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The use of submicron/nanoscale PLGA implants to deliver paclitaxel with enhanced pharmacokinetics and therapeutic efficacy in intracranial glioblastoma in mice

Paper ID Volume ID Publish Year Pages File Format Full-Text
8383 588 2010 9 PDF Available
Title
The use of submicron/nanoscale PLGA implants to deliver paclitaxel with enhanced pharmacokinetics and therapeutic efficacy in intracranial glioblastoma in mice
Abstract

Pharmacokinetics and therapeutic efficacy of submicron/nanoscale, intracranial implants were evaluated for treating malignant glioblastoma in mice. 9.1% (w/w) paclitaxel-loaded polylactide-co-glycolide (PLGA) nanofiber discs (F3) were fabricated and characterized for morphology and size distribution. Along with F3, three other formulations, 9.1% (w/w) paclitaxel-loaded PLGA submicron-fiber discs (F2), 16.7% (w/w) paclitaxel-loaded PLGA microspheres entrapped in hydrogel matrices (H80 and M80) were intracranially implanted in BALB/c mice and the coronal brain sections were analyzed for bio-distribution of paclitaxel on 14, 28 and 42 days post-implantation. BALB/c nude mice with intracranial human glioblastoma (U87 MG-luc2) were used in the therapeutic efficacy study. Animals were randomized to intracranial implantation of F3 and H80 with paclitaxel dose of 10 mg/kg, placebo F3, placebo H80, weekly intratumoral injection of Taxol® (10 mg/kg) or no treatment and the treatment response was analyzed by bioluminescence imaging and histological (H&E, Ki-67) examinations. Enhanced, therapeutic paclitaxel penetration (∼1 μm) in the mouse brain up to 5 mm from the implant site even after 42 days post-implantation from F3 and H80 was confirmed and deduced to be diffusion/elimination controlled. F3 and H80 demonstrated significant (∼30 fold) tumor inhibition and significantly low tumor proliferation index after 41 days of treatment in comparison to sham and placebo controls. The submicron/nanoscale implants are able to demonstrate optimal paclitaxel pharmacokinetics in the brain/tumor with significant tumor inhibition in a glioblastoma xenograft model in mice and hence could be potentially useful to treat highly recurrent GBM.

Keywords
Glioblastoma; Paclitaxel; Chemotherapy; Submicron/nanoscale; Polymers
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The use of submicron/nanoscale PLGA implants to deliver paclitaxel with enhanced pharmacokinetics and therapeutic efficacy in intracranial glioblastoma in mice
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 19, July 2010, Pages 5199–5207
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us