Presentation is loading. Please wait.

Presentation is loading. Please wait.

Micro- and Nano- Therapeutics Joseph F Chiang Department of Chemistry and Biochemistry State University of New York College at Oneonta Nanotechnology and.

Similar presentations


Presentation on theme: "Micro- and Nano- Therapeutics Joseph F Chiang Department of Chemistry and Biochemistry State University of New York College at Oneonta Nanotechnology and."— Presentation transcript:

1 Micro- and Nano- Therapeutics Joseph F Chiang Department of Chemistry and Biochemistry State University of New York College at Oneonta Nanotechnology and Applications October 16, 2004

2 Micro- and Nano-Therapeutics Nanotechnology –to build matter from atoms/molecules-bottom-up technique. from atoms/molecules-bottom-up technique. All matters were built historically with top-down technique. Chemistry is a nanotechnology- combines atom/molecules to build bulk materials.

3 Characteristics of Common Routes of Drug Administration

4 Quantum Wells, Wire and Dots Quantum wells: if one dimension is reduced to nanoscale while the other two remain large. Quantum wells: if one dimension is reduced to nanoscale while the other two remain large. Quantum wires: if 2 dimensions reduced to nanoscale while the third one remains large. Quantum wires: if 2 dimensions reduced to nanoscale while the third one remains large. Quantum dots: if all 3 dimensions reach nanoscale Quantum dots: if all 3 dimensions reach nanoscale

5 Approximate Sizes and Molecular Weight of several Proteins d=size parameter of fundamental, d=size parameter of fundamental, biological building block: biological building block: d=.12(MW) 1/3 (nm) d=.12(MW) 1/3 (nm) MW= molecular weight in unit of dalton. MW= molecular weight in unit of dalton.

6 ProteinMW Size _________ Hemoglobin68KDa4.5x7nm ProteinMW Size _________ Hemoglobin68KDa4.5x7nm Lipoprotein130KDa20 nm Lipoprotein130KDa20 nm -globulin90KDa4.3x26 nm -globulin90KDa4.3x26 nm Fibrinogen406KDa4x76 nm Fibrinogen406KDa4x76 nm

7 Polypeptide nanowire: In a manner, amino acids combine together in chain by formation of peptide bond.

8 DNA double nanowire: Basic building block of DNA is nucleotide, it is a five member ring deoxyribose with phosphate group, a nucleic acid base R.

9 Drug Delivery System Technologies Oral Drug Delivery Oral Drug Delivery Injection Based Drug Delivery Injection Based Drug Delivery Transdermal Drug Delivery Transdermal Drug Delivery Bone Marrow Infusion Bone Marrow Infusion

10 Organ System Specific Drug Organ System Specific Drug Delivery: Delivery: a. Pulmonary Drug Delivery a. Pulmonary Drug Delivery b. Nasal Delivery to Central b. Nasal Delivery to Central Nervous System(CNS) Nervous System(CNS) c. Cardiovascular System(CV) c. Cardiovascular System(CV) d. Gastro-Intestinal tract(GI) d. Gastro-Intestinal tract(GI) e. Genito-Urinary Tract(GU) e. Genito-Urinary Tract(GU) f. Ocular Drug Delivery f. Ocular Drug Delivery

11 Control Release Systems Control Release Systems Novel Packaging and Formulations: Novel Packaging and Formulations: a. Fast Dissolving Tablets a. Fast Dissolving Tablets b. Chewable Tablets b. Chewable Tablets c. Solubility Enhancement c. Solubility Enhancement

12 Targeted Drug Delivery: Targeted Drug Delivery: a. Polymer and Collagen System a. Polymer and Collagen System b. Particle-based system b. Particle-based system 1. Therapeutical Monoclonal 1. Therapeutical Monoclonal antibodies antibodies 2. Liposomes 2. Liposomes 3. Microparticles 3. Microparticles

13 4. Modified Blood Cells 4. Modified Blood Cells 5. Nanoparticles 5. Nanoparticles 6. Viral Assisted Intracellular Gene 6. Viral Assisted Intracellular Gene delivery delivery 7. Non-Viral Intracellular Gene 7. Non-Viral Intracellular Gene delivery delivery Implant Drug Delivery System Implant Drug Delivery System

14 Goals of Nano-therapeutics 1. Ways to treat Disease

15 2. Implants:

16 Requirements of Nano therapeutic Applications Devices should be non-invasive Devices should be non-invasive Devices target therapeutics payloads to site of disease. Devices target therapeutics payloads to site of disease. Devices should maximize therapeutic benefit and minimize undesired side effect Devices should maximize therapeutic benefit and minimize undesired side effect

17 Characteristics of Therapeutic Nanodevices : 1. Biological molecule must retain functions. functions. 2. Device function is the result of the activities of device component. activities of device component. 3. The relative organization of device component drives device function. component drives device function. 4. Device function can be unprecedented in the biological unprecedented in the biological world. world.

18 Characteristics of Nanobiological Device Device 1. Minimally invasive 2. Target sites of disease 3. Sense disease states in order to: - report conditions at the disease site to - report conditions at the disease site to clinicians; clinicians; - administer metered therapeutic - administer metered therapeutic interventions. interventions. 4. Therapeutic function should be segregated into standard modules segregated into standard modules 5. Modules should be interchangeable to tune therapeutic functions. tune therapeutic functions.

19 Bionanotechnology Applications for design and construct materials at nanoscale in biotechnology field. Bionanotechnology-from natural enzyme to manipulate genetic code in order to modify organisms. Biomaterials –result of application of bionanotechnology.

20 Biomachines- to design molecular machines at nanoscale, for example, study of cancer cells. There are hundred-thousand different nanomachines inside human body.

21 Purpose of Nano-therapeutics Discussions Focused on nanodevices rather than nanomaterials. Purpose- serves as integral component of drug delivery or other clinical devices. Incorporating biological structure into nanobiological devices: special challenge with traditional engineering design

22 Nanocontainers To deliver drug directly to cells. (The effective drug treatment is getting the medication to exactly the right spot) Research report in “Science”: Methods to develop tiny containers of nanocomposites to distribute drugs to specific spot within individual cells.

23 Radoslav Aavic at McGill has developed two types of polymers- Micelle: Hydrophobic end facing inward, Hydrophilic end facing outward Dimension: 20-45 nm. Dimension: 20-45 nm. Using fluorescent light to tack the micelle’s journey and discovered the tiny container could pass through the wall of a rat cell, but did not enter the cell’s nucleus. It also did not penetrate other part of the cell, as mitochondria.

24 Nanoceramic drug delivery system 1. Reducing toxicity to non-diseased 1. Reducing toxicity to non-diseased cells cells 2. Increasing drug efficiency 2. Increasing drug efficiency 3. Being able to target and control 3. Being able to target and control drug release with high precision drug release with high precision (Several anti-cancer drugs fail in their desired clinical activity due to lack of specific target delivery.) (Several anti-cancer drugs fail in their desired clinical activity due to lack of specific target delivery.)

25 An Example: An Example: Glass microsphere of 17Y 2 O 3 -19Al 2 O 3 - 64SiO 2 (mol %) composition, 20-30 m diameter-effective for targeted radiotherapy of liver cancer( 89 Y is non-radioactive, can be activated by neutron bombardment to 90 Y, a - emitter(t ½ =64.1 h) Glass microsphere of 17Y 2 O 3 -19Al 2 O 3 - 64SiO 2 (mol %) composition, 20-30 m diameter-effective for targeted radiotherapy of liver cancer( 89 Y is non-radioactive, can be activated by neutron bombardment to 90 Y, a - emitter(t ½ =64.1 h)

26 Nanomedicine One of the great promises of nanotechnology- to increase control of our personal health. Understanding of disease-open the door to therapy for treating disease. Nanotherapeutic is one the nanotechnology applications in treating disease. Nanotherapeutic is one the nanotechnology applications in treating disease.

27 Nanotherapeutic devices are created to find the target and to correct it. Nanotherapeutic devices are created to find the target and to correct it. Immunotoxins-one component binds to target cells, the other component is the poison that kills the cell. Immunotoxins-one component binds to target cells, the other component is the poison that kills the cell.

28 Liposomes-artificial membranes, under specific conditions forming small, closed vesicles composed of a lipid bilayer that encloses a small droplet of water. Liposomes-artificial membranes, under specific conditions forming small, closed vesicles composed of a lipid bilayer that encloses a small droplet of water. Liposome size-20 nm-10m to deliver drug. Liposome size-20 nm-10m to deliver drug.

29 Gene Therapy- with understanding of human genome, one can understand and correct genetic defect. Gene Therapy- with understanding of human genome, one can understand and correct genetic defect. Therapy is to correct a missing or defect protein. Therapy is to correct a missing or defect protein.

30 Current Applications Current Applications Injection of the spheres into a diseased liver through the hepatic artery where they are entrapped in small blood vessels to block blood supply to cancer cells and irradiating β ray to cancerous cells. irradiating β ray to cancerous cells.

31 An Example: The development of Targeted Nano Therapeutics(TNT): ( by Triton BioSystem with Army Research Lab)

32 (Continue) The TNT system attacks cancer in 3 steps. 1. The patient receives a simple infusion containing trillions of bioprobes, each of which is a nanoscale magnetic sphere bound to an antibody, 2. The bioprobes will seek and attach to cancer cells in the bloodstream,

33 (Continued) 3. The physician will switch on the magnetic field in the region of the cancer. This will cause the bioprobes to heat up to kill the cancer cells within minutes.

34 Another example: A tumor or cancerous cell can be destroyed at 43 o C. Normal cells can be kept alive at ~49 o C. When ferri- or ferro-magnetite materials are implanted, heating at alternating magnetic field can kill the cancerous cells. If the pore of the magnetic materials is decreased to nanoscale, cancer cells can be destroyed.

35 Use of ferromagnetic glass ceramic containing 36 wt% of magentite(Fe 3 O 4 ), 200nm diameter in CaO-SiO 2 matrix. containing 36 wt% of magentite(Fe 3 O 4 ), 200nm diameter in CaO-SiO 2 matrix. The cancerous cells in the canal of rabbit tibia were destroyed when the device is inserted into tibia and placed under an alternating magnetic field of 300 Oe at 100 KHz.(Kokubo, et al.)

36 1. Nanotherapeutic Device in Oncology Existing therepies-surgical, resection, radiotherapy, and chemotherapy- unfavorable. Nanotherapeutic devices can be specifically delivered to tumor by virtue of the size, Therapeutic devices with cytoxins can not leave the normal cells, but can leak to tumor cells.

37 2. Cardiovascular Application of Nanotherepeutics: Current tissue engineering approaches involve synthesis of 3-D, porous scaffolds that allow, adhesion, growth, and proliferation of seeded cells to generate functional vessel. Current tissue engineering approaches involve synthesis of 3-D, porous scaffolds that allow, adhesion, growth, and proliferation of seeded cells to generate functional vessel. MEMS technology and nanoscale control of molecular events &interaction has been applied to the development of cardiovascular sensors. MEMS technology and nanoscale control of molecular events &interaction has been applied to the development of cardiovascular sensors.

38 3. Nanotherapeutics & Specific Host Immune Responses 4. Nanotherapeutic Vaccines 5. Antibody Response to Therapeutic Devices. Therapeutic Devices. 6. Special Device Application.

39 a. Biosensors detect glucose level for management of Diabetes: a. Biosensors detect glucose level for management of Diabetes: Implanted sensors and non- invasive sensors are underdevelopment to monitor glucose level with glucose oxidase which combine glucose and O 2 to form gluconic acid and H 2 O 2. Pt electrode is used to measure H 2 O 2 level. Implanted sensors and non- invasive sensors are underdevelopment to monitor glucose level with glucose oxidase which combine glucose and O 2 to form gluconic acid and H 2 O 2. Pt electrode is used to measure H 2 O 2 level.

40 b. A biosensor using hemolysin to detect short strand of DNA. Hemolysin is embedded in a membrane separating 2 chambers which draws ions from one to another. When nanopores are blocked, an abrupt change in current is detected(Chamber dimensions: one with 3-4 nm in diameter and the other with 1.4 nm in diameter). b. A biosensor using hemolysin to detect short strand of DNA. Hemolysin is embedded in a membrane separating 2 chambers which draws ions from one to another. When nanopores are blocked, an abrupt change in current is detected(Chamber dimensions: one with 3-4 nm in diameter and the other with 1.4 nm in diameter).

41 c. Antibodies used as a biosensor for blood type tester-composed of a collection of antibodies that recognize specific sugars on the surface of red blood cells. The antibody is added to the blood, and if the particular blood type is present in the cells, the antibody is bind to the surface, sticky cells together. The result is that a clumping of cells can be detected by human eye. c. Antibodies used as a biosensor for blood type tester-composed of a collection of antibodies that recognize specific sugars on the surface of red blood cells. The antibody is added to the blood, and if the particular blood type is present in the cells, the antibody is bind to the surface, sticky cells together. The result is that a clumping of cells can be detected by human eye.

42

43 Soft Lithography

44 Synthesis of Poly (amido) amine (PAMAM) (Bottom-Up Approach)

45 Top-down Approach: Carbon nanotubes can be synthesized with a top-down approach from graphite Carbon nanotubes can be synthesized with a top-down approach from graphite sheets in an electric arc oven by sheets in an electric arc oven by metal catalyzed polymerization method. metal catalyzed polymerization method.

46 Bottom-up Approach: Proteins are synthesized from lower Proteins are synthesized from lower molecular weight amino acid precursors by chemically or biologically mediated molecular weight amino acid precursors by chemically or biologically mediated Polymerization. Polymerization.

47 Micro and Nanotechnology in Drug Delivery Synthesis and Preparations of nanoporous inorganic & organic platforms Synthesis and Preparations of nanoporous inorganic & organic platforms Use of biomolecules for targeting, adhesion, and biointerfacing Use of biomolecules for targeting, adhesion, and biointerfacing Nanofabricated & micropatterned drug delivery device Nanofabricated & micropatterned drug delivery device Formation & fabrication of nanoparticulate system modified with natural biological ligands. Formation & fabrication of nanoparticulate system modified with natural biological ligands.

48 Present Focuses of Therapeutic Delivery System Patients & Physicians Patients & Physicians Improve drug delivery and efficacy Improve drug delivery and efficacy Enhance drug stability Enhance drug stability Increase compliance Increase compliance Potential for local delivery-decrease site- effect Potential for local delivery-decrease site- effect

49 How Can Micro and Nanotechnology Help? Micro and nanofabrication allow for: Micro and nanofabrication allow for:  Control for shape  Control for size  Asymmetrical 3D design

50 Oral Drug Delivery

51 The Current Drug Delivery System Market Size: $50 billions for 2003, $67 billions for 2006( projected to grow) The total pharmaceutical market is $250 billions in 2001.

52 Nanotech Medicine NCI has launched a five-year initiative to enlist nanotechnolgy to fight cancer. $144 millions for the next five years to support the initiative. $90 millions will go toward funding several Centers of Cancer Nanotechnlogy Excellence. $38 millions for targeted research grant in the nanotech to fight against cancer $16 millions set aside to train scientists to work in this multidisciplinary environment.

53 Nanoceramics for Gene & Drug Delivery Layered double hydroxides(LDHs)- Gene or drug delivery into biological Gene or drug delivery into biological cells-a gene or drug delivery carrier cells-a gene or drug delivery carrier

54 Composition of LDHs: M(II) 1-x M(III) x (OH) 2 (A n- ) x/n yH 2 O, Where M(II)-divalent cation M(III)-trivalent cation, M(III)-trivalent cation, A =interlayer anion, A =interlayer anion, n-=charge on the interlayer ion. n-=charge on the interlayer ion. (Inorganic or organic anions can be introduced between hydroxide layer (Inorganic or organic anions can be introduced between hydroxide layer by ion exchange or precipitation.) by ion exchange or precipitation.)

55 Bio-LDH Nanohybrids Biofunctional molecules- nucleoside monophosphates, ATP, DNA, flourescein-5-isothiocyanate, etc can be intercalated into hydroxide layer To form bio-LDH nanohybrids

56 Controlled Release of Interlayer Biomolecules: The miomolecules stored in LDH’s can be released under acidic condition.

57 Preparation of Nanoparticles of LDHs The particles prepared in nanoscale for Intravenousinjection.

58 Number of Issued and Pending Patents and Number of papers relating to Nanotube Applications Number of Issued and Pending Patents and Number of papers relating to Nanotube Applications ____________________________________________ ____________________________________________ TopicsIssuedPendingPapers TopicsIssuedPendingPapers Production5992 1189 Production5992 1189 Field-emission-related Field-emission-related devices3058 394 devices3058 394 Electronics1127 360 Electronics1127 360 Composites, fibers 7 36 111 Composites, fibers 7 36 111 Sensors, probes,detectors 723 129 Sensors, probes,detectors 723 129 Hydrogen storage, fuel cells 4 2 63 Hydrogen storage, fuel cells 4 2 63 Batteries, capacitors 4 3 3 Batteries, capacitors 4 3 3 Other 30 33 3776 Other 30 33 3776 ___________________________________________________________ ___________________________________________________________ Total 152274 6026 Total 152274 6026

59 Identity Badge under skin FDA has approved “VeriChips” manufactured by Applied Digital Solution (Delray, Florida) to market implantable microchips under skin. An under-the–skin ID to access medical information. An under-the–skin ID to access medical information.


Download ppt "Micro- and Nano- Therapeutics Joseph F Chiang Department of Chemistry and Biochemistry State University of New York College at Oneonta Nanotechnology and."

Similar presentations


Ads by Google