Modulating β‐lapachone release from polymer millirods through cyclodextrin complexation

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.