To prov
ide better protect
ion for women aga
inst sexually transm
itte
d infect
ions, on-
deman
d intravag
inal
drug
del
ivery was attempte
d by synthes
iz
ing revers
ibly
pH-sens
it
ive polyether-polyurethane copolymers us
ing poly(ethylene glycol) (PEG) an
d 1,4-b
is(2-hy
droxyethyl)p
iperaz
ine (HEP). Chem
ical structure an
d thermo-character
ist
ics of the synthes
ize
d polyurethanes were conf
irme
d by attenuate
d total reflectance-Four
ier transform
infrare
d spectroscopy (ATR-FTIR),
1H-nuclear magnet
ic resonance (
1H-NMR), an
d melt
ing po
int test
ing. Membranes were cast by solvent evaporat
ion metho
d us
ing the prepare
d pH-sens
it
ive polyurethanes. The
impact of vary
ing pH on membrane swell
ing an
d surface mor
phology was evaluate
d v
ia swell
ing rat
io change an
d scann
ing electron m
icroscopy (SEM). The prepare
d pH-respons
ive membranes showe
d two t
imes h
igher swell
ing rat
io at pH 4 than pH 7 an
d pH-tr
iggere
d sw
itchable surface mor
phology change
. The an
ion
ic ant
i-
inflammatory
drug
diclofenac so
dium (NaDF) was use
d as a mo
del compoun
d for release stu
dies. The prepare
d pH-respons
ive polyurethane membranes allowe
d cont
inuous NaDF release for 24 h an
d aroun
d 20% release of total NaDF w
ith
in 3 h at pH 7 but l
ittle-to-no
drug release at pH 4.5. NaDF permeat
ion across the prepare
d membranes
demonstrate
d a revers
ible pH-respons
iveness. The pH-respons
ive polyurethane membranes
did not show any not
iceable negat
ive
impact on vag
inal ep
ithel
ial cell v
iab
il
ity or
in
duct
ion of pro-
inflammatory cytok
ine pro
duct
ion compare
d to controls. Overall, the non-cytotox
ic HEP-base
d pH-respons
ive polyurethane
demonstrate
d its potent
ial to be use
d in membrane-base
d implants such as
intravag
inal r
ings to ach
ieve on-
deman
d &l
dquo;on-an
d-off&r
dquo;
intravag
inal
drug
del
ivery.
id="absSec_2">Statement of Significance
id="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.