1. “Bile Derivative T3K Ameliorates Colitis by Regulating the Intestinal Microbiota–Bile Acid Axis”
by Yu Zhou, Yixiang Zhang, Ying Li, Yu Chen, Xiaoqian Chi, Zhongyu You, Haijing Zhang, Yong Li and Lianqiu Wu
Pharmaceutics 2026, 18(1), 20; https://doi.org/10.3390/pharmaceutics18010020
Available online: https://www.mdpi.com/1999-4923/18/1/20

Cover Story: This study explores the therapeutic potential of the bile acid derivative T3K in ulcerative colitis (UC). Using DSS-induced colitis mice, pseudo-germ-free models, and fecal microbiota transplantation, the authors demonstrate that T3K alleviates colitis by enhancing intestinal barrier integrity, upregulating Mucin2 and tight junction proteins, and restoring gut microbiota homeostasis. T3K specifically enriches beneficial bacteria such as Akkermansia muciniphila; increases levels of BAs like muricholic acid (MCA), lithocholic acid (LCA), and its derivative isoLCA; improves bile acid metabolism; and repairs damaged intestinal mucosa. Its efficacy depends on gut microbiota, confirming that T3K acts through the microbiota–bile acid axis. These findings highlight T3K as a promising candidate for UC treatment.

2. “Advances in Polymer Micelles for Cancer Therapy: From Conventional to Smart Delivery Systems”
by Rayna Georgieva Bryaskova, Krasimir Georgiev Staykov and Damyan Stoyanov Ganchev
Pharmaceutics 2026, 18(2), 177; https://doi.org/10.3390/pharmaceutics18020177
Available online: https://www.mdpi.com/1999-4923/18/2/177

Cover Story: Cancer is one of the leading causes of illness and death worldwide. Despite significant advances in diagnosis and treatment, conventional chemotherapy continues to play a central role in cancer therapy, although its clinical effectiveness remains limited. Nanotechnology-based drug delivery systems, particularly polymer micelle-based systems, have emerged as a powerful approach to overcome the major limitations of conventional chemotherapy. This review highlights recent progress in the use of polymeric micelles for cancer therapy, focusing on the transition from conventional to smart micelles that respond selectively to specific stimuli and summarizes preclinical and clinical studies in this area.

3. “Microbiome-Responsive Hydrogels: From Biological Cues to Smart Biomaterials”
by Rajesh Vadlapatla, Amir Nasrolahi Shirazi, Ajoy Koomer, Judy Weng, Matthew Ernest Ghilarducci, Alai Qudus and Keykavous Parang
Pharmaceutics 2026, 18(3), 284; https://doi.org/10.3390/pharmaceutics18030284
Available online: https://www.mdpi.com/1999-4923/18/3/284

Cover Story: Microbiome-responsive hydrogels (MRHs) represent a new frontier in smart biomaterials, shifting away from conventional physicochemical triggers to biologically meaningful, microbe-derived cues. By harnessing microbial enzymes, metabolites, and quorum-sensing signals, these systems enable a localized, disease-relevant activation for controlled drug release, antibacterial action, and tissue modulation. This emerging paradigm integrates materials science with microbiome biology to achieve enhanced physiological specificity and spatiotemporal precision. As MRHs continue to evolve, they offer a transformative platform for next-generation therapies that dynamically respond to the host–microbe microenvironment, advancing precision medicine and targeted interventions.

4. “Surface-Modified Polymeric Nanoparticles for Glioblastoma Therapy: A Review on Targeting Strategies and Delivery of Repurposed Drugs and Off-Label Non-Alkylating Agents”
by Daniela Maria Sousa, Joana Angélica Loureiro, Maria Carmo Pereira and Maria João Ramalho
Pharmaceutics 2026, 18(4), 435; https://doi.org/10.3390/pharmaceutics18040435
Available online: https://www.mdpi.com/1999-4923/18/4/435

Cover Story: Glioblastoma (GBM) remains one of the most aggressive brain tumors, with limited therapeutic success due to drug resistance and restricted delivery across the blood–brain barrier. In this context, drug repurposing and off-label non-alkylating agents have emerged as promising alternatives to overcome MGMT-mediated resistance. However, their clinical potential is often hindered by poor bioavailability and brain penetration. Surface-modified polymeric nanoparticles offer a versatile strategy to enhance targeted delivery, improving drug accumulation and therapeutic efficacy. This review explores recent advances in ligand-functionalized polymeric nanosystems for the delivery of off-label and repurposed drugs in GBM therapy.

5. “Astaxanthin Delivery Across Administration Routes: Recent Advances to Improve Stability and Bioavailability”
by Laetitia Novelli, Marco Cespi, Diego Romano Perinelli and Giulia Bonacucina
Pharmaceutics 2026, 18(5), 523; https://doi.org/10.3390/pharmaceutics18050523
Available online: https://www.mdpi.com/1999-4923/18/5/523

Cover Story: Astaxanthin (ASX) is a xanthophyll carotenoid widely studied for its antioxidant, cytoprotective, and immunomodulatory effects in humans. ASX neutralizes reactive oxygen species, thereby reducing oxidative stress involved in the onset of several chronic and degenerative diseases. Thanks to these properties, ASX has attracted considerable interest in the pharmaceutical, nutraceutical, and cosmetic sectors. However, ASX application is limited by poor physicochemical stability: it is highly lipophilic; sensitive to light, heat, and oxygen; and shows low bioavailability. To overcome these limitations, various formulation strategies through different administration routes have been developed, particularly encapsulation-based approaches aimed at improving stability, solubility, and therapeutic applications.

6. “Polymeric Nano Drug Delivery Systems for Overcoming Tumor Microenvironment-Mediated Drug Resistance”
by Yonggyu Kang, Jeongeun Kim, Jisu Park, Subin Lee, Youngjin An, Kwang Suk Lim and Hyun-Ouk Kim
Pharmaceutics 2026, 18(6), 674; https://doi.org/10.3390/pharmaceutics18060674
Available online: https://www.mdpi.com/1999-4923/18/6/674

Cover Story: Drug resistance induced by the tumor microenvironment (TME) is a major factor that makes effective cancer treatment difficult. Hypoxia, acidic environment, high interstitial pressure, and abnormal extracellular matrix interactions limit tumor penetration of drugs, and drug efflux and metabolic reprogramming further reduce the therapeutic effect. This study addresses the possibility that polymer-based nanomedicine can overcome these limitations by improving intra-tumor drug delivery, reducing drug loss, and increasing intracellular drug retention. In addition, it also suggests that TME-mediated drug resistance can be overcome and extended to precision cancer treatment through stimulation-responsive release, active targeting, and size-optimized nanoparticle strategies.