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dendrimer a wonderful tool for drug delivery dendrimer a wonderful tool for drug delivery Presentation Transcript

  • Dendrimers a wonderful tool foranti-cancerous drug delivery systemYashvant Raoraoyash6@gmail.comCentre for NanosciencesCentral University of GujaratGandhinagar INDIA
  • Outline Dendrimers Properties of dendrimers Biocompatibility of dendrimers Dendrimers as drug delivery foranti-cancerous drug
  • What are dendrimers ??????• Dendrimer is a nanoparticle and has many advantagesover micro particles or others due to its small size, easyuptake by cells. (through endocytosis)• Dendrimers are branched macromolecules have a centralcore unit having a high degree of molecular uniformity,narrow molecular weight, distribution, specific size and shapecharacteristics, and a highly- functionalized, terminal surface.The manufacturing process is a series of repetitive stepsgenerating shells starting with a central initiator core.
  • Dendrimers can be define three different regions: core, branchesand surface. They are an ideal scaffold to assemble a greatnumber of functional units in a volume of nanometric dimensionwith a precise control on the nature, position, and distance of thevarious groups. Moreover, thanks to their three-dimensional structure,they possess dynamic cavities in which small ions or molecules can behosted.
  • Properties ofDendrimersProperties DenrimersStructure Compact and GlobularSynthesis Careful and stepwisegrowthStructural control Very highShape SphericalCrystallinitty Non-crystalline,amorphous materials,lower glass temperatureAqueous solubility HighNon polar solubility HighViscosity Non linear relationshipwith molecular weightReactivity High
  • Biocompatibility of DendrimersAccumulation of low MW dendrimers is not usually aproblem due to excretion in the urine or in feces after metabolism.Injected polymers of high MW are not easily execrated if they can notto be degrade or filtered via the kidney.To be useful in the biological system, Denderimer must beNon toxicNon immunogenicAble to stay in circulation for the time needed to have a clinical effectAble to cross bio barrier (i.e. intestine, blood tissue barrier, cell membrane)Able to target specific structures.
  • Dendrimers as a drug deliveryDendrimers are ideal for drug delivery because theyEnhance the aqueous solubilityIncrease circulation half lifeTarget certain tissuesImprove transit across biological barrierSlow drug metabolismDendrimers as gene transfer agents because theyUnmodified PAMAM and PPI dendrimers can form complexeswith DNAPartially degraded or fragmented (activated ) dendrimers helptransfection efficiency.Slight excess of primary amines is beneficial
  • DRUG DELIVRYSCAFFOLD Highly branched dendrimers, depicted here amongcells shown in green, may one day deliver drug molecules surely
  • Cont………………Cationic dendrimers with covalently attached drugs are used to deliverhigh concentrations of drug close to a cell surface (extra cellular matrixtargeted local drug delivery)Cell specific drug delivery folic acid derivatized dendrimers (folate receptors are over expressed incancer cells) Methotrexate (MTX) for treatment.
  • PAMAM dendrimer as anti-cancerous drug carrier:partially modified surface with acyl groupsfolate as a targeting Ligandsfluorescein or radio labeledabout 9 wt% methotrexateIntravenous administration to mice with subcutaneous tumorRESULTSConcentration of dendrimer in tumor was 5 to 10 times greater than controllacking folate.Methotrexate conjugated to dendrimer had significantly lower toxicity and 10-foldhigher efficiency than free methotrxate at an equivalent cumulative dose.15 bi-weekly injections of compound showed a significant decrease in the rateof tumor growth.Reference: Kukowska-latallo, at al. cancer res. 2005, 65, 5317
  • CONCLUSIONDendrimers are extremely well-defined, globular, synthetic macromoleculesWith characteristics that make them useful for numerous biological application .Dendrimers are manufactured in high purities with few structural defects.Easily characterized by standard methods (MS, IR, SEC, HPLC, NMR etc.)Several dendrimers are commercially available as drug carriers, membranepermeability and targeting diagnostic markers and biosensors.
  • ACKNOWLEDGEMENTProf. Man Singh,Dean school of chemical sciences,Central university of Gujarat INDIAProf. V. Elangovan,H.O.D. Dept. of applied animal sciences,Babasaheb Bhimrao Ambedkar Central UniversityLucknow INDIAProf. G. Sunil Babu,Prof. Dept. of Biotechnology,Babsaheb Bhimrao Ambedkar Central UniversityLucknow INDIA