@article{dahl_whitesell_sharma-huynh_maturavongsadit_janusziewicz_fox_loznev_button_schorzman_zamboni_et al._2022, title={A mucoadhesive biodissolvable thin film for localized and rapid delivery of lidocaine for the treatment of vestibulodynia}, volume={612}, ISSN={["1873-3476"]}, DOI={10.1016/j.ijpharm.2021.121288}, abstractNote={Vestibulodynia (VBD), an idiopathic pain disorder characterized by erythema and pain of the vulvar vestibule (the inner aspect of the labia minora and vaginal opening), is the most common cause of sexual pain for women of reproductive age. Women also feel discomfort with contact with clothing and tampon use. As most women with this disorder only have pain with provocation of the tissue, topical anesthetics applied to the vestibule are the current first line treatment for temporary pain relief. Treatment options are limited due to anatomical constraints of the vestibular region, poor drug retention time, imprecise dosing, leakage, and overall product messiness. In this study we report a novel approach to treatment of VBD using thin film designed to fit the vulvar vestibule and deliver lidocaine locally. Two use cases for VBD treatment were identified 1) rapid drug release (<5 min), for use prior to intercourse and 2) long-acting release (≥120 min) for prolonged use and relief throughout the day. Cellulose-based mucoadhesive thin films were fabricated using a solvent casting method. Three polymers including hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), and hydroxypropylmethycellulose (HMPC), were selected owing to their biocompatibility and ideal properties for film casting. Films casted with HEC, HPC, and HPMC exhibited mucoadhesive properties relative to a control, with the highest mucoadhesive force recorded for films casted with HPC. Effect of media volume, pH, presence of mucin and presence of drug on film dissolution rates were investigated. Dissolution rates were independent of media volume, media pH or drug presence, whereas faster dissolution rates were obtained for all films in presence of mucin. In vitro lidocaine release kinetics were influenced by polymer type, percent drug loading and film casting thickness. Lidocaine release was based on a diffusion mechanism rather than through film dissolution and faster release (∼5 min) was observed for HEC films compared HPC films (∼120 min). Higher drug loading and film thickness resulted in slower and more prolonged release kinetics of lidocaine. All films were biocompatible and exhibited good mechanical properties. Two film formulations (9% w/w HPC with 12% w/w LHC, 5% w/w HEC with 6% w/w LHC) were optimized to meet the two use case scenarios for VBD treatment and moved into in vivo testing. In vivo testing demonstrated the safety of the films in BALB/c mice, and the pharmacokinetic analysis demonstrated the delivery of lidocaine primarily to the vaginal tissue. We demonstrate the ability to develop a mucoadhesive, biodissolvable thin film and fine-tune drug release kinetics to optimize local delivery of lidocaine to the vulva.}, journal={INTERNATIONAL JOURNAL OF PHARMACEUTICS}, author={Dahl, Denali K. and Whitesell, Ashlyn N. and Sharma-Huynh, Preetika and Maturavongsadit, Panita and Janusziewicz, Rima and Fox, Ryan J. and Loznev, Henry T. and Button, Brian and Schorzman, Allison N. and Zamboni, William and et al.}, year={2022}, month={Jan} }
 @article{janusziewicz_shrivastava_dahl_young_bis_whitesell_benhabbour_2022, title={Fundamental investigation of sustained and controlled therapeutics release from 3D printed medical devices}, volume={24}, ISSN={["2468-5194"]}, DOI={10.1016/j.mtchem.2022.100978}, abstractNote={Additive manufacturing has long been acclaimed as the tool for next-generation drug delivery device production. An ongoing challenge has remained with the best method of therapeutic incorporation into these devices as the layering mechanisms associated with 3D printing can be harsh and incompatible with most drugs of interest. We propose a method of post-fabrication absorption, or post-loading, of a silicone-based matrix fabricated with digital light synthesis (DLS). The fundamental mechanisms of this process were investigated using a simplified system of blocks with varied diffusion distances. We determined the critical role of specific surface area in the swelling, uptake, and in vitro release of two model drugs, β-estradiol (hydrophobic) and 2-fluoro-2′-deoxyadenosine (hydrophilic), and found sustained drug delivery to be driven by part geometry. The drug loading method was translated to a therapeutically relevant hydrophilic antiretroviral, 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA, Islatravir®), with sustained delivery over 70 days. Finally, we demonstrated the translation of this method into a medical device (intravaginal ring) using β-estradiol as a model drug. The gentle and efficient post-loading process enables the incorporation and sustained delivery of a range of drugs and opens the door for the exploration of long-term delivery of other active pharmaceutical ingredients (APIs).}, journal={MATERIALS TODAY CHEMISTRY}, author={Janusziewicz, R. and Shrivastava, R. and Dahl, D. K. and Young, I. C. and Bis, M. and Whitesell, A. N. and Benhabbour, S. R.}, year={2022}, month={Jun} }
 @article{prasher_shrivastava_dahl_sharma-huynh_maturavongsadit_pridgen_schorzman_zamboni_ban_blikslager_et al._2021, title={Steroid Eluting Esophageal-Targeted Drug Delivery Devices for Treatment of Eosinophilic Esophagitis}, volume={13}, ISSN={["2073-4360"]}, url={https://www.mdpi.com/2073-4360/13/4/557}, DOI={10.3390/polym13040557}, abstractNote={Eosinophilic esophagitis (EoE) is a chronic atopic disease that has become increasingly prevalent over the past 20 years. A first-line pharmacologic option is topical/swallowed corticosteroids, but these are adapted from asthma preparations such as fluticasone from an inhaler and yield suboptimal response rates. There are no FDA-approved medications for the treatment of EoE, and esophageal-specific drug formulations are lacking. We report the development of two novel esophageal-specific drug delivery platforms. The first is a fluticasone-eluting string that could be swallowed similar to the string test “entero-test” and used for overnight treatment, allowing for a rapid release along the entire length of esophagus. In vitro drug release studies showed a target release of 1 mg/day of fluticasone. In vivo pharmacokinetic studies were carried out after deploying the string in a porcine model, and our results showed a high local level of fluticasone in esophageal tissue persisting over 1 and 3 days, and a minimal systemic absorption in plasma. The second device is a fluticasone-eluting 3D printed ring for local and sustained release of fluticasone in the esophagus. We designed and fabricated biocompatible fluticasone-loaded rings using a top-down, Digital Light Processing (DLP) Gizmo 3D printer. We explored various strategies of drug loading into 3D printed rings, involving incorporation of drug during the print process (pre-loading) or after printing (post-loading). In vitro drug release studies of fluticasone-loaded rings (pre and post-loaded) showed that fluticasone elutes at a constant rate over a period of one month. Ex vivo pharmacokinetic studies in the porcine model also showed high tissue levels of fluticasone and both rings and strings were successfully deployed into the porcine esophagus in vivo. Given these preliminary proof-of-concept data, these devices now merit study in animal models of disease and ultimately subsequent translation to testing in humans.}, number={4}, journal={POLYMERS}, author={Prasher, Alka and Shrivastava, Roopali and Dahl, Denali and Sharma-Huynh, Preetika and Maturavongsadit, Panita and Pridgen, Tiffany and Schorzman, Allison and Zamboni, William and Ban, Jisun and Blikslager, Anthony and et al.}, year={2021}, month={Feb} }