Degradex® plga   MICROSPHERES AND NANOPARTICLES

Degradex® Microspheres and Nanoparticles for Drug Delivery Research and Formulation Development

PLGA Microspheres and Nanoparticles: Degradex® Products by Phosphorex, Inc.

Biodegradable polymers such as poly(lactide-co-glycolide), PLGA, and polycaprolactone are widely used for biomedical and pharmaceutical applications. They have been used in clinical products approved by the US Food and Drug Administration (FDA).  PLGA degrades in the body by hydrolysis of its ester backbone into non-toxic products, which are either excreted by the kidneys or eliminated as CO2 and water through biochemical pathways.
Degradex® PLGA microspheres are polymeric particles in the size range of microns to millimeters. PLGA polymers have been used to encapsulate drug molecules. Drug loaded PLGA microspheres are used as long-acting, sustained release pharmaceutical formulations. There have been drug loaded PLGA microspheres in the market place. For example, Luprolide acetate microspheres are commercial products for the treatment of prostate cancer and endometriosis. Such “Depot” products can be subcutaneously administered at 1 month, 3 month or even 6 month intervals. When drug loaded PLGA microspheres are administered, the PLGA polymer starts to degrade in the body fluid and as it degrades the drug molecules are gradually released from the microspheres. The drug release rate can be modulated by the selection of the type of PLGA polymer and by adjusting the encapsulation process. For example, the following parameters can affect the drug release profile:
·         The ratio of lactide to glycolide, i.e. L/G ratio. PLGA polymers having an L/G ratio of 50/50 offers the fastest drug release.
·         The molecular weight or inherent viscosity of the PLGA polymer. The higher the MW, the more slowly the drug releases.
·         The end group of the PLGA polymer. Carboxyl terminated PLGA polymers offer faster drug release than ester end-capped ones.
Degradex® PLGA nanoparticles are PLGA particles under 1 micron. Phosphorex supplies these particles in the size range of from 50 nm to 1 micron. PLGA nanoparticles are good candidates for drug carriers enabling targeted drug delivery. Drug molecules can be encapsulated into the nanoparticles or conjugated onto the surface of the nanoparticles. These drug loaded PLGA nanoparticles (either encapsulated or surface coated) can be used in the following applications:
·         protect drugs from premature degradation;
·         target a specific site, e.g. tumor;
·         facilitate cell entry;
·         help cross blood-brain barrier;
·         increase solubility and bioavailability;
·         extend plasma circulation time. Typically this is done by using PEGylated PLGA nanoparticles.
In some cases, PLGA nanoparticle themselves can have therapeutic effects against certain diseases [2].
A variety of active pharmaceutical ingredients (API) may be encapsulated into PLGA microspheres and nanoparticles. They can be a small molecule or a macromolecular drug, water-soluble or poorly soluble. Examples of these API’s include small molecule drugs, peptides, proteins, DNA’s, RNA’s, oligonucleotides, antibodies, etc.
It needs to be noted that Degradex® PLGA microspheres and nanoparticles are plain PLGA particles not loaded with any API; however, these particles can be used in drug delivery research or product development as a control agent, or to test system compatibility before loading the drug.
All the Degradex® PLGA microspheres and nanoparticles are also available in the form of fluorescent particles. Such fluorescent particles can facilitate imaging in the drug delivery research.

References
1.       Cancer Vaccines: Material breach: An experimental vaccine implanted beneath the skin could usher in biomaterial-based immunotherapies for cancer.
Elie Dolgin 
Nature 504, S16-S17 (2013).
2.       Therapeutic Inflammatory Monocyte Modulation Using Immune-Modifying Microparticles
Getts, D., et al.
Science Translational Medicine 6, 219 (2014).   
3.       A humidity-sensitive hydrogel-Bacillus spore composite for micropatterning of biomolecular gradient
Richard L. Gieseck, Bin-Da Chan, Cagri Savran
Review of Scientific Instruments 84, (2013).
4.       Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis
Daniel R Getts, et al.
Nature Biotechnology 30, 1217–1224 (2012).
5.       Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations
Bonelli, Patrizia, et al.
Int. J. Nanomedicine 7, 5683–5691 (2012).
6.       Murine pulmonary inflammation model: a comparative study of anesthesia and instillation methods
Lacher, S., Johnson, C., Jessop, F., Holian, A., Migliaccio, C.  
Inhalation Toxicology 22(1), 77-83 (2010).
7.       Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly
Pham, N-L., Pewe, L., Fleenor, C., Langlois, R., Legge, K., Badovinac, V., & Harty, J.
PNAS 107(27), 12198–12203 (2010).
Degradex® is a registered trademark of Phosphorex, Inc.