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The Use of Nanoparticles in Drug Delivery Systems

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Title: The Use of Nanoparticles in Drug Delivery Systems


1
The Use of Nanoparticles in Drug Delivery Systems
  • Ali Palejwala

2
Overview
  • Introduction to the nanoparticles
  • Background on different types of nanoparticles

3
History
  • Have been documented to in use since the use 9th
    century in Mesopotamia for ancient pottery
  • Gold particles nanosclaed have optical properties
    that cause the luster

4
The Idea
  • Proposed by Richard Feynman in his book titled
    Theres Plenty of Room at the Bottom
  • Feynman considered the possibility of direct
    manipulation of individual atoms as a more
    powerful form of synthetic chemistry than those
    used at the time.
  • The idea of nanotechnology was born.

5
Current Trends in Nanomedicine
  • The majority of progress of nanomedicine has been
    in the use of nanoparticles as drug delivery
    products

6
What and Why
  • Nanoparticle any particle that is sized between
    1 and 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

7
Size and Shape
  • All matter has size and all size matters
  • General properties of nanoscaled particles
  • 1. High surface area to volume ratio
  • -able to interact with biomolecules on the
    surface of cells
  • -absorbs drugs well
  • 2. Able to diffuse through the body well

8
Types of Nanoparticles
  • Liposomes
  • Polymeric nanoparticles
  • Dendrimers
  • Fullerenes
  • Quantum dots
  • Metal nanoparticles
  • Magnetic nanoparticles

9
Liposomes
  • a self-closing spherical particle that is
    composed of natural or synthetic amphiphilic
    lipid molecules

10
One can change the pharmacokinetic properties of
the drug by changing the liposome
  • Size smaller liposomes have reduced
    immunogenicity
  • Lipid composition give the membrane varied
    rigidity
  • Stealth component reduces the immunogenicity
  • The drug enclosed

11
  • Liposomes have been widely used in anticancer
    drugs
  • Optimal antitumor activity occurs when cancer
    cells are exposed to moderate concentrations of a
    drug over an extended period of time

12
  • http//www.chemocare.com/managing/

13
Doxil
  • Developed in 1995
  • Marketed by Ortho Biotech
  • Liposome-PEG doxorubicin HCl
  • Anti-cancer drug used
  • in the treatment of HIV-related Kaposis sarcoma
  • Also used to treat breast cancer, ovarian cancer,
    and other solid tumors
  • Administered intravenously every 4 weeks

14
  • 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 diastearoylphospatidylch
    oline and cholesterol - increases liposomal
    rigidity

15
  • 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

16
Side effects
  • Hand-Foot Syndome
  • Stomatitis
  • Fever
  • Neutropenia
  • Nausea, vomiting, tiredness, weakness, rash,
    shortness of breath, or mild hair loss
  • Loss of appetite
  • Diarrhea
  • Cardiotoxcity

17
DepoCyt
  • Approved by the FDA in 2004
  • Marketed by SkyePharma
  • Liposomal cytarabine
  • Anticancer drug used in the treatment of
    malignant neoplastic meningitis
  • Administered intravenously every 2 weeks

18
Neoplastic Meningitis
  • A common oncologic complication involving the
    spread of tumor cells to the subarachnoid space
    (SAS)
  • Cancer cells in the subarachnoid space can
  • Settle in the dependent portions of the base of
    brain (cranial nerves, lower spinal canal)
  • grow into the surface of the brain and fill the
    sulci
  • block normal paths of CSF flow
  • Treatment options include chemotherapy and/or
    radiation

19
Cytarabine
  • Originally discovered in Europe in the
  • 1960s
  • works by damaging the DNA in
  • cancerous cells
  • Short half-life in the body requires
  • frequent dosage to attain cytotoxic levels
  • Clinical studies demonstrated that
  • encapsulation of cytarabine into
  • liposomes leads to sustained release of
    cytotoxic cytarabine
  • - improved therapeutic efficacy in patients with
    NM

20
Depofoam
  • Lipid composition mainly dioleoyl
    phospahtidylcholine, triolein, and cholesterol
  • Depofoam results in a 55 fold increase in the
    terminal half life of cytarabine in the CSF
  • Composed of multiple monoclonal antibodies to
    target cancer cells
  • Larger liposome high drug loading capacity
    small enough to cross the blood brain barrier

21
Other Liposomal Drugs
22
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23
Liposomes and Antibiotics
  • Drug targeting potential of liposomes and
    nanoparticles in the treatment of intracellular
    bacterial infections.
  • Poor penetration into cells and decreased
    activity intracellularly major reasons for
    limited activity of most antibiotics in
    intracellular infections.

24
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25
Polymeric Nanoparticles
  • Nanoparticles synthesized from polymers

26
The polymer can act as the active
ingredientCopaxone
  • Approved by the FDA in 1996 for the treatment of
    multiple sclerosis (T-cell therapy)
  • Synthetic polymer of amino amino acids (Cop1
    composed of L-Ala, L-Lys, L-Glu, and L- Tyr)
  • Administered subcutaneously
  • Marketed by TEVA pharmaceuticals

27
Multiple Sclerosis
28
Polymer Synthesis
  • Initiator n-carboxyamino acid anhydride
  • Growth reaction with amino acid
  • monomers
  • Termination reaction with n-carboxyamino
  • acid anhydride
  • Length can be controlled by monomer/initiator
    ratio
  • As long as the composition of polymer is the
    same, the physical and chemical properties will
    stay same (regardless of sequence)

29
Mechanism of Action
  • Cop 1 polymer related to myelin binding protein
    (MBP)
  • Binding to MHC leads to the activation of
    T-suppressor cells
  • Competes with several myelin-associated antigens
    to bind to MHC class II molecules
  • Low toxicity however, copaxone can only slow the
    progression of the disease and reduce the relapse
    rate

30
Side effects
  • Flu-like symptoms
  • injection site rxns
  • menstrual irregularities
  • decreased white blood cells
  • elevated liver enzymes.

31
The polymer can be conjugated to a drugPegasys
  • Approved by the FDA in 2005 protein therapeutic
    for the treatment of Hepatitis B, C
  • covalent conjugate of recombinant alfa-2a
    interferon with a single branched bis-monomethoxy
    polyethylene glycol (PEG) chain
  • Administered through subcutaneous injection

32
  • PEG can enhance plasma stability and solubility
    of the drug while reducing its immunogenicity
  • The protein therapeutic will have an increased
    amount of time to act on the virus
  • Pegasys is often used with Ribavirin in the
    treatment of hepatitis C

33
Side effects
  • decompensated cirrhosis
  • autoimmune hepatitis
  • major, uncontrolled depression
  • kidney, lung or heart transplants
  • known hypersensitivity (allergic reaction) to
    pegylated interferon components. Pegylated
    interferon should be used with caution,
    preferably by a specialist, in people with heart
    and thyroid problems, pulmonary disorders, and
    autoimmune diseases.

34
The polymer can resemble a liposome
  • How?

Amphiphilic polymer
35
  • Polymer has specific responses that depend on the
    stimulus and the environment
  • - in an aqueous environment, the polymer will
    aggregate into a micelle
  • - upon binding to glucose, the compound
    experiences a change in pka that dissociates the
    polymer

36
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

37
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38
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39
Dendrimer
  • Highly branched, spherical nanoparticle
  • Core, highly branched layers of repeating units
    (polymers), and multiple active terminal groups

40
Pros and Cons
  • High level of activity as a result of multiple
    functional groups at surface display strong
    surface activity with cell and virus particle
    surfaces
  • limited information concerning physicochemical
    properties
  • Tough to synthesize

41
Toxicity
42
Conclusion
  • The development of particles that are nanoscaled
    has created great opportunities in the
    development of improved drug delivery systems.

43
Works Cited
  • http//www.eperc.mcw.edu/fastFact/ff_135.htm
  • ?http//www.sciencedirect.com/
  • ?http//www.weizmann.ac.il/ICS/booklet/1/pdf/copax
    on.pdf
  • ?http//www.rxlist.com/pegasys-drug.htm
  • http//www.rsc.org/delivery/_ArticleLinking/Displa
    yArticleForFree.cfm?doib900374fJournalCodeCC
  • http//www.unisa.edu.au/iwri/futurestudents/phdpro
    jects/interfacialpropertiesofdendrimers.asp
  • Zhang, L. "Nanoparticles in Medicine."
    Translational Medicine.
  • Patel, Priyal. "Nanotechnology." Drug Delivery
    Technology.
  • Patel, Priyal. Nanoparticles in cancer research
    a novel drug deliverypharmacologicalapproach
    Drug Delivery Technology.
  • Murry, R.Clinicalpharmacology of encapsulated
    sustained-release cytarabine The Annals of
    pharmacotherapy.
  • Massing, U.Cancertherapy with liposomal
    formulations of anticancer drugs. International
    journal of clinical pharmacology, therapy, and
    toxicology.
  • Hashimoto, N. An approach to cancer chemotherapy
    by application of monoclonal antibody-modified
    liposomesInternational congress series.
    International congress series.
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