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Radiolabeling and Tumour Targeting Applications of Surface–Modified Solid Lipid Nanoparticles by Using Octreotide Analogues

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Title Radiolabeling and Tumour Targeting Applications of Surface–Modified Solid Lipid Nanoparticles by Using Octreotide Analogues
 
Creator Banerjee, Indranil
 
Subject Infectious Diseases and Immunology
 
Description 99mTc-paclitaxel was synthesized by using sodium borohydride as a reducing agent.Greater than 95 % labelling efficiency was achieved. Radiochemical purity of the synthesized 99mTc-paclitaxel was validated by Thin Layer Chromatography (TLC) scanner and High
Performance Liquid Chromatography (HPLC). 99mTc-paclitaxel passed in vitro stability tests.
Biodistribution and scintigraphy studies were performed in Sprague-Dawley rats. The biodistribution study results of 99mTc-paclitaxel were related mainly to the metabolism
and excretion routes followed by the parental drug, paclitaxel (PTX). Apart from that,biodistribution of 99mTc-paclitaxel was altered after pre-treatment with cold PTX. Hence,99mTc-paclitaxel may be used as a tracer for PTX.Nanoparticle biodistribution study is of great importance in bringing nanomedicine to patients. Solid lipid nanoparticle (SLN) with dimension less than 100 nm was successfully radiolabelled with 99mTc by using sodium borohydride as a reducing agent (instead of stannous salts). PTX was used as a model anticancer drug for the preparation of drug loaded SLN (PSLN). PSLN was characterized by standard methods. Encapsulation efficiency for PTX in PSLN was estimated by HPLC. Taxol formulation and PSLN were radiolabelled separately and subsequent characterizations of these complexes were performed. Greater than 95% radiolabelling efficiency was achieved and the labelling efficiency was calculated to be more than 90% up to 24 h. Interference of radiocolloids on the biodistribution can be avoided
by this method as both the radiolabelling efficiency and radiochemical purity of the complex was found to be > 95%. Radiolabelling by this method was found to be easy and effective. 99mTc-PSLN and 99mTc-Taxol passed the in vitro stability tests. 99mTc-PSLN achieved more
brain concentration than 99mTc-Taxol as determined by biodistribution studies. This study indicates prepared PSLN may effectively deliver more PTX in brain than the marketed formulation of PTX (i.e. Taxol). Apart from that, this type of radiolabelling technique can be
useful in preclinical evaluation of drug loaded SLN.
PSLN improved the apoptosis-induction activity of PTX in C6 rat glioma cell line (as compared to Taxol). SPECT imaging and biodistribution studies showed that 99mTc-PSLN has achieved considerable concentration within the orthotopic glioma-bearing rats. More importantly, PSLN exhibited powerful antitumor activity without observable accompanied toxicity. Survival experiment further confirmed the improved anti-glioma efficacy of PSLN.
 
Date 2015
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2632/1/Indranil_Banerejee_Thesis.pdf
Banerjee, Indranil (2015) Radiolabeling and Tumour Targeting Applications of Surface–Modified Solid Lipid Nanoparticles by Using Octreotide Analogues. PhD thesis, J U.
 
Relation http://www.eprints.iicb.res.in/2632/