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Posted: May 15, 2006

Controlled drug delivery systems in neurodegenerative diseases

(Nanowerk Spotlight) It still is a huge challenge to treat neurodegenerative diseases such as Alzheimer, Parkinson or Huntington, which are increasingly affecting our society as the average life-span of our population increases. One of the main obstacles for successful therapy of these disorders is safe and effective drug delivery to the central nervous system.
Although several compounds that exhibit a therapeutic effect in experimental models of neuro-degenerative diseases have been identified over recent years, their safe and effective delivery to the central nevous system remains a challenge. Since the central nervous system is protected by the blood-brain barrier (BBB), many substances that circulate in blood, for instance drugs, do not have access to the brain.
One of the possible ways to resolve this problem was recently pointed out by Natalija Popovic and Patrik Brundin from the Wallenberg Neuroscience Center at Lund University in Sweden in their mini-review "Therapeutic potential of controlled drug delivery systems in neurodegenerative disease", published in the May 18, 2006 issue of International Journal of Pharmaceutics.
The authors explained to Nanowerk that, based on experimental studies in animal models of Parkinsonís, Alzheimerís and Huntingtonís diseases, two alternative procedures for treatment of these diseases in humans could be achieved:
a) implantation of drug-containing biodegradable devices like microparticles, microspheres, and nanoparticles, or
b) transplantation of nonbiodegradable capsules that accommodate cells that synthesize and release deficient trophic factors, hormones or neurotransmitters.
"These delivery devices, usually made from synthetic polymers (i.e. poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and poly(lactic-co-glycolic acid) (PLGA)) are well tolerated by the host tissue and do not exhibit cytotoxic, immunologic, carcinogenic or teratogenic effects even after chronic exposure" says Popovic. "The rate of biodegradation varies from less than one month to a few years."
According to the researchers, the application of these procedures is still limited due to the practical problems that fall within at least four different areas:
  • Loading capacity and abilities for controlled and sustained release of active agent
  • Drug instability and particle degradation
  • Drug penetrability and
  • Safety of the implantation procedure.
  • Further improvement of polymeric drug delivery systems will require that a larger volume of brain parenchyma is selectively targeted. Popovic and Brundin conclude that the focus of research should be on development of devices with sustained, controlled and self-regulated drug release.
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