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