To provi
de better protection for wo
men a
gainst sexually trans
mitte
d infections, on-
de
man
d intrava
ginal
dru
g delivery was atte
mpte
d by synthesizin
g reversibly
pH-sensitive polyether-polyurethane copoly
mers usin
g 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
ma
gnetic resonance (
1H-NMR), an
d meltin
g point testin
g. Me
mbranes were cast by solvent evaporation
metho
d usin
g the prepare
d pH-sensitive polyurethanes. The i
mpact of varyin
g pH on
me
mbrane swellin
g an
d surface
mor
pholo
gy was evaluate
d via swellin
g ratio chan
ge an
d scannin
g electron
microscopy (SEM). The prepare
d pH-responsive
me
mbranes showe
d two ti
mes hi
gher swellin
g ratio at pH 4 than pH 7 an
d pH-tri
ggere
d switchable surface
mor
pholo
gy chan
ge
m>.m> The anionic anti-infla
mmatory
dru
g 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
dru
g 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 ne
gative i
mpact on va
ginal 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 intrava
ginal rin
gs to achieve on-
de
man
d &l
dquo;on-an
d-off&r
dquo; intrava
ginal
dru
g 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.