Comparison of doxorubicin concentration profiles in radiofrequency-ablated rat livers from sustained- and dual-release plga millirods

Feng Qian, Nicholas Stowe, Gerald M. Saidel, Jinming Gao

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Purpose. To evaluate and compare the local pharmacokinetics of doxorubicin in radiofrequency (rf)-ablated rat livers after interstitial delivery from sustained- and dual-release poly(D,L-lactide-co-glycolide) (PLGA) millirods. Methods. PLGA millirods with sustained- and dual-release kinetics (burst followed by sustained release) of doxorubicin were implanted in rf-ablated rat livers. Doxorubicin release kinetics in vivo were measured from explanted millirods by UV-Vis spectrophotometer over 8 days. Spatial distribution of doxorubicin in liver tissues was measured by fluorescence imaging. Results. In the initial 24 h after millirod implantation, dual-release millirods released significantly more doxorubicin into liver tissues than the sustained millirods. Subsequently, both types of millirods provided comparable sustained-release kinetics over 8 days. With dual-release millirods, doxorubicin concentration and penetration distance in liver tissue increased more rapidly. To reach 30 μg/g doxorubicin concentration at the ablation boundary (targeted site of action), the time required was 6 days and 1.5 days for sustained- and dual-release millirods, respectively. Conclusions. Compared with sustained-release millirods, dual-release millirods provide a quick concentration elevation and sustaining of the drug concentration at the ablation boundary. Additionally, the steady-state drug concentration agrees well with model predictions based on previously determined transport parameters, which demonstrates the feasibility of rational design of drug formulations in polymer millirods.

Original languageEnglish (US)
Pages (from-to)394-399
Number of pages6
JournalPharmaceutical Research
Volume21
Issue number3
DOIs
StatePublished - Mar 1 2004

Keywords

  • Doxorubicin
  • Dual-release kinetics
  • Intratumoral drug delivery
  • Poly(D,L-lactide-co-glycolide)
  • Radiofrequency ablation

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Comparison of doxorubicin concentration profiles in radiofrequency-ablated rat livers from sustained- and dual-release plga millirods'. Together they form a unique fingerprint.

  • Cite this