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Accession Number ADA575578
Title Site-Directed Nanotherapeutics to Abrogate RRMS and Promote Remyelination Repair.
Publication Date Sep 2012
Media Count 15p
Personal Author D. Pearse M. Ghosh P. Dalton T. Fuehrmann
Abstract Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the human central nervous system. The clinical disease course is variable and starts with reversible episodes of neurological disability (remitting relapsing (RR-MS) stage). This transforms into a disease of continuous and irreversible neurological decline. Phosphodiesterase (PDE)-4/7 inhibitors can prevent injury-induced reductions of cAMP as well as facilitate tissue protection, anatomical repair, and functional recovery. PDE inhibitor containing nanoparticles (NP), surface modified with peptides that recognize proteins extravasated at sites of vascular disruption (clotting factors, ECM), can accumulate at regions of CNS demyelination, reducing tissue injury and promoting remyelination repair at very low drug doses. Characterization of non- functionalized polymeric (poly(ethylene glycol-b- -caprolactone)) NP demonstrated a size range of 28-42nm, no surface charge and a low polydispersity index. Size varied depending on amount of aminated PEG-b- PCL+peptide incorporated. NP allowed inclusion of fluorescent dyes (DiI, DiO) and the PDE-inhibitors Rolipram and BRL50481. Whereas the loading efficiency of the fluorescent dyes was high (approximately 45% and 80% respectively), drug loading was low in comparison, but could be improved by using more polymer. The drugs were released slowly over three weeks at 37C, after which NP started to aggregate/disassemble. Functionalization of the NP with peptides (i.e. NQEQVSP, DPEAAE and NIDPNAV) improved adherence in fibrin gels (blood clots) or tissue sections of the injured spinal cord (contusion type injury, explanted 1 week after injury).
Keywords Abrogates
Adhesion
Anatomy
Australia
Cardiovascular system
Clinical medicine
Coagulation
Demyelinating diseases
Diseases
Drug delivery
Drugs
Ethylene
Factor xiiia
Fibrin
Fibrin (Blood) clot
Fluorescent dyes
Foreign reports
Incapacitation
Indexes
Inhibitors
Irreversible processes
Laminin
Multiple sclerosis
Nanoparticles
Nerve fibers
Nervous system diseases
Neurology
Nidogen
Pde(Phosphodiesterase)
Peptides
Phosphodiesterase
Phosphodiesterase inhibitor
Polymers
Regions
Repair
Reversible
Rr-ms(Remitting-relapsing)
Sheaths(Anatomy)
Tenascin c
Tissues(Biology)
Versican
Wounds and injuries

 
Source Agency Non Paid ADAS
NTIS Subject Category 57E - Clinical Medicine
57W - Stress Physiology
Corporate Author Queensland Univ. of Technology, Brisbane (Australia).
Document Type Technical report
Title Note Final rept. 1 Sep 2010-30 Aug 2012.
NTIS Issue Number 1319
Contract Number W81XWH-10-1-0770

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