Combined modeling and experimental approach for the development of dual-release polymer millirods

Feng Qian, Gerald M. Saidel, Damon M. Sutton, Agata Exner, Jinming Gao

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

This paper describes a combined modeling and experimental approach for the design and development of a polymer device to provide local drug therapy to thermally ablated solid tumors. The polymer device, in the shape of cylindrical millirod, will be implanted via image-guided procedures into the center of the ablated tumor. Drug released from the millirod aims to eliminate residual cancer cells at the boundary of the normal and ablated tissue following thermal ablation to provide an effective treatment of the total tumor volume. The design of the millirod release kinetics is based on a mathematical model of drug transport in the ablated tumor and the surrounding normal tissue. The optimal release kinetics consists of a dual-release process - a burst release followed by sustained release - to provide the most optimal drug pharmacokinetics at the ablation boundary. Model analysis leads to a quantitative correlation of burst dose and release rates to the ablation size and the drug concentration at the ablation boundary. A three-layer polymer millirod is produced by a dip-coating method, and in vitro study demonstrates the dual-release kinetics in which a burst release occurs within 2 h followed by a sustained release over 7 -10 days. Independent control of the burst and sustained release rates is achieved by varying the structural composition of the outer and middle layers of the millirods, respectively. Results from this study provide the rational basis and experimental feasibility of dual-release millirods for further efficacy studies in solid tumors.

Original languageEnglish (US)
Pages (from-to)427-435
Number of pages9
JournalJournal of Controlled Release
Volume83
Issue number3
DOIs
StatePublished - Oct 30 2002

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Polymers
Pharmaceutical Preparations
Neoplasms
Equipment and Supplies
Residual Neoplasm
Tumor Burden
Research Design
Theoretical Models
Pharmacokinetics
Hot Temperature
Drug Therapy
Therapeutics

Keywords

  • Biodegradable polymer
  • Drug transport
  • Dual-release kinetics
  • Intratumoral drug delivery
  • Mathematical model
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Combined modeling and experimental approach for the development of dual-release polymer millirods. / Qian, Feng; Saidel, Gerald M.; Sutton, Damon M.; Exner, Agata; Gao, Jinming.

In: Journal of Controlled Release, Vol. 83, No. 3, 30.10.2002, p. 427-435.

Research output: Contribution to journalArticle

Qian, Feng ; Saidel, Gerald M. ; Sutton, Damon M. ; Exner, Agata ; Gao, Jinming. / Combined modeling and experimental approach for the development of dual-release polymer millirods. In: Journal of Controlled Release. 2002 ; Vol. 83, No. 3. pp. 427-435.
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