The Use of Nanoparticles in Drug Delivery Systems: The Use of Nanoparticles in Drug Delivery Systems Presented by: P.Arsula II nd M.Tech Nanoscience &Technology Udaya school of engineering : Presented by: P.Arsula II nd M.Tech Nanoscience &Technology Udaya school of engineering Contents: 1.Introduction 2.Drug delivery 3.Nanoparticles in drug delivery 4.conclusion. : Contents: 1.Introduction 2.Drug delivery 3.Nanoparticles in drug delivery 4.conclusion . What is Nanotechnology?: What is Nanotechnology? Nanoscience: involves research and technology development at 1 nm to 100nm range (nanoscale) Nanotechnology creates and uses structures that have novel properties because of their small size Nanotechnology builds on the ability to control or manipulate at atomic scale Applications: Applications Medical Bio-materials Drug delivery Energy and industrial Solar / F uel Cells Lighting Coating and powders Paint Textiles Devices and microelectronics Sensors Microprocessors / memory and storage Nanomedicine: Nanomedicine • It is the medical application of nanotechnology. • It`s defined as the repair, construction and control of human biological systems using devices built upon nanotechnology standards. DRUG DELIVERY: -is the method or process of administering pharmaceutical compound to achieve a therapeutic effect in humans or animals.: DRUG DELIVERY: - is the method or process of administering pharmaceutical compound to achieve a therapeutic effect in humans or animals . TARGETED DRUG DELIVERY: Delivering a drug to a specific site in the body where it has the greatest effect, instead of allowing it to diffuse to various sites, where it may cause damage or trigger side effects. CONTROLLED DRUG DELIVERY - is one which delivers the drug at a predetermined rate , for locally or systematiclly , for specified period of time . : TARGETED DRUG DELIVERY: Delivering a drug to a specific site in the body where it has the greatest effect , instead of allowing it to diffuse to various sites, where it may cause damage or trigger side effects . CONTROLLED DRUG DELIVERY - is one which delivers the drug at a predetermined rate , for locally or systematiclly , for specified period of time . Methods of Drug Delivery: Methods of Drug Delivery 20/03/2008 Dept. of Pharmaceutics 9 Classical drug delivery: Classical drug delivery For most of the pharmaceutical industries existence, drug delivery induced simple, fast-acting responses via oral or injection delivery routes Problems associated with this approach Reduced potencies because of partial degradation Toxic levels of administration Increase costs associated with excess dosing Compliance issue due to administration pain What and Why: What and Why Nanoparticle – any particle that is sized between 1 to 100 nanometers (in terms of diameter) The use of nanoparticles allows one to change the pharmacokinetic properties of the drug without changing the active compound Advantges of nanoparticles in drug delivery:: Advantges of nanoparticles in drug delivery: Large surface-to-volume ratio resulting enhanced interaction sites Surface functionalization for targeting Suitable encapsulation Release drugs in controlled manner More efficient uptake by cells Types of Nanoparticles: Types of Nanoparticles Liposomes Nanopowders Micelle Polymeric nanoparticles Dendrimers Fullerenes Metal nanoparticles Magnetic nanoparticles Biological nanoparticles Liposomes: Liposomes a self-closing spherical particle that is composed of natural or synthetic amphiphilic lipid molecules -microscopic spherical vesicles that form when phospholipids are hydrated. METHODS OF DRUG LOADING: 1.Passive loading -these methods involve the loading of entrapped agents before or during the manufacturing procedure. 2.Active loading -some of the compounds with ionizable groups, and water solubility can be introduced into the liposomes after the formation of intact vesicles. -: METHODS OF DRUG LOADING: 1.Passive loading -these methods involve the loading of entrapped agents before or during the manufacturing procedure. 2.Active loading -some of the compounds with ionizable groups, and water solubility can be introduced into the liposomes after the formation of intact vesicles. - Slide 16: What is doxorubicin liposomal (Doxil)? Doxorubicin liposomal is a cancer (antineoplastic) medication. Doxorubicin liposomal interferes with the growth of cancer cells and slows their growth and spread in the body. Doxorubicin liposomal is used to treat metastatic ovarian cancer and AIDS-related Kaposi's sarcoma. Slide 17: Doxil is the drug doxorubicin HCl encapsulated in an antibody linked PEGylated liposome Composed of multiple monoclonal antibodies to target cancer cells PEG (polyethylene glycol) makes the liposome less vulnerable to immune system Lipid composition: mainly diastearoylphospatidylcholine and cholesterol - increases liposomal rigidity Slide 18: PEGylation, by increasing the molecular weight of a molecule , can impart several significant pharmacological advantages over the unmodified form, such as: Improved drug solubility Reduced dosage frequency, without diminished efficacy with potentially reduced toxicity Extended circulating life Increased drug stability Enhanced protection from proteolytic degradation Slide 19: Doxil works through passing through fenestrations in the vasculature and concentrating at tumor sites - Leads to reduced accumulation in other tissues Able to deliver the drug at moderate concentrations over a longer period of time Half life: 54 hours Result: An anticancer drug that is delivered more effectively - decreased side effects and dosage Doxil acts by the intercalation of DNA Nanopowder: Nanopowder 20/03/2008 Dept. of Pharmaceutics 20 Nanopowders:: Nanopowders: Nanopowders are powders composed of nanoparticles, that is particles having an average diameter below 50 nanometers (nm). Such compounds have two or more different cations (positively charged elements) in their chemical formula. An example of a complex compound is calcium titanate (CaTiO3). 20/03/2008 Dept. of Pharmaceutics 21 Micelle: Micelle Micelle is an aggregate of amphipathic molecules in water, with the nonpolar portions in the interior and the polar portions at the exterior surface, exposed to water. Hydrophobic drugs can be encapsulated, into inner core. 20/03/2008 Dept. of Pharmaceutics 22 Dendrimers: well_defined ,highly branched,three dimensional macro molecules with a large number of functional groups.: Dendrimers : well_defined ,highly branched,three dimensional macro molecules with a large number of functional groups. Polymeric Nanoparticles: Polymeric Nanoparticles Nanoparticles synthesized from polymers Entrapment or Encapsulation: Entrapment or Encapsulation During the 1970, scientists first began to encapsulate and entrap drugs within polymers Encapsulation involves surrounding drug molecules with a solid polymer shell Entrapment involves the suspension of drug molecules within a polymer matrix. drug polymer Drug Polymer Drug release by diffusion: Drug release by diffusion Early encapsulation and entrapment systems released the drug from within the polymer via molecular diffusion When the polymer absorbs water it swells in size Swelling created voids throughout the interior polymer Smaller molecule drugs can escape via the voids at a known rate controlled by molecular diffusion (a function of temperature and drug size) Add water Add time Treatment of Type 1 Diabetes: Treatment of Type 1 Diabetes Type I diabetes – autoimmune disorder that results in destruction of insulin-producing beta cells of the pancreas - treatment includes insulin therapy The polymer will hopefully be able to provide the correct amount of insulin, regardless of blood sugar levels Nanoshells: Nanoshells Developed by Drs. Naomi Halas and Jennifer West – Rice University 1994 Nanoshells have a core of silica and a metallic outer layer. These nanoshells can be injected safely, as demonstrated in animal models. Because of their size, nanoshells will preferentially concentrate in cancer lesion sites. This physical selectivity occurs through a phenomenon called enhanced permeation retention (EPR). Can further decorate the nanoshells to carry molecular conjugates to the antigens that are expressed on the cancer cells themselves or in the tumor microenvironment. This second degree of specificity preferentially links the nanoshells to the tumor and not to neighboring healthy cells. http://singularityhub.com/2009/12/14/nih-guides-nanomedicine-towards-killing-cancer/ Nanoshells: Nanoshells http://blogs.chron.com/sciguy/archives/2008/07/at_long_last_na.html Carbon 60: Carbon 60 20/03/2008 Dept. of Pharmaceutics 32 Carbon 60 : Carbon 60 C60 are spherical molecules about 1nm in diameter, comprising 60 carbon atoms arranged as 20 hexagons and 12 pentagons: the configuration of a football. Hence they find application as NanoPharmaceuticals with large drug payload in their cage like structure. On the other hand with development of various chemical substitutes for C60, it is possible to develop functionalized C60 with better drug targeting properties 20/03/2008 Dept. of Pharmaceutics 33 Carbon Nanotube: Carbon Nanotube Carbon nanotubes are adept at entering the nuclei of cells and may one day be used to deliver drugs and vaccines. The modified nanotubes have so far only been used to ferry a small peptide into the nuclei of fibroblast cells. But the researchers are hopeful that the technique may one day form the basis for new anti-cancer treatments, gene therapies and vaccines. 20/03/2008 Dept. of Pharmaceutics 35 Gold nanoparticles -carboplatin: Gold nanoparticles - carboplatin Iron oxide nanoparticles -human serum albumin -doxorubicin : Iron oxide nanoparticles - human serum albumin -doxorubicin Slide 38: Viral vectors Viruses have evolved a way of encapsulating and delivering genes to human cells in a pathogenic manner. Scientist are attempting to take advantage of natures delivery system. Viruses would be genetically altered to carry the desired normal gene and turn off the natural occurring disease within the virus. [Video from www.biosciednet.org/portal] Mechanism of action:: Mechanism of action: TRANSDERMAL PATCHES: -Drug which passively diffuses through the skin. Advantages: 1)No pain 2)No missing of dose 3)continuous drug delivery : TRANSDERMAL PATCHES : - Drug which passively diffuses through the skin. Advantages: 1)No pain 2)No missing of dose 3)continuous drug delivery Slide 41: Implantable Drug Delivery Delivery rate may be externally controlled or osmotically or peristaltically controlled with the aid of transcutaneous monitoring. Nanobot in medicine: Nanobot in medicine early diagnosis and targeted drug delivery for cancer, biomedical instrumentation, surgery, monitoring of diabetes, and health care employ nanobots injected into the patient to perform treatment on a cellular level improve the presence of drug molecules where they are needed in the body and where they will do the most good Conclusion: Conclusion The development of particles that are nanoscaled has created great opportunities in the development of improved drug delivery systems. 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