechnology Based Drug Delivery  In biopharmaceuticals, in addition to the main technologies covered liposomal, monoclonal antibody-based, and polymer-based technologies host of newer technologies such as nano particles including various nano dimensional entities such as molecular imprinted polymers, pro drug delivery, oral, injectable and implantable, pulmonary, and transdermal and transmucosal delivery have come up.  Importance of Drug Delivery Technology to Pharma Industry 􀂉 Drug delivery formulations involve low cost research compared that for discovery of new molecule,
  • 17. Nanotechnology Based Drug Delivery � Minimizing the drug use would significantly reduce the effective cost of drug which would give financial relief to the patients, � Delivery systems increase commercial opportunity by distinguishing a drug from competitive threats posed by “me too” drugs and � Novel means of delivery particularly using nano-carriers, can allow branded drugs to be rescued from abyss of generic competition (may be called “resurrection of drug”).
  • 18. SOME SIGNIFICANT NANODEVICES  Development of one dose a day ciprofloxacin using nanotechnology  Tumor targeted taxol delivery using nano particles in Phase 2 clinical trial stage  Improved ophthalmic delivery formulation using smart hydrogel nano particles  Oral insulin formulation using nanoparticles carriers.  Liposomal based Amphotericin B formulation � Nano particles for Drug Delivery - Metal-based nano particles ; - Lipid-based nano particles - Polymer-based nano particles ; - Biological nano particles
  • 19. Nanotechnology Applications 1) SiO2-Nanoparticles as a new platform for non-viral gene delivery (favourable size 10 - 50 nm; controlled production possible; excellent phys.chemical stability ; many possibilities for chemical modification); Probably cheaper and safer, but presently not safer. 2) Using Nanotechnology for New Medicines: E.g. Gene-Therapy Modified genevector mRNA Therapeutic Protein
  • 20. Nanotechnology Applications 3) Brain Drug Targeting : Polysorbate-coated NPs to enhance penetration to the blood-brain barrier (BBB) – Mechanism: – Binding of the NPs to the inner endothelial lining of the brain capillaries (subsequently, particles deliver drugs to the brain by providing a large concentration gradient, thus enhancing the passive diffusion) – Brain endothelial uptake by phagocytosis _ A general surfactant effect characterized by a solubilization of the endothelial cell membrane lipids that would lead to membrane fluidization and an enhanced drug permeability through the BBB. _ The NPs could lead to an opening of the tight junctions between the endothelial cells. The drug could then permeate through the tight junctions in free form or together with the NPs in bound form
  • 21. Nanotechnology Applications _The NPs may be endocytosed by the endothelial cells followed by the release of the drugs within these cells and delivery to the brain. _The NPs with bound drugs could be transcytosed through the endothelial cell layer _The polysorbate 80 used as the coating agent could inhibit the efflux system, especially P- glycoprotein (P-gp) 4) Semiconductor Nano Crystals or “QUANTUM Dots TM ” or Biodegradable bio polymers for ex-vivo optical diagnostics and some form of hybrid biodegradable nano capsule with MRI contrast agent core for in-vivo simultaneous diagnostics and therapeutics (“theragnostics”).
  • 22. Nanotechnology Applications  Nanoelectromechanical System (NEMS) Sensors − NEMS technology enables creation of ultra small and highly sensitive sensors for various applications − The NEMS force sensor shown in the figure is applicable in pathogenic bacteria detection Fig : A NEMS bacteria sensor
  • 23. Nanotechnology Applications 5) Nano medicine - Continuous Therapy for Preventing Cancer in Astronauts: Engineered multilayered nano particles targeted to radiation-damaged cells can initiate repair of damaged DNA using DNA repair genes manufactured inside individual living cells under the control of molecular biosensor switches. 6) Nanoparticles in cancer therapy : 7) Targeted delivery of antibiotics using nanoparticles: Challenge is to design the means of Increase in antitumor efficacy; Reduction of systemic side-effects; Selective delivery of oligonucleotides to tumor cells ; Reversion of multidrug resistance in tumor cells; carrying an antibiotic in a form that is able to be endocytosed by phagocytic cells and then released into these cells. Nanoparticles are one of the main carriers developed for these logistic strategies
  • 24. Nanotechnology Applications Targeting of intracellular bacteria with antibiotic colloidal carriers: liposomes or nanoparticles.
  • 25. Nanotechnology Applications- DNA Sequencing 8) In DNA Sequencing: DNA molecules, under the influence of an electric field, are forced through nano-scale channels (~100 nm) on a “gel biochip”. The molecules deform and stretch to pass through the small channels.  This process separates DNA fragments by length.  This is part of the method used to sequence the DNA in the human genome and in identifying a unique DNA “fingerprint”.
  • 26. - Immunoisolation for Cell-encapsulation therapy Nanotechnology Applications 9) Liver Dysfunction: Encapsulation of Hepatic Cell Pancreas Dysfunction: Encapsulation of Islets of Langerhans Disorders of the CNS: Parkinson’s, Alzheimer’s Pre-requisites for cell encapsulation – continued and optimal tissue/cell supply – maintenance of cell viability & function – successful prevention of immune rejection Nonporous Silicone-based biocapsules serves as Artificial Pancreas(Desai et al.)
  • 27. Nanotechnology Applications 10) Targeting Tumours: « Smart Bombs »  Conventional Therapy: Chemotherapy that poisons surrounding tissue  Strategy: Block angiogenesis selectively at tumor site  Nanoparticle: DNA + Cationic Polymer directed at tumourous cells  Starves blood cells
  • 28. Nano engineering – Bio analogous Structures  Bone-cartilage composite ?  Muscle ?  Brain-machine Interface ?
  • 29. CHALLENGES & Methods of Drug Delivery  Prevention of drug from biological degradation (Oral dosage form)  Effective Targeting ( Inhalation)  Patient Compliance (Tran dermal)  Cost effectiveness (Implantation)  Product life extension (Injections)