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Meticulous Doxorubicin Release from pH‐Responsive Nanoparticles Entrapped within an Injectable Thermoresponsive Depot
Author(s) -
Yu Huayang,
Ingram Nicola,
Rowley Jason V.,
Green David C.,
Thornton Paul D.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202000389
Subject(s) - doxorubicin , ethylene glycol , methacrylate , nanoparticle , aqueous solution , chemistry , drug delivery , polymer chemistry , controlled release , polymer , drug carrier , nuclear chemistry , materials science , organic chemistry , copolymer , nanotechnology , chemotherapy , medicine , surgery
Abstract The dual stimuli‐controlled release of doxorubicin from gel‐embedded nanoparticles is reported. Non‐cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)‐ b ‐poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH‐responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin‐loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin‐loaded nanoparticles could be incorporated within a thermoresponsive poly(2‐hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2‐hydroxypropyl methacrylate) in dimethyl sulfoxide solution into aqueous solution. The combination of the poly(2‐hydroxypropyl methacrylate) gel and poly(ethylene glycol)‐ b ‐poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near‐complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in non‐acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site‐specific release of chemotherapeutics.