Polymeric Nano-Systems Used in Drug Delivery

1
Polymeric Nano-Systems Used in Drug Delivery

• Arsen Simonyan
• SUNY-ESF

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Types of Nano-Sized Drug Delivery Vehicles

• Nanosuspensions Nanocrystals
• Liposomes
• Solid Lipid Nanoparticles
• Nanotubes Nanowires
• Polymeric Nanoparticles

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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

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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
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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
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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
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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

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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

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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
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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
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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