@article{king_shrivastava_shah_maturavongsadit_benhabbour_2023, title={Injectable pH and Thermo-Responsive Hydrogel Scaffold with Enhanced Osteogenic Differentiation of Preosteoblasts for Bone Regeneration}, volume={15}, ISSN={["1999-4923"]}, DOI={10.3390/pharmaceutics15092270}, abstractNote={Bone fractures are common in the geriatric population and pose a great economic burden worldwide. While traditional methods for repairing bone defects have primarily been autografts, there are several drawbacks limiting its use. Bone graft substitutes have been used as alternative strategies to improve bone healing. However, there remain several impediments to achieving the desired healing outcomes. Injectable hydrogels have become attractive scaffold materials for bone regeneration, given their high performance in filling irregularly sized bone defects and their ability to encapsulate cells and bioactive molecules and mimic the native ECM of bone. We investigated the use of an injectable chitosan-based hydrogel scaffold to promote the differentiation of preosteoblasts in vitro. The hydrogels were characterized by evaluating cell homogeneity, cell viability, rheological and mechanical properties, and differentiation ability of preosteoblasts in hydrogel scaffolds. Cell-laden hydrogel scaffolds exhibited shear thinning behavior and the ability to maintain shape fidelity after injection. The CNC-CS hydrogels exhibited higher mechanical strength and significantly upregulated the osteogenic activity and differentiation of preosteoblasts, as shown by ALP activity assays and histological analysis of hydrogel scaffolds. These results suggest that this injectable hydrogel is suitable for cell survival, can promote osteogenic differentiation of preosteoblasts, and structurally support new bone growth.}, number={9}, journal={PHARMACEUTICS}, author={King, Jasmine L. and Shrivastava, Roopali and Shah, Pooja D. and Maturavongsadit, Panita and Benhabbour, Soumya Rahima}, year={2023}, month={Sep} }
 @article{young_pallerla_cottrell_maturavongsadit_prasher_shrivastava_cruz_montgomery_schauer_sykes_et al._2023, title={Long-acting injectable multipurpose prevention technology for prevention of HIV and unplanned pregnancy}, volume={363}, ISSN={["1873-4995"]}, DOI={10.1016/j.jconrel.2023.10.006}, abstractNote={Only condoms are proven to protect against both HIV and unplanned pregnancy, however, poor user acceptability and lack of partner cooperation impede effectiveness. We developed an injectable ultra-long-acting, biodegradable, and removable in-situ forming implant (ISFI) as multipurpose prevention technology (MPT). MPT ISFIs co-formulated an antiretroviral (dolutegravir (DTG)) or cabotegravir (CAB)), and a hormonal contraceptive (etonogestrel (ENG) or medroxyprogesterone acetate (MPA)). All formulations were well-tolerated in mice with no signs of chronic local or systemic inflammation. Plasma CAB and DTG concentrations were above 4× PA-IC90 for 90 days with zero-order and diffusion-controlled absorption, respectively, and no differences when co-formulated with either hormone. Plasma ENG and MPA concentrations were quantifiable for 90 days. Complete removal of CAB/MPA ISFIs resulted in MPA concentrations falling below the limit of quantification after 24 h post-removal, but incomplete CAB elimination from plasma. Collectively, we demonstrated the ability to co-formulate antiretrovirals with contraceptives in an ISFI that is well-tolerated with sustained plasma concentrations up to 90 days.}, journal={JOURNAL OF CONTROLLED RELEASE}, author={Young, Isabella C. and Pallerla, Aryani and Cottrell, Mackenzie L. and Maturavongsadit, Panita and Prasher, Alka and Shrivastava, Roopali and Cruz, Gabriela De la and Montgomery, Stephanie A. and Schauer, Amanda and Sykes, Craig and et al.}, year={2023}, month={Nov}, pages={606–620} }
 @misc{howard_benhabbour_2023, title={Non-Hormonal Contraception}, volume={12}, ISSN={["2077-0383"]}, DOI={10.3390/jcm12144791}, abstractNote={While hormonal contraceptives are efficacious and available in several forms for women, perception of safety and concern over side effects are a deterrent for many. Existing non-hormonal contraceptives include permanent sterilization, copper intrauterine devices (IUDs), chemical/physical barriers such as spermicides and condoms, as well as traditional family planning methods including withdrawal and the rhythm method. Individuals who wish to retain their fertility in the future can achieve highest adherence and efficacy with long-acting, reversible contraceptives (LARCs), though there is only one, the copper IUD, that is non-hormonal. As rates of unintended pregnancies remain high with existing contraceptive options, it is becoming increasingly attractive to develop novel pregnancy prevention methods for both women and men. Non-hormonal contraceptives can target a variety of critical reproductive processes discussed here. This review focuses on identified non-hormonal contraceptive targets and subsequent drug candidates in development.}, number={14}, journal={JOURNAL OF CLINICAL MEDICINE}, author={Howard, Sarah Anne and Benhabbour, Soumya Rahima}, year={2023}, month={Jul} }
 @misc{zanganeh_abbasgholinejad_doroudian_esmaelizad_farjadian_benhabbour_2023, title={The Current Landscape of Glioblastoma Biomarkers in Body Fluids}, volume={15}, ISSN={["2072-6694"]}, DOI={10.3390/cancers15153804}, abstractNote={Glioblastoma (GBM) is a highly aggressive and lethal primary brain cancer that necessitates early detection and accurate diagnosis for effective treatment and improved patient outcomes. Traditional diagnostic methods, such as imaging techniques and tissue biopsies, have limitations in providing real-time information and distinguishing treatment-related changes from tumor progression. Liquid biopsies, used to analyze biomarkers in body fluids, offer a non-invasive and dynamic approach to detecting and monitoring GBM. This article provides an overview of GBM biomarkers in body fluids, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), cell-free RNA (cfRNA), microRNA (miRNA), and extracellular vesicles. It explores the clinical utility of these biomarkers for GBM detection, monitoring, and prognosis. Challenges and limitations in implementing liquid biopsy strategies in clinical practice are also discussed. The article highlights the potential of liquid biopsies as valuable tools for personalized GBM management but underscores the need for standardized protocols and further research to optimize their clinical utility.}, number={15}, journal={CANCERS}, author={Zanganeh, Saba and Abbasgholinejad, Elham and Doroudian, Mohammad and Esmaelizad, Nazanin and Farjadian, Fatemeh and Benhabbour, Soumya Rahima}, year={2023}, month={Aug} }
 @article{young_massud_cottrell_shrivastava_maturavongsadit_prasher_wong-sam_dinh_edwards_mrotz_et al._2023, title={Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection}, volume={14}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-023-36330-5}, abstractNote={Abstract}, number={1}, journal={NATURE COMMUNICATIONS}, author={Young, Isabella C. and Massud, Ivana and Cottrell, Mackenzie L. and Shrivastava, Roopali and Maturavongsadit, Panita and Prasher, Alka and Wong-Sam, Andres and Dinh, Chuong and Edwards, Tiancheng and Mrotz, Victoria and et al.}, year={2023}, month={Feb} }
 @article{joiner_king_shrivastava_howard_cottrell_kashuba_dayton_benhabbour_2022, title={Effects of Injection Volume and Route of Administration on Dolutegravir In Situ Forming Implant Pharmacokinetics}, volume={14}, ISSN={["1999-4923"]}, DOI={10.3390/pharmaceutics14030615}, abstractNote={Due to the versatility of the in situ forming implant (ISFI) drug delivery system, it is crucial to understand the effects of formulation parameters for clinical translation. We utilized ultrasound imaging and pharmacokinetics (PK) in mice to understand the impact of administration route, injection volume, and drug loading on ISFI formation, degradation, and drug release in mice. Placebo ISFIs injected subcutaneously (SQ) with smaller volumes (40 μL) exhibited complete degradation within 30–45 days, compared to larger volumes (80 μL), which completely degraded within 45–60 days. However, all dolutegravir (DTG)-loaded ISFIs along the range of injection volumes tested (20–80 μL) were present at 90 days post-injection, suggesting that DTG can prolong ISFI degradation. Ultrasound imaging showed that intramuscular (IM) ISFIs flattened rapidly post administration compared to SQ, which coincides with the earlier Tmax for drug-loaded IM ISFIs. All mice exhibited DTG plasma concentrations above four times the protein-adjusted 90% inhibitory concentration (PA-IC90) throughout the entire 90 days of the study. ISFI release kinetics best fit to zero order or diffusion-controlled models. When total administered dose was held constant, there was no statistical difference in drug exposure regardless of the route of administration or number of injections.}, number={3}, journal={PHARMACEUTICS}, author={Joiner, Jordan B. and King, Jasmine L. and Shrivastava, Roopali and Howard, Sarah Anne and Cottrell, Mackenzie L. and Kashuba, Angela D. M. and Dayton, Paul A. and Benhabbour, Soumya Rahima}, year={2022}, month={Mar} }
 @article{maturavongsadit_shrivastava_sykes_cottrell_montgomery_kashuba_benhabbour_2021, title={Biodegradable polymeric solid implants for ultra-long-acting delivery of single or multiple antiretroviral drugs}, volume={605}, ISSN={["1873-3476"]}, DOI={10.1016/j.ijpharm.2021.120844}, abstractNote={Lack of adherence is a key barrier to a successful human immunodeficiency virus (HIV) treatment and prevention. We report on an ultra-long-acting (ULA) biodegradable polymeric solid implant (PSI) that can accommodate one or more antiretrovirals (e.g., dolutegravir (DTG) and rilpivirine (RPV)) at translatable human doses (65% wt.) in a single implant. PSIs are fabricated using a three-step process: (a) phase inversion of a drug/polymer solution to form an initial in-situ forming solid implant, (b) micronization of dried drug-loaded solid implants, and (c) compression of the micronized drug-loaded solid powder to generate the PSI. DTG and RPV can be pre-combined in a single PLGA-based solution to make dual-drug PSI; or formulated individually in PLGA-based solutions to generate separate micronized powders and form a bilayer dual-drug PSI. Results showed that in a single or bilayer dual-drug PSI, DTG and RPV exhibited physicochemical properties similar to their pure drug analogues. PSIs were well tolerated in vivo and effectively delivered drug(s) over 180 days with concentrations above 4× PA-IC90 after a single subcutaneous administration. While biodegradable and do not require removal, these PSIs can safely be removed to terminate the treatment if required. The versatility of this technology makes it attractive as an ULA drug delivery platform for HIV and various therapeutic applications.}, journal={INTERNATIONAL JOURNAL OF PHARMACEUTICS}, author={Maturavongsadit, Panita and Shrivastava, Roopali and Sykes, Craig and Cottrell, Mackenzie L. and Montgomery, Stephanie A. and Kashuba, Angela D. M. and Benhabbour, S. Rahima}, year={2021}, month={Aug} }
 @article{maturavongsadit_narayanan_chansoria_shirwaiker_benhabbour_2021, title={Cell-Laden Nanocellulose/Chitosan-Based Bioinks for 3D Bioprinting and Enhanced Osteogenic Cell Differentiation}, volume={4}, ISSN={["2576-6422"]}, DOI={10.1021/acsabm.0c01108}, abstractNote={3D bioprinting has recently emerged as a very useful tool in tissue engineering and regenerative medicine. However, developing suitable bioinks to fabricate specific tissue constructs remains a challenging task. Herein, we report on a nanocellulose/chitosan-based bioink, which is compatible with a 3D extrusion-based bioprinting technology, to design and engineer constructs for bone tissue engineering and regeneration applications. Bioinks were prepared using thermogelling chitosan, glycerophosphate, hydroxyethyl cellulose, and cellulose nanocrystals (CNCs). Formulations were optimized by varying the concentrations of glycerophosphate (80-300 mM), hydroxyethyl cellulose (0-0.5 mg/mL), and CNCs (0-2% w/v) to promote fast gelation kinetics (<7 s) at 37 °C and retain the shape integrity of constructs post 3D bioprinting. We investigated the effect of CNCs and pre-osteoblast cells (MC3T3-E1) on the rheological properties of bioinks, bioink printability, and mechanical properties of bioprinted scaffolds. We demonstrate that the addition of CNCs and cells (5 million cells/mL) significantly improved the viscosity of bioinks and the mechanical properties of chitosan scaffolds post-fabrication. The bioinks were biocompatible and printable at an optimized range of printing pressures (12-20 kPa) that did not compromise cell viability. The presence of CNCs promoted greater osteogenesis of MC3T3-E1 cells in chitosan scaffolds as shown by the upregulation of alkaline phosphatase activity, higher calcium mineralization, and extracellular matrix formation. The versatility of this CNCs-incorporated chitosan hydrogel makes it attractive as a bioink for 3D bioprinting to engineer scaffolds for bone tissue engineering and other therapeutic applications.}, number={3}, journal={ACS APPLIED BIO MATERIALS}, author={Maturavongsadit, Panita and Narayanan, Lokesh Karthik and Chansoria, Parth and Shirwaiker, Rohan and Benhabbour, S. Rahima}, year={2021}, month={Mar}, pages={2342–2353} }
 @misc{king_benhabbour_2021, title={Glioblastoma Multiforme-A Look at the Past and a Glance at the Future}, volume={13}, ISSN={["1999-4923"]}, DOI={10.3390/pharmaceutics13071053}, abstractNote={Gliomas are the most common type of brain tumor that occur in adults and children. Glioblastoma multiforme (GBM) is the most common, aggressive form of brain cancer in adults and is universally fatal. The current standard-of-care options for GBM include surgical resection, radiotherapy, and concomitant and/or adjuvant chemotherapy. One of the major challenges that impedes success of chemotherapy is the presence of the blood–brain barrier (BBB). Because of the tightly regulated BBB, immune surveillance in the central nervous system (CNS) is poor, contributing to unregulated glioma cell growth. This review gives a comprehensive overview of the latest advances in treatment of GBM with emphasis on the significant advances in immunotherapy and novel therapeutic delivery strategies to enhance treatment for GBM.}, number={7}, journal={PHARMACEUTICS}, author={King, Jasmine L. and Benhabbour, Soumya Rahima}, year={2021}, month={Jul} }
 @misc{young_benhabbour_2021, title={Multipurpose Prevention Technologies: Oral, Parenteral, and Vaginal Dosage Forms for Prevention of HIV/STIs and Unplanned Pregnancy}, volume={13}, ISSN={["2073-4360"]}, DOI={10.3390/polym13152450}, abstractNote={There is a high global prevalence of HIV, sexually transmitted infections (STIs), and unplanned pregnancies. Current preventative daily oral dosing regimens can be ineffective due to low patient adherence. Sustained release delivery systems in conjunction with multipurpose prevention technologies (MPTs) can reduce high rates of HIV/STIs and unplanned pregnancies in an all-in-one efficacious, acceptable, and easily accessible technology to allow for prolonged release of antivirals and contraceptives. The concept and development of MPTs have greatly progressed over the past decade and demonstrate efficacious technologies that are user-accepted with potentially high adherence. This review gives a comprehensive overview of the latest oral, parenteral, and vaginally delivered MPTs in development as well as drug delivery formulations with the potential to advance as an MPT, and implementation studies regarding MPT user acceptability and adherence. Furthermore, there is a focus on MPT intravaginal rings emphasizing injection molding and hot-melt extrusion manufacturing limitations and emerging fabrication advancements. Lastly, formulation development considerations and limitations are discussed, such as nonhormonal contraceptive considerations, challenges with achieving a stable coformulation of multiple drugs, achieving sustained and controlled drug release, limiting drug–drug interactions, and advancing past preclinical development stages. Despite the challenges in the MPT landscape, these technologies demonstrate the potential to bridge gaps in preventative sexual and reproductive health care.}, number={15}, journal={POLYMERS}, author={Young, Isabella C. and Benhabbour, Soumya Rahima}, year={2021}, month={Aug} }
 @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} }
 @article{benhabbour_kovarova_jones_copeland_shrivastava_swanson_sykes_ho_cottrell_sridharan_et al._2019, title={Ultra-long-acting tunable biodegradable and removable controlled release implants for drug delivery}, volume={10}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-019-12141-5}, abstractNote={Abstract}, journal={NATURE COMMUNICATIONS}, author={Benhabbour, S. Rahima and Kovarova, Martina and Jones, Clinton and Copeland, Daijha J. and Shrivastava, Roopali and Swanson, Michael D. and Sykes, Craig and Ho, Phong T. and Cottrell, Mackenzie L. and Sridharan, Anush and et al.}, year={2019}, month={Sep} }