TY - JOUR
T1 - Modulating β-lapachone release from polymer millirods through cyclodextrin complexation
AU - Wang, Fangjing
AU - Blanco, Elvin
AU - Ai, Hua
AU - Boothman, David A.
AU - Gao, Jinming
N1 - Funding Information:
This work was supported by NIH grant CA90696 to JG and DOD grant W81XWH‐04‐1‐0164 to DAB. EB is grateful for the support of a National Institutes of Health minority supplement grant. This is report 002 from the Program in Cell Stress and Cancer Nanomedicine at UT Southwestern Medical Center at Dallas.
PY - 2006/10
Y1 - 2006/10
N2 - β-Lapachone (β-lap) is a novel anticancer agent that kills tumors overexpressing the NADP(H): quinone oxidoreductase enzyme. However, poor aqueous solubility and low bioavailability hinder its therapeutic applications. Herein we describe the development of poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods for local delivery of β-lap. The objective was to investigate the use of β-lap inclusion complexes with cyclodextrins (CDs) to control β-lap release kinetics from PLGA millirods. Differential scanning calorimetry was performed to measure drug/polymer interactions, complexation efficiency with different CDs, and complex/polymer interactions. β-Lap was found to have a solid-state solubility of 13% in PLGA. β-Lap dissolution in PLGA matrix lowered the glass transition temperature of PLGA from 44 to 31°C, and led to a slow release of β-lap (8.8 ± 1.2% release after 22 days). For β-lap and CD interactions, increasing complexation efficiency was observed in the order of α-CD, γ-CD, and β-CD, β-Lap complexation with hydroxypropyl-β-cyclodextrin (HPβ-CD) prevented drug dissolution in PLGA, and led to fast release (79.6 ± 2.1% after 2 days). Sustained drug release was achieved when β-lap was complexed with α-CD or γ-CD. These data demonstrate the ability to tailor β-lap release kinetics via CD complexation, providing exciting opportunities for the use of β-lap-millirods for intratumoral drug delivery.
AB - β-Lapachone (β-lap) is a novel anticancer agent that kills tumors overexpressing the NADP(H): quinone oxidoreductase enzyme. However, poor aqueous solubility and low bioavailability hinder its therapeutic applications. Herein we describe the development of poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods for local delivery of β-lap. The objective was to investigate the use of β-lap inclusion complexes with cyclodextrins (CDs) to control β-lap release kinetics from PLGA millirods. Differential scanning calorimetry was performed to measure drug/polymer interactions, complexation efficiency with different CDs, and complex/polymer interactions. β-Lap was found to have a solid-state solubility of 13% in PLGA. β-Lap dissolution in PLGA matrix lowered the glass transition temperature of PLGA from 44 to 31°C, and led to a slow release of β-lap (8.8 ± 1.2% release after 22 days). For β-lap and CD interactions, increasing complexation efficiency was observed in the order of α-CD, γ-CD, and β-CD, β-Lap complexation with hydroxypropyl-β-cyclodextrin (HPβ-CD) prevented drug dissolution in PLGA, and led to fast release (79.6 ± 2.1% after 2 days). Sustained drug release was achieved when β-lap was complexed with α-CD or γ-CD. These data demonstrate the ability to tailor β-lap release kinetics via CD complexation, providing exciting opportunities for the use of β-lap-millirods for intratumoral drug delivery.
KW - β-lapachone
KW - Cyclodextrin inclusion complexation
KW - Drug delivery
KW - Drug-polymer interactions
KW - Poly(lactic/glycolic) acid (PLGA)
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U2 - 10.1002/jps.20721
DO - 10.1002/jps.20721
M3 - Article
C2 - 16883563
AN - SCOPUS:33749996935
SN - 0022-3549
VL - 95
SP - 2309
EP - 2319
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 10
ER -