title: Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery.
abstract: Leucine-enkephalin (Leu-Enk) is a neurotransmitter or neuromodulator in pain transmission. Due to non-addictive opioid analgesic activity of this peptide, it might have great potential in pain management. Leu-Enk loaded N-trimethyl chitosan (TMC) nanoparticles were prepared and evaluated as a brain delivery vehicle via nasal route. TMC biopolymer was synthesized and analyzed by (1)H NMR spectroscopy. TMC nanoparticles were prepared by ionic gelation method. Mean peptide encapsulation efficiency and loading capacity were 78.28±3.8% and 14±1.3%, respectively. Mean particle size, polydispersity index and zeta potential were found to be 443±23 nm, 0.317±0.17 and +15±2 mV respectively for optimized formulations. Apparent permeability coefficient (Papp) of Leu-Enk released from nanoparticles across the porcine nasal mucosa was determined to be 7.45±0.30×10(-6) cm s(-1). Permeability of Leu-Enk released from nanoparticles was 35 fold improved from the nasal mucosa as compared to Leu-Enk solution. Fluorescent microscopy of brain sections of mice showed higher accumulation of fluorescent marker NBD-F labelled Leu-Enk, when administered nasally by TMC nanoparticles, while low brain uptake of marker solution was observed. Furthermore, enhancement in brain uptake resulted into significant improvement in the observed antinociceptive effect of Leu-Enk as evidenced by hot plate and acetic acid induced writhing assay.
authors.affiliation: SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur (CG) 495009, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Ravi Shankar
authors.initials: RS
authors.lastname: Pandey
authors.forename: Kartik Chandra
authors.initials: KC
authors.lastname: Patra
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Jain
authors.forename: Muarai Lal
authors.initials: ML
authors.lastname: Soni
authors.forename: Jawahar Singh
authors.initials: JS
authors.lastname: Dangi
authors.forename: Jitender
authors.initials: J
authors.lastname: Madan
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004743:Enkephalin, Leucine / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D009666:Nose / Q000187:drug effects*; D010539:Permeability; D013552:Swine
chemical_list: D004337:Drug Carriers; C118071:N-trimethyl chitosan chloride; D009479:Neuropeptides; D004743:Enkephalin, Leucine; D048271:Chitosan
keywords: Antinociceptive; Brain delivery; Enkephalin; Trimethyl chitosan