Targeted drug delivery system

Targeted drug delivery system, drug carriers, niosomes, nanoparticles, etc

1. Presented By: Mahewash Sana A. Pathan TARGETED DRUG DELIVERY SYSTEM

2. TARGETED DRUG DELIVERY SYSTEM Def: “Targeted drug delivery is an advanced method of delivering drugs to the patients in such a targeted sequence that increases the concentration of delivered drug to the targeted body part of interest only (organs/tissues/cells) which in turn improves efficacy of treatment by reducing side effects of drug administration ”. Targeted drug research began in the 1970s, its main form is for injection, with the development, the current trend of drug delivery system, drug research and development is the use of liposome, lipid, protein, fat, microspheres and biodegradable polymers as drug carrier. Targeted drugs originally is mainly used in cancer treatment, to maximize the efficacy of a drug is of prime importance during the choice of the delivery system. 2

3. IDEAL CHARACTERS Targeted drug delivery systems should be biochemically inert (non-toxic ) should be non-immunogenic should be physically and chemically stable in vivo and in vitro conditions should have restricted drug distribution to target cells or tissues or organs should have uniform capillary distribution should have controllable and predictable rate of drug release drug release should not affect the drug action should have therapeutic amount of drug release should have minimal drug leakage during transit 3

4. TYPES OF TARGETED DRUG DELIVERY 4

5. 1. Passive targeting It refers to the accumulation of drug or drug carrier system at a specific site. The drugs are targeted to systemic circulation. Targeting is occurring because of the body’s natural response to physicochemical characters of drug. Examples include targeting of antimalarial drugs for treatment of leishmiansis , brucellosis, and candidiasis. 5

6. 2. Active targeting Active targeting means a specific ligand – receptor type interaction for intracellular localization which occurs only after blood circulation and extravasations. This active targeting approach can be further classified into three different levels of targeting which are: a) First order targeting refers to restricted distribution of the drug carrier systems to the capillary bed of a predetermined target site, organ or tissue e.g. compartmental targeting in lymphatic, peritoneal cavity, plural cavity, cerebral ventricles and eyes, joints. b) Second order targeting refers to selective delivery of drugs to specific cell types such as tumour cells and not to the normal cells e.g. selective drug delivery to kupffer cells in the liver. c) Third order targeting refers to drug delivery specifically to the intracellular site of targeted cells e.g. receptor based ligand mediated entry of a drug complex into a cell by endocytosis . 6

7. 3. Inverse targeting This approach leads to saturation of RES and suppression of defense mechanism by pre-injecting large amount of blank colloidal carriers. This is an effective approach for non-RES organs. 7

8. 4. Dual targeting The carrier molecule itself has their own therapeutic activity and therefore increases effect of drug 8

9. 5. Double targeting In this type the temporal and spatial methodologies are combined to target a carrier system. 9

10. 6. Combination targeting similar to double targeting, the combination targeting systems for the site specific delivery of proteins and peptides are equipped with molecular specificity. The latter provides a direct access to the target site. 10

11. COMPONENTS OF DRUG TARGETING Target: Target means an organ or a tissue or a cell, which is in need of treatment. 2 . Drug Carrier or Marker: Drug delivery is possible only by means of a carrier system. Carriers are molecules or any other systems responsible for the successful transportation of a drug to the site of interest. Carriers are vectors specifically engineered for the purpose of holding a drug inside them. This is possible by means of encapsulation. 11

12. DRUG DELIVERY VEHICLES These transport the drug either within or in the vicinity of target. An ideal drug delivery vehicle is supposed to cross even stubborn sites such as a blood brain barrier. It should be easily recognized by the target cells and the drug- ligand complex hence formed should be stable. These need to be non-toxic, biodegradable as well. The biodegradable nature of drug carrier enables them to be easily cleared away by the body and physiological mechanism, and thus avoids any chance of their accumulation within cells that may lead to cytotoxicity. 12

13. Liposome : Liposomes are small artificial vesicles of spherical shape that can be created from cholesterol and natural nontoxic phospholipids. Due to their size and hydrophobic and hydrophilic character (besides biocompatibility), liposomes are promising systems for drug delivery . Carbon Materials: Nanoscale carbon materials usually including carbon nanotubes97, graphene98 / graphene-oxide99, and nano diamond Targeting and selectivity during cancer cell destruction has also been reported through molecular surface functionalization of single-walled carbon nanotubes (SWCNTs) both in vitro and in vivo. It usually has a diameter between 10 nm and 1000 nm. The drug is usually made from natural polymer material and has been fully applied to treatment course of tumor, diabetes and vascular disease. It can effectively extend action time of drug, then effectively improve clinical effect of the drug and minimize toxic and side effects of the drug. Compare with other materials, Carbon can be much cheaper, but the chirality and diameter of nanotubes, which severely impact the physical and chemical properties, they are difficult to control. 13

14. 3 . Metallic nanomaterials: Metallic nanomaterials including gold and silver nanocrystals and nano rods have been shown to generate localized hyper thermal heating through the absorption of incident optical radiation and surface Plasmon relaxation to treat the disease. Its advantage is low cost, easily synthesized nanoparticles and the particles are also having a high thermal stability. PEG-DSPE coating may be related to better absorption, based on the stability and a pharmacokinetic improvement in the blood circulation time. This method will lead to enhanced permeation for nanoparticles to across the vascular endothelium and achieve improved accumulation in the tumor . 4. Iron oxide nanocrystals : The difference between the magnetic particles and their metallic and semiconducting counterparts is the mechanism by which the particle is heated. Briefly, magnetic hyperthermia is achieved by applying external alternating magnetic fields to cause the magnetic particles to heat through hysteresis loss ( Néel relaxation) or induced eddy currents. 14

15. 5. Nano micelles: Polymeric Nano micelles are formed by amphiphilic polymers with distinct hydrophobic and hydrophilic segments. The polymer self-assembles to form micelles in aqueous solution. The mechanism of drug release from Nano micelles is dependent on the nature and strength of interactions between core-forming polymer and drug molecules, micelle stability. 6. Carbon nanotubes: Carbon nanotubes (CNT) have recently been studied as novel and versatile drug and gene delivery vehicles. When CNT are suitably functionalized, they can interact with various cell types and are taken up by endocytosis . Some anti-cancer drugs cisplatin , methotrexate , the antifungal compound amphotericin B and doxorubicin have been delivered by these. Shorter multi-walled CNTs (MWCNTs, i.e., 1 μm) have been reported to penetrate the cell membrane more efficiently than the longer CNTs, which can inhibit their uptake by self-arranging into a coiled or bundled shape. Different types of nucleic acids such as micro-RNA ( miRNA ), small-interfering (siRNA) and plasmid DNA ( pDNA ) can be bound to CNTs and transferred into mammalian cells. Oral administration of peptides has problems with enzymatic degradation and poor uptake from the gut, but CNTs were proposed to overcome these limitations. 15

16. 7. Mesoporous silica materials: Mesoporous silica nanoparticles (MSNPs) is uniformly sized, porous and dispersible nanoparticles using colloidal chemistry and evaporation-induced self-assembly. This kind of material enables the loading of diverse cargos and cargo combinations at levels exceeding those of other common drug delivery carriers such as liposomes or polymer conjugates. 8. Noisome: Noisome are non-ionic surfactant vesicles obtained on hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or other lipids. They are vesicular systems similar to liposomes that can be used as carriers of amphiphilic and lipophilic drugs . 9. Lymphocytes : They act as a source of macromolecule particularly DNA for other cells. 16

17. 10. Microspheres and microcapsules: Microencapsulation is a process in which solids. Liquids and gases are enveloped in a membrane that may be impermeable or semi impermeable. Microspheres and microcapsules differ from the reservoir system. Targeting of these is based on the fact that the capillary of human body are in microns. So one can easily target the capillaries of lung, blood, liver, etc. 11. Neutrophils : These are an attractive carrier system for the transport of diagnostic or therapeutic agents to acute inflammation. They can be highly purified to contain carrier proteins within their granules and are designed to accumulate in large number at area of pathology . 12. Fibroblasts: They are used as a source of lysosomal enzymes. These are advantageous in replacement therapy because no surgery is needed for the recipient 17

18. 13. Artificial cells: These cells envelopes smaller spherical membrane system which contain different enzyme systems. This is useful for sequential type of compartmentalization. These cells can be used for any type of material which needs to be microencapsulated by interfacial polymerization technique. 15. Nanoerythrosomes : These are the derivative of erythrocyte ghosts. Nanoerythrocytes are vesicles prepared by extrusion, sonication or electric breakdown of RBC, the average diameter of these vescicles are 0.1 to 0.2 nm. 16. Resealed erythrocytes: Carrier erythrocytes have many attributes of ideal carrier. Since the patient’s own erythrocytes may be used, these are no danger of adverse effects from foreign net negative charge due largely to hydroxyl group of sialic acid . 17. Lymphocytes : These cells acts as a source of macromolecules particularly DNA for other cells . 18

19. 18. Ufasomes : Unsaturated fatty acid vesicles ( ufosomes ) are suspensions of closed lipid bilayer that are composed of fatty acids, and their ionized species (soaps) which are restricted to narrow pH range from 7 to 9. 19. Neutrophils : A neutrophil is a type of WBC, a type of granulocyte, and a type of phagocyte. These are a type of immune cell that is one of the first cell types to travel to the site of an infection. These are attractive carrier systems for the transport of diagnostic and therapeutic agents to areas of acute inflammation. 20. Pharmacosomes: Pharmacosomes may be defined as a neutral molecule possessing both positive and negative charge, water loving and fat loving properties, and an optimum ratio of polyphenol with phospholipids in a complex form. The drug is present in a dispersion form in these lipoidal DDS conjugated by electron pair sharing and electrostatic forces or by forming a hydrogen bond with lipids . 19

20. 21. Virosome: Virosomes are consist of spherical or unilamellar phospholipids bilayer vescicle having mean diameter in the range of 120-180 nm. Influenza virus is most commonly used for virosome production and genetic material of the source virus. Virosomes are biodegradable, non-poisonous and non-auto immunogenic. They enable medication conveyance into the cytoplasm of target cells. 23. Proteosome : The proteosome is a large protein complex responsible for degradation of intracellular proteins, a process that requires metabolic energy. Proteosome proteins are highly hydrophobic and their protein-protein interaction causes them to form multimolecular membrane vescicles . 24. Cubosome: Cubosomes are distinct, sub-micron, nano-shaped particles of bicontinuous cubic liquid crystalline stages. Mostly cubosomes are prepared by polymers, lipids and surfactants with polar and nonpolar constituents hence said to be amphiphilic. These are suitable for injections . 20

21. 25. Monoclonal antibodies: These are the antibodies that are made by identical immune cells that are clones of unique parent cell. These are highly specific and recognize only antigenic determinants or receptor site. MABs coupled with an active drug hold great promises for site specific delivery of drug, particularly in cancer chemotherapy. 26. Resealed erythrocytes: The drug loaded carrier erythrocytes are prepared by collecting blood samples from the organism of interest, separating them from plasma, entrapping drug in the erythrocytes, and resealing the resultant cellular carriers hence these carriers are called as resealed erythrocytes. Upon reinjection the drug loaded erythrocytes serve as slow circulating depots and target the drug to reticuloendothelial system (RES). 27. Quantum dots: A quantum dot is a semiconductor nanostructure that confines the motion of conduction band electrons, valence band holes or bound pairs of conduction band electrons and valence band holes in all three spatial directions. The ability to tune the size of quantum dots is advantageous for many applications and it is one of the most promising candidates as vehicle for drug transportation with it’s in solid-state quantum computation used for diagnosis, drug delivery, Tissue engineering, catalysis, filtration and textiles technologies too . 21

22. 28. Prodrug: Prodrugs have also been called latentiated drugs, bio-reversible derivatives and congeners. Usually prodrug implies a covalent link between a drug and chemical moiety, although some times this term is used to characterize some salt of active drug. These approaches are not only very useful in decreasing side effects but also increase/decrease solubility as required, lipophilicity, mask taste and enhance bioavailability. A more advanced version of prodrug is chemical delivery system (CDS) in which drug is transformed into an inactive derivative which involve a cascade of enzymatic reaction for activation. 22

23. CONCLUSION Delivery of drug molecule to reach its specific site is itself a difficult task in the complex cellular network of an organism. The term drug targeting implies to the drug delivery which exist for localizing a therapeutic agent on the minority of cells that are actually in need of treatment. Nano delivery systems hold great potential to overcome some of the obstacles to efficiently target a number of diverse cell types . This represents an exciting possibility to overcome problems of drug resistance in target cells and to facilitate the movement of drugs across barriers (e.g., BBB). Research related to the development of targeted drug delivery system is now a day is highly preferred and facilitating field of pharmaceutical world. 23

24. REFERENCES: Bae YH, Park K. Targeted drug delivery to tumors: myths, reality and possibility. Journal of Controlled Release, vol. 153, 2011. Gupta M, Sharma V. Targeted drug delivery system: A review. Research Journal of Chemical Sciences, vol. 1, 2011. Agnihotri J, Saraf S, Khale A. Targeting: new potential carriers for targeted drug delivery system. International Journal of Pharmaceutical Sciences Review and Research, vol. 8, 2004. K. Rani and S. Paliwal , A review on targeted drug delivery: Its entire focus on advanced therapeutics and diagnostics, Scholars Journals of Applied Medical Sciences, 2014. R. Singh and J.W. Lillard Jr., Nanoparticle-based targeted drug delivery, ExpMolPathol , vol.86, 2009. A. Pandey et al ., Targeted drug delivery (site specific drug delivery), Journal of Scientific and Industrial research, vol. 63, 2004. N. Mishra et al ., Targeted Drug Delivery: A Review, American Journal of PharmTech Research 2016. J. Gautami , Targeted Drug delivery systems, Research and Reviews: Journal of Pharmaceutics and Nanotechnology, vol.3, 2015. Akbarzadeh et al ., Liposome: classification, preparation, and applications, Nanoscale Research Letters 2013. Madhava NVS et al ., Niosomes : A Novel Drug Delivery System, International Journal of Research in Pharmacy and Chemistry, 2011. R. Deepika B. et al., Resealed Erythrocyte Drug Delivery: A Review, International Journal of research in Pharmacy and Chemistry, 2013. 24

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