polymeric nano-systems used in drug delivery arsen simonyan suny-esf
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Polymeric Nano-Systems Used in Drug Delivery
Arsen Simonyan
SUNY-ESF
Types of Nano-Sized Drug Delivery Vehicles
Nanosuspensions & Nanocrystals
Liposomes
Solid Lipid Nanoparticles
Nanotubes & Nanowires
Polymeric Nanoparticles
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
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
alternating
block
graft
Most Common Types of Block Copolymers
n
AB diblock
ABA triblockor ABC
Multiblock
Star block
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
Nano-particles
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
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
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
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
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 tonovel nanostructures with different drug delivery properties
Crosslinkable micelles
Image taken from Roesler, A., Vandermeulen, W, Klok, H., Adv. Drug Deliv. Rev., 2001, 53, 95
Drawbacks- Difficult prediction of micellar characteristics by unimer structure- Not very well studied
Surface Modification and Drug Conjugation, Examples
Images 1&2 taken from Roesler, A., Vandermeulen, W, Klok, H., Adv. Drug Deliv. Rev., 2001, 53, 95Image 3 taken from Anil K. Patri, Jolanta F. Kukowska-Latallo, James R. Baker Jr., Adv. Drug Deliv. Rev., 2005, 57/15
1
2
3
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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