To provi
de better protection for wo
men against sexually trans
mitte
d infections, on-
de
man
d intravaginal
drug
delivery was atte
mpte
d by synthesizing reversibly
pH-sensitive polyether-polyurethane copoly
mers using poly(ethylene glycol) (PEG) an
d 1,4-bis(2-hy
droxyethyl)piperazine (HEP). Che
mical structure an
d ther
mo-characteristics of the synthesize
d polyurethanes were confir
me
d by attenuate
d total reflectance-Fourier transfor
m infrare
d spectroscopy (ATR-FTIR),
1H-nuclear
magnetic resonance (
1H-NMR), an
d melting point testing. Me
mbranes were cast by solvent evaporation
metho
d using the prepare
d pH-sensitive polyurethanes. The i
mpact of varying pH on
me
mbrane swelling an
d surface
mor
phology was evaluate
d via swelling ratio change an
d scanning electron
microscopy (SEM). The prepare
d pH-responsive
me
mbranes showe
d two ti
mes higher swelling ratio at pH 4 than pH 7 an
d pH-triggere
d switchable surface
mor
phology change
m>.m> The anionic anti-infla
mmatory
drug
diclofenac so
diu
m (NaDF) was use
d as a
mo
del co
mpoun
d for release stu
dies. The prepare
d pH-responsive polyurethane
me
mbranes allowe
d continuous NaDF release for 24 h an
d aroun
d 20% release of total NaDF within 3 h at pH 7 but little-to-no
drug release at pH 4.5. NaDF per
meation across the prepare
d me
mbranes
de
monstrate
d a reversible pH-responsiveness. The pH-responsive polyurethane
me
mbranes
di
d not show any noticeable negative i
mpact on vaginal epithelial cell viability or in
duction of pro-infla
mmatory cytokine pro
duction co
mpare
d to controls. Overall, the non-cytotoxic HEP-base
d pH-responsive polyurethane
de
monstrate
d its potential to be use
d in
me
mbrane-base
d i
mplants such as intravaginal rings to achieve on-
de
man
d &l
dquo;on-an
d-off&r
dquo; intravaginal
drug
delivery.
d="absSec_2">Statement of Significance
d="sp0015">A reversible and sharp switch between “off” and “on” drug release is achieved for the first time through new pH-sensitive polyurethane membranes, which can serve as window membranes in reservoir-type intravaginal rings for on-demand drug delivery to prevent sexually transmitted infections (STIs). Close to zero drug release occurs at the normal vaginal pH (4.5) for minimal side effects. Drug release is only triggered by elevation of pH to 7 during heterosexual intercourse. The reversibly sharp and fast “on-and-off” switch arises from the creative incorporation of a pH-sensitive monomer in the soft segment of polyurethane. This polyurethane biomaterial holds great potential to better protect women who are generally at higher risk and are more vulnerable to STIs.