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Polymeric Nano-Systems Used in Drug Delivery

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Title: Polymeric Nano-Systems Used in Drug Delivery


1
Polymeric Nano-Systems Used in Drug Delivery
  • Arsen Simonyan
  • SUNY-ESF

2
Types of Nano-Sized Drug Delivery Vehicles
  • Nanosuspensions Nanocrystals
  • Liposomes
  • Solid Lipid Nanoparticles
  • Nanotubes Nanowires
  • Polymeric Nanoparticles

3
Benefits of Polymer Systems
  • Increase stability of volatile drug agents
  • Produced relatively easily
  • Vast source of chemistries available
  • May have engineered specificity both to the drug
    and the target difficult to achieve with other
    carriers
  • Drug-release profiles and triggering dependent on
    polymer structure

4
Qualities of Relevant Polymers
  • Biodegradable/Biocompatible lactic acid,
    glycolic acid, ethylene glycol, glycerin, fatty
    acids, amino acids, sugars, etc.
  • Structure mostly copolymers, combining
    different qualities of their parent polymers
    Tg, Tm, crystal structure, or exhibiting new ones
    - self-assembly

random
graft
alternating
block
5
Most Common Types of Block Copolymers
  • Typical Applications as
  • - Micro and nano-particles
  • (mPEO-PLA, PLA)
  • Unimolecular drug vehicles
  • (star blocks PEG-PLA, PLA-PEG, dendr-PBE-PEO,
    etc.)
  • Hydrogels (Pluronics, PEO-PBO, PEG-PLGA,
    dendr-PBE-PEO, PIPAAm-PAA, PEO-PLA)
  • Micellar systems (PEG-PLys, PEG-PAsp,
    PIPAAm-PBMA,etc.)
  • Surface modifications
  • Drug conjugates

AB diblock
ABA triblock or ABC
Multiblock
n
Star block
6
Nano-particles
  • Benefits
  • - Fairly easy preparation
  • Good control over size and size distribution
  • Good protection of the encapsulated drug
  • Longer clearance times
  • Drawbacks
  • Extensive use of poly(vinyl alcohol)-PVA as
  • a detergent - issues with toxicity
  • - Limited targeting abilities

PLA nanoparticles loaded with HAS formed by a
double emulsion technique, stabilized with PVA
Image taken from M. F. Zambauxa, F. Bonneauxa, ,
R. Grefb, P. Maincentc, E. Dellacherieb, M. J.
Alonsod, P. Labrudea and C. Vignerona, J.
Controlled Release, 1998, 50, 31
7
Star Block Copolymers
  • Benefits
  • Smaller sizes and lower intrinsic viscosities
    leading to better excretion
  • Size determined by chemical structure and
    uniform size distribution
  • Long clearance times due to slow degradation
  • Possibility for attachment of homing (targeting)
    device at the extremities
  • of the arms
  • Drawbacks
  • Smaller loading capacity per molecule
  • - Longer preparation and purification process

Image taken from Youxin Li, Thomas Kissel,
Polymer, 1998, 39, 4421
8
Hydrogels
  • Benefits
  • - Closest analogue to living tissue
  • - Capable of binding large amounts of fluids and
    drugs, incl. proteins
  • - Swelling ratio controllable by variation in
    structure (mostly by the hydrophobic/hydrophilic
    ratio)
  • - Small changes in temperature, pH,
    electric/magnetic field can trigger
  • large volume change/release of drug
  • In many cases well defined release patterns -
    t1/2
  • Drawbacks
  • - More difficult to characterize/predict behavior
  • - Not as well defined as stoichiometric compounds

9
Micellar Systems
  • Benefits
  • - Unique core-shell structure
  • - Fairly high loading capacities depending on the
    chemistry of the drug
  • - Attachment of homing device(s) possible
    biotin, folic acid, antibodies
  • - Variation of polymer composition, free charges,
    hydrophobic/
  • hydrophilic ratio, offers vast possibilities
    for design of unique
  • gene/protein/drug delivery vehicles
  • - Physical affinity targeting using
    stimuli-responsive polymers to pH,
    electro-magnetic fields, temperature
  • - Additional crosslinking in the core/shell leads
    to
  • novel nanostructures with different drug delivery
    properties

10
Crosslinkable micelles
Drawbacks - Difficult prediction of micellar
characteristics by unimer structure - Not very
well studied
Image taken from Roesler, A., Vandermeulen, W,
Klok, H., Adv. Drug Deliv. Rev., 2001, 53, 95
11
Surface Modification and Drug Conjugation,
Examples
1
3
2
Images 12 taken from Roesler, A., Vandermeulen,
W, Klok, H., Adv. Drug Deliv. Rev., 2001, 53,
95 Image 3 taken from Anil K. Patri, Jolanta F.
Kukowska-Latallo, James R. Baker Jr., Adv. Drug
Deliv. Rev., 2005, 57/15
12
Conclusions
  • Polymeric systems have great potential in drug
    delivery applications
  • Offer closest mimicking of natural products
  • Difficult characterization, expensive and long
    processes of synthesis and purification are major
    drawbacks
  • Still none of the discussed systems is applied in
    practice to patients FDA approval requires
    extensive toxicity investigations
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