SMART Polymer Fibers For Tampon-Like Nonsteroidal Contraceptive Devices

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PROJECT SUMMARY/ABSTRACT Natural fertility requires spermatozoa to migrate through viscoelastic secretions and to overcome the physiolog- ical acidic environment of the female reproductive tract. Our preliminary data show that novel mucoadhesive, bioresponsive polymer compositions maintain a physiologically acidic pH environment upon exposure to seminal fluid and, at the same time, dramatically increase viscoelastic properties, which negatively impacts sperm motil- ity. Therefore, it is hypothesized that - upon exposure to semen - the novel mucoadhesive, bioresponsive com- position rapidly transforms the vaginal cavity into an inhospitable environment for sperm. We propose to explore an innovative approach to on-demand non-steroidal contraception for women using SMART (= System Mute until Activation by a Remote Trigger) polymer fibers that maintain a physiological, protective vag- inal environment upon exposure to seminal fluid resulting in infertility. This high-risk/high-reward research strategy is fundamentally different from conventional nonsteroidal contraceptive methods as it represents an innovative bioengineering concept intended to reach the human testing phase (i.e., IND milestone) much faster and at a lower cost than conventional development programs focusing on medicinal chemistry approaches. In this administrative supplement, we will test whether incorporation of drug molecules intended for pharmaco- logical modulation within the vaginal cavity alters the engineering design space and contraceptive efficacy of SMART polymer fibers. In Aim #1, we will delineate electrospinning engineering parameters for non-woven, SMART fiber mats that contain amphiphilic microbicides exhibiting different physiochemical properties. We will test their ability to rapidly reconstitute into an acidic gel phase that exhibits desired mucoadhesive and biore- sponsive properties. In Aim #2, we will assess contraceptive efficacy of microbicide-containing SMART fiber mats in vitro and compare the results to drug-free SMART polymer fibers. Collectively, these results will define the adaptive space for clinical development of SMART polymer fibers to meet women’s preference.