To provi
de better protection for women against sexually transmitte
d infections, on-
deman
d intravaginal
drug
delivery was attempte
d by synthesizing reversibly
pH-sensitive polyether-polyurethane copolymers using poly(ethylene glycol) (PEG) an
d 1,4-bis(2-hy
droxyethyl)piperazine (HEP). Chemical structure an
d thermo-characteristics of the synthesize
d polyurethanes were confirme
d by attenuate
d total reflectance-Fourier transform infrare
d spectroscopy (ATR-FTIR),
1H-nuclear magnetic resonance (
1H-NMR), an
d melting point testing. Membranes were cast by solvent evaporation metho
d using the prepare
d pH-sensitive polyurethanes. The impact of varying pH on membrane swelling an
d surface mor
phology was evaluate
d via swelling ratio change an
d scanning electron microscopy (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 switchable surface mor
phology change
. The anionic anti-inflammatory
drug
diclofenac 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 across the prepare
d membranes
demonstrate
d a reversible pH-responsiveness. The pH-responsive polyurethane membranes
di
d not show any noticeable negative impact on vaginal epithelial cell viability or in
duction of pro-inflammatory cytokine pro
duction compare
d to controls. Overall, the non-cytotoxic HEP-base
d pH-responsive polyurethane
demonstrate
d its potential to be use
d in membrane-base
d implants such as intravaginal rings to achieve 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.