Targeted drug delivery system
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Targeted drug delivery system
- 1. Mr. Shashank Chaurasiya Asst. Professor Bansal College of pharmacy, Bhopal
- 2. S. No. CONTENTS 1. INTRODUCTION 2. DIFFERENCE BETWEEN : TARGETED & CONVENTIONAL DRUG DELIVERYSYSTEM 3. DRUG TARGETING STRATEGIES 4. CARRIER CONCEPTS IN DRUG DELIVERY 5. SITE-SPECIFIC DRUG DELIVERY 6. MARKETED PREPARATIONS 7. CURRENT MARKET SALES DATAOF TDDS 8. CONCLUSION 9. REFERENCES
- 3. Targeted drug delivery means accumulation of pharmacologically active moiety at desired target in therapeutic concentration at the same restricting its access to normal cellular lining, thus minimizing therapeutic index. The drug can be targeted to intracellular sites, virus cells, bacteria cell and parasites using different scientific strategies have proven highly effective.[1] HISTORY The concept of targeted drugs is not new, but dates back to 1906 when Ehrlich first postulated the āmagic bulletā. The durability of this concept is a strong indication of its appeal, but the āmagic bulletā continues to be a challenge to implement in the clinic.
- 4. Sr. no. Targeted Drug Delivery System Conventional Drug Delivery System 1. Specific Location Equally distributed 2. High efficacy Lower efficacy 3. Less side effects More side effects 4. Low frequency High frequency 5. Low fluctuation in circulating drug levels High fluctuation in circulating drug levels DIFFERENCE BETWEEN : TARGETED & CONVENTIONAL DRUG DELIVERY SYSTEM
- 6. 1. Passive Targeting :- Drug delivery systems which are targeted to systemic circulation are characterized as Passive delivery systems. The ability of some colloid to be taken up by the Reticulo Endothelial Systems (RES) especially in liver and spleen make them ideal substrate for passive hepatic targeting of drugs. 2.Inverse Targeting:- In this type of targeting attempts are made to avoid passive uptake of colloidal carrier by RES and hence the process is referred to as inverse targeting.
- 7. 3. Active Targeting :- In this approach carrier system bearing drug, reaches to specific site on the basis of modification such as coating of surface with either a bioadhesive, nonionic surfactant or specific cell or tissue antibodies (i.e. monoclonal antibodies) or by albumin protein are made on its surface rather than natural uptake by RES 4. Ligand-mediated Targeting :- Ligand-targeted nanoparticles bind selectively to target cells, such as tumor cells.
- 8. 5. Physical Targeting :- The external triggers can be employed both with and without active targeting. In the case of only external triggers being used, then the targeting strategy is known as āphysical targetingā. The commonly employed external triggers are ultrasound, magnetic field, electric field and infrared radiation. 6.Dual Targeting :- In this targeting approach carrier molecule itself have their own therapeutic activity and thus increase the therapeutic effect of drug. For example, a carrier molecule having its own antiviral activity can be loaded with antiviral drug and the net synergistic effect of drug conjugate was observed.
- 9. 7. Double Targeting :- The combination is made between spatial control & temperature controlled drug delivery ,when these two methodologies are combined, it is called as Double targeting.
- 10. 8. Combination Targeting :- The use of both external triggers and active targeting is known as ācombined targetingā. External triggers can also be used along with passive targetingand forms a subset of combined targeting.
- 11. 1.LIPOSOMES 2.NIOSOMES 3.SUBMICRON EMULSIONS 4.MULTIPLE EMULSIONS 5.NANOPARTICLES 6.RESEALED ERYTHROCYTES 7.MICROSPORES 8.MAGNETICALLY MODULATED DRUG DELIVERY
- 12. 1.LIPOSOMES Liposomes were first described by Bangham in 1965. The name liposome is derived from two Greek words: 'Lipos' meaning fat and 'Somaā meaning body. Mechanisms of Liposomes: 1. Liposome attaches to cellular membrane and appears to fuse with them, releasing their content into the cell. 2. They are taken up by the cell and their phospholipids are incorporated into the cell membrane by which the drug trapped inside is released 3. In case of Liposomes phagocyte are taken cell, the up, the phospholipid walls are acted upon by organelles called lysosomes and the active pharmaceutical ingredients are released.
- 13. APPLICATION OF LIPOSOMES IN PHARMACEUTICALINDUSTRY Sr. No. Liposome Utility Examples Disease States Treated 1. Sustained- Release Systemic antineoplastic drugs, hormones, corticosteroids, drug depot in the lungs Cancer, bio therapeutics 2. RES Targeting Immuno modulators, vaccines, antimalarials, macrophage-located diseases Cancer, MAI, tropical parasites 3. Site-Avoidance Amphotericin B ā reduced nephrotoxicity, doxorubicin ā decreased cardiotoxicity Fungal infections, cancer 4. Drug protection Cytosine arabinoside, interleukins Cancer 5. Specific Targeting Cells bearing specific antigens Wide therapeutic applicability
- 14. Sr. No. Liposome Utility Examples Disease States Treated 6. Extra vasation Leaky vasculature of tumours, inflammations, infections Cancer, bacterial infections 7. Accumulation Prostaglandins Cardiovascular diseases 8. Enhanced penetration Prostaglandins Cardiovascular diseases 9. Drug depot Lungs, subcutaneous, intramuscular, ocular Wide therapeutic applicability
- 15. 2.NIOSOMES A Niosome ionic surfactant-based formed mostly is a non- Vesicle by nonionic surfactant and an excipient. They cholesterol incorporation as are structurally similar to liposomes in having a bilayer, however, they are more stable than liposomes.
- 17. 3.SUBMICRON EMULSIONS Submicron emulsion can be defined as emulsions with mean droplet diameters ranging from 50 to1000 nm. Usually, the average droplet size is between 100 and 500 nm. The globules can exist as water-in-oil and oil-in-water forms,where the core of particle is either water or oil, respectively. Limitation of submicron emulsion The main limitation of submicron emulsion is use of high amount of surfactant and cosurfactant that may be harmful for human consumption.
- 18. ADVANTAGES OF SUBMICRON EMULSION[7] Thermodynamically Stable Ease of manufacturing and scale-up Improved drug solubilization & bioavailability Wide application in colloidal drug delivery systems
- 19. 4.MULTIPLE EMULSIONS Multiple emulsions are the emulsion systems in which the dispersed phase contains smaller droplets that have the same composition as the externalphase. This is made possible by āDouble Emulsificationā. There are 2 types of Multiple Emulsions : MULTIPLE EMULSIONS Oil-in-water-in- oil (O/W/O) emulsion system Water-in-oil-in- water (W/O/W) emulsion system
- 20. BIOMEDICAL & PHARMACEUTICALAPPLICATIONS OF MULTIPLE EMULSIONS Sr. No. Applications Drugs Entrapped (Examples) 1. Enhanced Oral Bioavailability Heparin, Insulin, Griseofulvin 2. MaskingAction Chlorpromazine HCL, Chloroquin 3. Enzyme Immobilization Urease, Lipase, Amylase,Pancreatic enzymes 4. VaccineAdjuvants Influenza virus, Tetanus toxoid 5. Drug over Dosage treatment Salicylates, Barbiturates, Quinine sulphate 6. In Cancer therapy & drug targeting Methotrexate, Cysteamine,Adriamycin HCl 7. OtherApplications Food & Cosmetics
- 21. 5.NANOPARTICLES
- 22. Polysaccharides ProteinsSynthetic polymers Rolland et. al., (1989) designed a site specific drug delivery system consisting of polymetacryclic nanoparticles. The main goal in designing nanoparticles as a delivery system are to control size of particle, surface characteristics and discharge of pharmacologically active agents in order to achieve the site specific action of the drug at the therapeutically optimal rate and dose regimen. Preparation PARTICLE SIZE 1.Ultrafine particles -1 and 100 nm in size. 2.Fine particles -100 and 2,500 nm. 3.Coarse particles -2,500 and 10,000 nm.
- 24. APPLICATIONS Cancer therapy MATERIAL PURPOSE Poly (alkyl cyanoacrylate) Targeting, reducing toxicity, enhanced nanoparticles with anti cancer agents, uptake of anti tumour agents, oligo nucleotides improved invitro and invivo stability Intracellular targeting Poly (alkyl cyanoacrylate) polyester Target reticuloendothelial intercellular nanoparticles with anti parasitic or infections Prolonged systemic circulation anti viral agents Poly esters with adsorbed ethylene glycols or pluronics poly Prolonged systemic drug effect, avoid uptake by the reticuloendothelial system Vaccine adjuvant Poly (methyl methacrylate) Enhanced immune response alternate nanoparticles with vaccines (oral and acceptable adjuvant Peroral absorption IM immunization) Poly (methyl nanoparticles with therapeutic agents protectionmethacrylate) Enhanced bioavailability proteins and from GIT enzymes
- 25. Ocular delivery Poly (methyl nanoparticles with inflammatory agents, anti-bacterial agents for glaucoma methacrylate) Improved retention of drug/ steroids , anti- reduced wash out Oligonuleotide delivery ofAlginate nanoparticles , poly (D,L ā Enhanced delivery lactic acid) nanoparticles oligonucleotides DNAdelivery DNA- gelatin nanoparticles, DNA- Enhanced delivery and chitosin nanoparticles significantly higher expression levels Other applications Poly (alkyl cyanoacrylate) Crosses blood-brain nanoparticles with peptides Poly (alkyl immunoassays, barrier, improved cyanoacrylate) nanoparticles, absorption and permeation for nanoparticles with adsorbed enzymes, transdermal applications, nanoparticles with radioactive or enzyme immunoassays, radio contrast, copolymerized peptide imaging agents, oral delivery of nanoparticles of activated peptides peptides
- 26. 6.RESEALED ERYTHROCYTES Erythrocytes, the most abundant cells in the human body, have potential carrier capabilities for the delivery of drugs. Erythrocytes biodegradable, are biocompatible, possess very long circulation half lives and can be loaded with a variety of chemically biologically active compounds and using various chemical and physical methods. Application of erythrocytes as promising slow drug release or site- targeted delivery systems for a variety of bioactive agents from different fields of therapy has gained a remarkable degree of interest in recent years.
- 27. METHODS OF DRUG LOADING Osmotic Shock Turbulence Shock Erythrocyte Sedimentation Rate (ESR) Use of red cell loader Hypotonic dilution Chemical perturbation of the membrane Entrapment by endocytosis Loading by electric cell fusion Loading by lipid fusion
- 28. APPLICATIONS OF RESEALED ERYTHROCYTES [9] Slow drug release Enzyme deficiency/r eplacement therapy Treatment of hepatic tumors Treatment of parasitic diseases Removal of RES iron overloadRemoval of toxic agents Delivery of antiviral agents Enzyme therapy Improvement in oxygen delivery to tissues Microinjection of macromolecules
- 29. 7.MICROSPHERE SMicrospheres as carriers of drug become an approach of controlled release dosage form in novel drug delivery system. Microspheres are sometimes referred to as microparticles. Microspheres can be prepared from variousnatural and synthetic materials. Polymer microspheres, Glass microspheres and ceramic microspheres are commercially available.[1] Common types of polymer microspheres :- 1.Polyethylene microspheres 2. Polystyrene microspheres
- 30. APPLICATIONS [8] In vaccine delivery In immune system Targeting using microparticulate carriers Magnetic microspores Immuno- microspheres Chemo- embolization Imaging Micro-sponges Surface modified microspheres
- 31. 8.MAGNETICALLY MODULATED DRUG DELIVERY Magnetic drug delivery is a novel approach to deliver drug using engineered āsmartā micro carriers which appears to overcome a number of limitations facing current methods of delivering medicines. ļ Principle of Magnetism for micro particles Magnetic carriers are normally grouped according to size. At the lower end, we have the ferrofluids, ļ which are colloidal iron oxide solutions. Encapsulated magnetite particles in the range of 10ā500 nm are usually called magnetic nanospheres and any Magnetic particles of just below 1ā100Āµm are magnetic microspheres. In general, magnetic liposomes are also included when speaking about magnetic carriers
- 32. Mechanism 1.The release of macromolecules from EVAc systems without magnetic beads, suggests that molecules with molecular weight greater than 300 cannot permeate the polymer. 2.The direct incorporation of macromolecules in the polymer-macromolecule using cast procedure caused a tortuous and complex series of pores formation within the matrix. 3.The release rates are determined by factors affecting permeation of water into the polymer and drug out of these pores. Applications of MMDD Contraceptive Drug Delivery Infusion PumpsImplants
- 34. SITE SPECIFIC DRUG DELIVERY Brain Bone marrow Pulmonary Colon targeted Transdermal Vagina Ocular drug delivery Oncology Gastro- Retentive Drug Delivery
- 36. Rate-limiting role of the BBB in brain drug development : BBB have efficient ability to restrict and separate the human brain from circulatory network & also limits the transport of water and lipidsoluble substances from blood circulation into CNS.
- 37. Osmotic & Chemical opening of BBB By passing the BBB Direct invasive methods Various pharmacological agents to unblock the BBB Strategies utilized to manipulate BBB to target brain
- 42. DRUG DELIVERY DEVICES Metered Dose Inhalers Dry Powder Inhalers Nebulizers
- 44. The transdermal drug delivery system is a therapeutic system designed to transfer drugs through intact skin for systemic treatment & it offers controlled drug release pattern by a simple application to the skin surface, eliminating the gastrointestinal absorption associated with oral administration and providing for more efficient drug utilization. COMPONENTS OF TRANSDERMAL DEVICES
- 47. 4. DRUG TARGETING TO BONE MARROW
- 48. Development of effective targeted bone marrow drug delivery systems is an important goal for development of diagnostic, protective, and therapeutic agents for hematopoietic disorders and infectious diseases in which colonizing pathogens are difficult to eradicate. DISEASES CURED Aplastic Anaemia Hodgkinās disease Leukaemia Multiple Myeloma Thalassemia Peripheral stem cell transplants
- 51. To achieve successful colonic delivery, a drug needs to be protected from absorption and /or the environment of the upper gastrointestinal tract (GIT) and then be abruptly released into the proximal colon, which is considered the optimum site for colon- targeted delivery of drugs.
- 59. Vaginal drug delivery system offers an avenue for the release of different antifungal, antibacterial and contraceptive drugs. Conventional vaginal dosage forms have several benefits like :- 1.Avoid the first pass metabolism 2.Easy to formulate 3.Self administration is possible 4.Economical. DOSAGE FORMULATIONS Controlled/ Sustained release vaginal tablets Vaginal Nanoparticles Vaginal Microspheres Vaginal Rings
- 62. Targeted drug delivery in oncology provides a localized and prolonged drug delivery to the affected organ or tissues.The treatment of cancer depends upto the stage to which the cancer has progressed.
- 63. CARRIERS BIOPOLYMERS EMULSIONS LIPOSOMAL HYDROGELS MICROPARTICLES POLYETHYLENE GLYCOL CONJUGATION
- 66. Gastroretentive drug delivery is an approach to prolong gastric residence time, thereby targeting site-specific drug release in the upper gastrointestinal tract (GIT) for local or systemic effects. FACTORS CONTROLLING GASTRIC RETENTION Density of dosage forms Density of dosage forms Food intake and its nature Effect of gender, posture and age
- 67. APPROACHES High density (sinking) system or non- floating system Floating drug delivery systems Non- effervescent Systems Hydrodynamically balanced systems Microballoons / Hollow microspheres Alginate beads Effervescent (gas generating) systems Bioadhesive or Mucoadhesive drug delivery systems Super porous hydrogel systems Magnetic Systems
- 69. FORMULATION OF FLOATING HOLLOW MICROSPHERE OR MICROBALLOON
- 70. Sr. no. Name of preparation : Manufacturer Type / Mode of delivery Uses Image 1. Depocyt : Pacira Pharmaceuticals Liposome Injection / Oral delivery Intrathecal treatment of lymphomatous meningitis. 2. Estrasorb : Graceway Pharmaceuticals Topical emulsion / Topical delivery Treatment of moderate to severe vasomotor symptoms due to menopause 3. Onivyde : Merrimack Pharmaceuticals Liposome injection / Intravenous delivery In combination with fluorouracil and leucovorin, for the treatment of metastatic adenocarcinoma of the pancreas
- 71. 4. Marqibo : Talon therapeutics Liposomal injection / intravenous infusion Acute lymphoblastic leukemia 5. Mepact : IDM Pharma Liposomal injection / intravenous infusion Treatment of high-grade resectable non- metastatic osteosarcoma 6. DaunoXome : Gilead Sciences Liposomal injection / intravenous infusion First line cytotoxic therapy for advanced HIV-associated Kaposi's sarcoma 7. Doxil : Ben Venue Laboratories Liposomal injection / intravenous infusion 1. Ovarian cancer 2. AIDS-related Kaposiās Sarcoma 3. Multiple Myeloma
- 72. Type Segment Analysis : 1.Nano Tubes 2.Nano Wires 3.Nano Shells 4.Quantum Dots 5.Nano Pros Applications Segment Analysis : 1.First Order Targeting (Organ Compartmentalization) 2.Second Order Targeting (Cellular Targeting) 3.Third Order Targeting (Intracellular Targeting)
- 75. The current focus in pharmaceuticals is shifting to a āsmart drugā paradigm, in which increased efficacy and decreased toxicity are the motivating factors. Rationally designed drug delivery system enables us to precisely control drug release rates for prolonged duration and sometimes help targeting the drugs such as anti cancer agents to specific body sites. Only in recent years, the idea of development of such systems became practical. In a short time, targeted drug delivery systems have had an impact on nearly every branch of medicine.
- 76. . THANK YOUā¦