4.2 Article

Thyrotropin-Releasing Hormone Loaded and Chitosan Engineered Polymeric Nanoparticles: Towards Effective Delivery of Neuropeptides

Journal

JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
Volume 16, Issue 5, Pages 5324-5332

Publisher

AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jnn.2016.12431

Keywords

Polymeric Nanoparticles; Thyrotropin-Releasing Hormone; Poly(lactide-co-glycolide) PLGA; Chitosan; Neuropeptides; Nanoformulation

Funding

  1. Science Education and Research Board (SERB) of India [SB/SO/BB/0040/2013]
  2. University Grants Commision (UGC), India [20-10 (12)/2012]
  3. Department of Biotechnology (DBT), India [BT/10460PFN/20/871/2013]
  4. Council of Scientific and Industrial Research (CSIR), India
  5. UGC, India

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Thyrotropin-Releasing Hormone (TRH), a tripeptide amide with molecular formula L-pGlu-L-His-L-Pro-NH2, is used in the treatment of brain/spinal injury and certain central nervous system (CNS) disorders, including schizophrenia, Alzheimer's disease, epilepsy, depression, shock and ischemia due to its profound effects on the CNS. However, TRH's therapeutic activity is severely hampered because of instability and hydrophilicity owing to its peptidic nature which results into ineffective penetration into the blood brain barrier. In the present study, we report the synthesis and stability studies of novel chitosan engineered TRH encapsulated poly(lactide-co-glycolide) (PLGA) based nanoformulation. The aim of such an encapsulation is to allow effective delivery of TRH in biological systems as the peptidase degrade naked TRH. The synthesis of TRH was carried out manually in solution phase followed by its encapsulation using PLGA to form polymeric nanoparticles (NPs) via nanoprecipitation technique. Different parameters such as type of organic phase, concentration of stabilizer, ratio of organic phase and aqueous phase, rate of addition of organic phase were optimized, tested and evaluated for particle size, encapsulation efficiency, and stability of NPs. The TRH-PLGA NPs were then surface modified with chitosan to achieve positive surface charge rendering them potential membrane penetrating agents. PLGA, PLGA-TRH, Chitosan-PLGA and Chitosan-PLGA-TRH NPs were characterized and analyzed using Dynamic Light Scattering (DLS), Transmissiom Electron Microscopy (TEM) and Infra-red spectroscopic techniques.

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