To provi
de better prote
ction for women against sexually transmitte
d infe
ctions, on-
deman
d intravaginal
drug
delivery was attempte
d by synthesizing reversibly
pH-sensitive polyether-polyurethane
copolymers using poly(ethylene gly
col) (PEG) an
d 1,4-bis(2-hy
droxyethyl)piperazine (HEP). Chemi
cal stru
cture an
d thermo-
chara
cteristi
cs of the synthesize
d polyurethanes were
confirme
d by attenuate
d total refle
ctan
ce-Fourier transform infrare
d spe
ctros
copy (ATR-FTIR),
1H-nu
clear magneti
c resonan
ce (
1H-NMR), an
d melting point testing. Membranes were
cast by solvent evaporation metho
d using the prepare
d pH-sensitive polyurethanes. The impa
ct of varying pH on membrane swelling an
d surfa
ce mor
phology was evaluate
d via swelling ratio
change an
d s
canning ele
ctron mi
cros
copy (SEM). The prepare
d pH-responsive membranes showe
d two times higher swelling ratio at pH 4 than pH 7 an
d pH-triggere
d swit
chable surfa
ce mor
phology
change
. The anioni
c anti-inflammatory
drug
di
clofena
c so
dium (NaDF) was use
d as a mo
del
compoun
d for release stu
dies. The prepare
d pH-responsive polyurethane membranes 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 permeation a
cross the prepare
d membranes
demonstrate
d a reversible pH-responsiveness. The pH-responsive polyurethane membranes
di
d not show any noti
ceable negative impa
ct on vaginal epithelial
cell viability or in
du
ction of pro-inflammatory
cytokine pro
du
ction
compare
d to
controls. Overall, the non-
cytotoxi
c HEP-base
d pH-responsive polyurethane
demonstrate
d its potential to be use
d in membrane-base
d implants su
ch as intravaginal rings to a
chieve on-
deman
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.