TY - JOUR
T1 - Temperature-triggered on-demand drug release enabled by hydrogen-bonded multilayers of block copolymer micelles
AU - Zhu, Zhichen
AU - Gao, Ning
AU - Wang, Hongjun
AU - Sukhishvili, Svetlana A.
PY - 2013
Y1 - 2013
N2 - We report on hydrogen-bonded layer-by-layer (LbL) films as a robust, reusable platform for temperature-triggered "on-demand" release of drugs. Films with high drug loading capacity, temperature-controlled on-off drug release, and stability at physiological conditions were enabled by assembly of tannic acid (TA) with temperature-responsive block copolymer micelles (BCMs), which were pre-formed by heating solutions of a neutral diblock copolymer, poly(N-vinylpyrrolidone)-b-poly(N-isopropylacrylamide) (PVPON-b-PNIPAM), to a temperature above the lower critical solution temperature (LCST) of PNIPAM. The BCM/TA films exhibited temperature-triggered swelling/deswelling transitions at physiological conditions (swelling ratios of 1.75 and 1.2 at 37 °C and 20 °C, respectively). A model drug, doxorubicin (DOX) was incorporated into the film at a high drug-to-matrix ratio (∼9.3 wt.% of DOX per film mass), with a total loading capacity controlled by the film thickness. At 37 °C, DOX was efficiently retained within the hydrophobic BCM cores of BCM/TA films, whereas exposure to a lower temperature (20 °C) triggered fast DOX release. While neither bare BCM-containing films nor films loaded with DOX showed cytotoxicity at 37 °C, drug released from films at lower temperature exhibited high potency against breast cancer cells. Repeated on/off drug release was demonstrated with 1.5-um-thick DOX-loaded films, allowing at least three 30-min cooling cycles with consistent DOX (∼12-16% of loaded DOX released for each cycle) released over a 4-day period. Despite significant stress associated with multiple swelling/deswelling cycles, films maintained their structural integrity in PBS, and each film could be repeatedly loaded with drug and used more than 15 times with only ∼ 7% loss in film thickness and no obvious changes in reloading capacity or release profiles. This work presents the first proof-of-concept utility of temperature-responsive BCM-containing films for repeated on-demand release of a drug.
AB - We report on hydrogen-bonded layer-by-layer (LbL) films as a robust, reusable platform for temperature-triggered "on-demand" release of drugs. Films with high drug loading capacity, temperature-controlled on-off drug release, and stability at physiological conditions were enabled by assembly of tannic acid (TA) with temperature-responsive block copolymer micelles (BCMs), which were pre-formed by heating solutions of a neutral diblock copolymer, poly(N-vinylpyrrolidone)-b-poly(N-isopropylacrylamide) (PVPON-b-PNIPAM), to a temperature above the lower critical solution temperature (LCST) of PNIPAM. The BCM/TA films exhibited temperature-triggered swelling/deswelling transitions at physiological conditions (swelling ratios of 1.75 and 1.2 at 37 °C and 20 °C, respectively). A model drug, doxorubicin (DOX) was incorporated into the film at a high drug-to-matrix ratio (∼9.3 wt.% of DOX per film mass), with a total loading capacity controlled by the film thickness. At 37 °C, DOX was efficiently retained within the hydrophobic BCM cores of BCM/TA films, whereas exposure to a lower temperature (20 °C) triggered fast DOX release. While neither bare BCM-containing films nor films loaded with DOX showed cytotoxicity at 37 °C, drug released from films at lower temperature exhibited high potency against breast cancer cells. Repeated on/off drug release was demonstrated with 1.5-um-thick DOX-loaded films, allowing at least three 30-min cooling cycles with consistent DOX (∼12-16% of loaded DOX released for each cycle) released over a 4-day period. Despite significant stress associated with multiple swelling/deswelling cycles, films maintained their structural integrity in PBS, and each film could be repeatedly loaded with drug and used more than 15 times with only ∼ 7% loss in film thickness and no obvious changes in reloading capacity or release profiles. This work presents the first proof-of-concept utility of temperature-responsive BCM-containing films for repeated on-demand release of a drug.
KW - Block copolymer micelles
KW - Drug release
KW - Layer-by-layer
KW - Poly(N-isopropylacrylamide)
KW - Temperature responsive
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U2 - 10.1016/j.jconrel.2013.06.031
DO - 10.1016/j.jconrel.2013.06.031
M3 - Article
C2 - 23831052
AN - SCOPUS:84880893184
SN - 0168-3659
VL - 171
SP - 73
EP - 80
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -