Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery

被引:81
作者
Kumar, Manoj [1 ]
Pandey, Ravi Shankar [1 ]
Patra, Kartik Chandra [1 ]
Jain, Sunil Kumar [1 ]
Soni, Muarai Lal [1 ]
Dangi, Jawahar Singh [1 ]
Madan, Jitender [2 ]
机构
[1] Guru Ghasidas Vishwavidyalaya, SLT Inst Pharmaceut Sci, Bilaspur 495009, CG, India
[2] Chandigarh Coll Pharm, Mohali 140307, PB, India
关键词
Enkephalin; Brain delivery; Trimethyl chitosan; Antinociceptive; HUMAN GROWTH-HORMONE; IN-VIVO EVALUATION; NASAL DELIVERY; DRUG-DELIVERY; ABSORPTION; ENKEPHALIN; CHLORIDE; VITRO; DERIVATIVES; PEPTIDES;
D O I
10.1016/j.ijbiomac.2013.06.041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 H-1 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 (P-app) of Leu-Enk released from nanoparticles across the porcine nasal mucosa was determined to be 7.45 +/- 0.30 x 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. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:189 / 195
页数:7
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