Design and development of pH-responsive polyurethane membranes for intravaginal release of nanomedicines

Design and development of pH-responsive polyurethane membranes for intravaginal release of nanomedicines
김수현Seungil KimYannick Leandre TraoreEmmanuel A. HoMuhammad ShafiqSong Liu
Issue Date
Acta Biomaterialia
VOL 82-23
The objective of this study was to develop and characterize a novel intravaginal membrane platform for pH-triggered release of nanoparticles (NPs), which is essential for efficient intravaginal delivery of certain effective but acid-labile therapeutic agents for sexually transmitted infections, such as small interfering RNA (siRNA). A pH-responsive polyurethane (PU) was electrospun into a porous nanofibrous membrane. The diameters of the fibers, as well as the thickness and pore sizes of the membrane under dry and wet conditions (pH 4.5 and 7.0), were determined from scanning electron microscopy (SEM) micrographs. pH-dependent zeta-potential (ζ) of the membrane was evaluated using a SurPASS electrokinetic analyzer. Visiblex™ color-dyed polystyrene NPs (PSNs, 200  nm, COOH) and CCR5 siRNA-encapsulated solid lipid NPs (SLNs) were used for in vitro NP release studies in a vaginal fluid simulant (VFS) at pH 4.5 (normal physiological vaginal pH) and 7.0 (vaginal pH neutralization by semen). During 24  h of incubation in VFS, close-to-zero PSNs (2  ±  1%) and 28  4% SLNs were released through the PU membrane at pH 4.5, whereas the release of PSNs and SLNs significantly increased to 60  6% and 59  8% at pH 7.0, respectively. The pH-responsive release of NPs hinged on the electrostatic interaction between the pH-responsive membrane and the anionic NPs, and the change in pH-responsive morphology of the membrane. In vitro biocompatibility studies of the membrane showed no significant cytotoxicity to VK2/E6E7 human epithelial cells and Sup-T1 human T-cells and no significant changes in the expression of pro-inflammatory cytokines (IL-6, IL-8, and IL-1β). Overall, the porous pH-responsive PU membrane demonstrated its potential in serving as a “window” membrane in reservoir-type intravaginal rings (IVRs) for pH-responsive intravaginal release of NPs.
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