NDLI: Biodegradable intraprostatic doxorubicin implants

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The AAPS Journal : Volume 9, Issue 1, March 2007

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Biodegradable intraprostatic doxorubicin implants

Content Provider	Springer Nature Link
Author	Ortiz, Ronnie Au, Jessie L S. Lu, Ze Gan, Yuebo Wientjes, M. Guillaume
Copyright Year	2007
Abstract	Systemic chemotherapy is not effective in the treatment of prostate-confined cancer. We developed biodegradable, doxorubicin-loaded cylinders for intraprostatic implantation and evaluated the feasibility of using regional intraprostatic drug therapy to treat prostate-confined cancer. Cylinders were prepared using poly(lactide-co-glycolide) (PLG) or PLG copolymers. The in vitro and in vivo drug release, intraprostatic pharmacokinetics, and histopathology in dogs implanted with the cylinders were studied. The doxorubicin-loaded cylinders made of PLG polymers of 7.9 to 54 kDa molecular weight (MW) had a diameter of ∼800 μm, drug loading of 10% to 30% (wt/wt), and even distribution of crystalline drug throughout the matrix. Burst release varied from 3% to 73%, and 7-day cumulative release from 4% to 90%. Decreasing polymer MW and increasing drug loading were associated with higher initial burst release and overall release rates. The in vivo drug release from cylinders (33-kDa PLG, 30% drug loading) in dog prostates was rapid (∼80% in 48 hours). Spatial drug distribution, visualized using confocal fluorescence microscopy, showed high concentrations confined to the lobule containing the implant (referred to as the implanted lobule), with steep concentration gradients over the septa separating the lobules. Concentrations in the implanted lobule were about 8 times higher than concentrations delivered by an intravenous injection. The implants caused necrotic cell death in the implanted lobule, without damage to prostatic nerve bundles or the urethra. These results indicate the feasibility of using biodegradable PLG cylinders as intraprostatic implants to selectively deliver high drug concentrations to prostate tissue.
Starting Page	E241
Ending Page	E250
File Format	PDF
ISSN	12341234
Journal	The AAPS Journal
Volume Number	9
Issue Number	2
e-ISSN	15507416
Language	English
Publisher	Springer-Verlag
Publisher Date	2007-01-01
Publisher Institution	American Association of Pharmaceutical Scientists
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	PLG doxorubicin prostate delivery controlled release biodegradable implants Pharmacy Pharmacology/Toxicology Biotechnology
Content Type	Text
Resource Type	Article

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