Drug delivery systems for female sexual and reproductive health applications

In this work, two localized drug delivery systems for female health applications were developed and characterized, 1) a mucoadhesive biodissolvable thin film for localized and rapid delivery of lidocaine for the treatment of vestibulodynia and, 2) a 3D printed multipurpose intravaginal ring (IVR) for the sustained co-delivery of antiretrovirals and contraceptive drugs. Cellulose-based polymers were formulated using a solvent casting method and characterized for use as biodissolvable, mucoadhesive, flexible films to deliver lidocaine to the vulvar tissue for localized pain relief. Initially, eight film formulations were selected for investigation and underwent a series of in vitro characterization to understand the film properties and drug release kinetics, and two formulations were selected for further optimization. One formulation (5% w/w HEC) was optimized as a rapid drug releasing (100% in <5 min) for use prior to intercourse, and the second film was designed as a longer acting treatment (≥120 min) meant to be worn for extended relief throughout the day. In vivo safety and pharmacokinetics of the two films were assessed in female BALB/c mice, demonstrating the safety and targeted delivery of lidocaine to the tissue in high concentrations. The rapid and extended lidocaine films provide a more patient-friendly alternative for localized pain relief. A first-in-line 3D printed multipurpose prevention technology (MPT) IVR was developed for prevention of HIV, herpes simplex virus type 2 (HSV-2) and unplanned pregnancy. Continuous liquid interface production (CLIP) 3D printing was used to fabricate IVRs with an internal honeycomb geometry using a silicone-based resin (SIL 30, Carbon). These IVRs were engineered with complex internal geometry and underwent a post-fabrication solvent swelling method in acetone to co-formulate dapivirine, pritelivir, and levonorgestrel. The triple drug IVR MPT was optimized for use over 30 days, where each API exhibited a zero-order release profile over 35 days at or above therapeutic levels in vitro. No drug-drug interactions were observed and storage at 4°C provided long-term stability of the triple drug IVR MPT. In vivo testing of the triple-drug IVR MPT in pigtailed macaques demonstrated sustained release for each API over 28 days. CLIP 3D printed IVRs were well tolerated in vivo and no adverse outcomes were observed.Doctor of Philosoph

Cancer risk among users of neuroleptic medication: a population-based cohort study

It has been suggested that neuroleptic medication may decrease cancer risk. We compared cancer risks in a population-based cohort study of 25 264 users (⩾2 prescriptions) of neuroleptic medications in the county of North Jutland, Denmark, during 1989–2002, with that of county residents who did not receive such prescriptions. Statistical analyses were based on age-standardisation and Poisson regression analysis, adjusting for age, calendar period, COPD, liver cirrhosis or alcoholism, use of NSAID, and, for breast cancer, additionally for use of hormone therapy, age at first birth, and number of children. Use of neuroleptic medications was associated with a decreased risk for rectal cancer in both women and men (adjusted IRRs of 0.61 (95% confidence interval, 0.41–0.91) and 0.82 (0.56–1.19), respectively) and for colon cancer in female users (0.78; 0.62–0.98). Some risk reduction was seen for prostate cancer (0.87; 0.69–1.08), but breast cancer risk was close to unity (0.93; 0.74–1.17). Overall, treatment with neuroleptic medications was not related to a reduced risk of cancer, but for cancers of the rectum, colon and prostate there were suggestive decreases in risk