To provide better protection
for women
ag
ainst sexu
ally tr
ansmitted in
fections, on-dem
and intr
av
agin
al drug delivery w
as
attempted by synthesizing reversibly
pH-sensitive polyether-polyureth
ane copolymers using poly(ethylene glycol) (PEG)
and 1,4-bis(2-hydroxyethyl)piper
azine (HEP). Chemic
al structure
and thermo-ch
ar
acteristics o
f the synthesized polyureth
anes were con
firmed by
attenu
ated tot
al re
flect
ance-Fourier tr
ans
form in
fr
ared spectroscopy (ATR-FTIR),
1H-nucle
ar m
agnetic reson
ance (
1H-NMR),
and melting point testing. Membr
anes were c
ast by solvent ev
apor
ation method using the prep
ared pH-sensitive polyureth
anes. The imp
act o
f v
arying pH on membr
ane swelling
and sur
face mor
phology w
as ev
alu
ated vi
a swelling r
atio ch
ange
and sc
anning electron microscopy (SEM). The prep
ared pH-responsive membr
anes showed two times higher swelling r
atio
at pH 4 th
an pH 7
and pH-triggered switch
able sur
face mor
phology ch
ange
. The
anionic
anti-in
fl
amm
atory drug diclo
fen
ac sodium (N
aDF) w
as used
as
a model compound
for rele
ase studies. The prep
ared pH-responsive polyureth
ane membr
anes
allowed continuous N
aDF rele
ase
for 24 h
and
around 20% rele
ase o
f tot
al N
aDF within 3 h
at pH 7 but little-to-no drug rele
ase
at pH 4.5. N
aDF perme
ation
across the prep
ared membr
anes demonstr
ated
a reversible pH-responsiveness. The pH-responsive polyureth
ane membr
anes did not show
any notice
able neg
ative imp
act on v
agin
al epitheli
al cell vi
ability or induction o
f pro-in
fl
amm
atory cytokine production comp
ared to controls. Over
all, the non-cytotoxic HEP-b
ased pH-responsive polyureth
ane demonstr
ated its potenti
al to be used in membr
ane-b
ased impl
ants such
as intr
av
agin
al rings to
achieve on-dem
and “on-
and-o
ff” intr
av
agin
al drug delivery.
absSec_2">Statement of Significance
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.