Pharmaceutics

18 pages, 2895 KB

Open AccessArticle

Engineered Polylactic Acid (PLA) Microcapsules for Spatiotemporally Coupled Delivery and Synergistically Enhanced Dual Immunity

by Shaoyu Guan, Yu Zhang, Hongyi Liu, Jialu Li, Lisha Wang, Jing Wang, Hua Yue and Fenghua Xu

Pharmaceutics 2026, 18(4), 456; https://doi.org/10.3390/pharmaceutics18040456 (registering DOI) - 9 Apr 2026

Abstract

Background: With the evolving paradigm of vaccine development, microcapsules have attracted considerable research interest as particulate adjuvants over the past decades. However, the rational engineering design of microcapsule-based composite adjuvant systems to elicit robust immune responses remains a significant challenge. Methods: This study [...] Read more.

Background: With the evolving paradigm of vaccine development, microcapsules have attracted considerable research interest as particulate adjuvants over the past decades. However, the rational engineering design of microcapsule-based composite adjuvant systems to elicit robust immune responses remains a significant challenge. Methods: This study developed polylactic acid (PLA) microcapsules with spatiotemporally coupled delivery and immunopotentiator properties. The resulting formulations were assessed for humoral and cellular immune responses in mice. Results: We prepared uniform-sized microcapsules (MC) and formulated them with monophosphoryl lipid A (MPLA) as a composite component (MPLA@MC), with hydrodynamic diameters of 4.58 μm and 4.12 μm, respectively. Such composite adjuvants, when loaded with ovalbumin (OVA) to form OVA@MC and OVA&MPLA@MC, promoted cellular uptake and activation, exhibiting preferred lysosomal escape advantages. For in vivo experiments, microcapsule-based vaccines elevated serum levels of IgG antibody, and OVA&MPLA@MC induced Th1-biased antibody responses. Specifically, OVA&MPLA@MC also elicited strong cellular immune responses compared to other vaccines, as evidenced by increased secretion of Interferon-γ (IFN-γ) in mouse splenocytes and Granzyme B (Gzmb) in T cells. Mechanistically, muscle tissues at the injection site showed that microcapsule-based vaccines enhanced the recruitment for phagocytosis. Meanwhile, bulk RNA sequencing (RNA-seq) confirmed extensive activation of immune responses and related signaling pathways. Conclusions: This rationally designed composite strategy for spatiotemporally coupled delivery serves as a potent platform for orchestrating synergistic immune responses, opening up new avenues for the development of effective therapeutic and anti-infectious vaccines. Full article

(This article belongs to the Section Drug Delivery and Controlled Release)

► Show Figures

Figure 1

19 pages, 17396 KB

Open AccessReview

Toward a Genomics-Driven Hepatology: Liver Biology, Precision Diagnosis, and the Rise in Genetic Therapies

by Sri Harsha Boppana, Naveena Luke, Sravani Karuchola, Jahnavi Udaikumar and Cyrus David Mintz

Pharmaceutics 2026, 18(4), 455; https://doi.org/10.3390/pharmaceutics18040455 - 8 Apr 2026

Abstract

The liver’s anatomic position and immune specialization make it both a major target and a major filter for systemically delivered therapeutics. Because portal venous inflow exposes the liver early to gut-derived molecules and exogenous compounds, many intravenously administered agents, including gene-based medicines and [...] Read more.

The liver’s anatomic position and immune specialization make it both a major target and a major filter for systemically delivered therapeutics. Because portal venous inflow exposes the liver early to gut-derived molecules and exogenous compounds, many intravenously administered agents, including gene-based medicines and their viral and non-viral delivery systems, preferentially enter and accumulate in hepatic tissue. This review synthesizes how core liver physiology and immunobiology influence the performance, safety, and clinical translation of genomic medicines in hepatology, and outlines near-term practice and research shifts likely to define a genomics-driven future in liver disease care. We review the hepatic microarchitecture relevant to therapeutic trafficking, including sinusoidal transit, the space of Disse, hepatocyte uptake, and hepatobiliary elimination, and highlight the gatekeeping roles of liver sinusoidal endothelial cells and Kupffer cells in clearing particulate material and shaping inflammatory signaling. We then discuss how these same features create both opportunities, such as efficient hepatic targeting, and constraints, including innate immune activation, vector clearance, and variable intrahepatic distribution, for DNA- and RNA-based platforms. Finally, we propose five actionable developments poised to move genomics from a niche tool to a routine component of hepatology practice: earlier genomic testing in unexplained liver disease, multidisciplinary hepatology genome rounds, a centralized liver-specific gene resource, genetics-aware clinical trial design, and expansion of genetic therapies. Integrating liver biology with genomic medicine is essential to improve diagnostic yield, personalize therapy, and accelerate translation of gene-based treatments while mitigating immunologic and delivery-related barriers. Full article

(This article belongs to the Special Issue Advances in Pharmaceutics, Genomics, and Biotechnology for Liver Disease Therapy)

► Show Figures

Graphical abstract

26 pages, 8260 KB

Open AccessArticle

A Nanoliposome Platform Co-Delivery of Hydroxypinacolone Retinoate and Carnosine for Enhanced Epidermal/Dermal Delivery and Multi-Functional Anti-Aging Efficacy

by Siyuan Chen, Lihao Gu, Ruili Zhao, Lihua Zhang, Lina Yao, Jingning Shen, Dan Luo, Xi Wang, Dan Chen, Si Zhao, Hong Zhou and Wei Liu

Pharmaceutics 2026, 18(4), 454; https://doi.org/10.3390/pharmaceutics18040454 - 8 Apr 2026

Abstract

Background: Effective anti-aging requires dual strategies to stimulate regeneration and counteract damage. While the combination of hydroxypinacolone retinoate (HPR) and carnosine (CA) holds great promise, their effectiveness is hampered by instability and poor skin penetration. Methods: To overcome these challenges, this study developed [...] Read more.

Background: Effective anti-aging requires dual strategies to stimulate regeneration and counteract damage. While the combination of hydroxypinacolone retinoate (HPR) and carnosine (CA) holds great promise, their effectiveness is hampered by instability and poor skin penetration. Methods: To overcome these challenges, this study developed HPR and CA co-encapsulated nanoliposomes (HC-NLPs) via high-pressure homogenization as an advanced epidermal/dermal delivery system. Results: HC-NLPs markedly improved skin retention of HPR (58.97%) and CA (111.36%) compared to the free combination (Free-HC). In cellular studies, HC-NLPs displayed excellent biocompatibility and demonstrated a 4.7-fold higher cellular uptake. This led to enhanced proliferative (EdU positive rate increased by 78.32%) and migratory (wound closure improved by 31.5%) capacities. Moreover, HC-NLPs effectively reinforced multiple skin-protective processes associated with aging, including enhanced resistance to oxidative and glycation-induced damage, suppressed inflammatory responses, and strengthened cellular barrier integrity. In 3D skin models, HC-NLPs promoted collagen deposition and improved tissue morphology compared to Free-HC. Their superior in vivo antioxidant and anti-aging effects were further validated in Zebrafish assays. HC-NLPs effectively co-deliver HPR and CA, markedly improving their stability, skin penetration, and cellular internalization. Conclusions: The formulation demonstrates comprehensive pro-regenerative, anti-inflammatory, antioxidative, and anti-glycation effects, representing a promising nano-delivery strategy for advanced anti-aging skincare. Full article

(This article belongs to the Special Issue Advanced Research on Transdermal Drug Delivery)

► Show Figures

Figure 1

22 pages, 6498 KB

Open AccessArticle

Challenges in the Oral Administration of Gastro-Resistant Formulations: The Role of Vehicles and Bottled Waters

by Adrienn Katalin Demeter, Dóra Farkas, Márton Király, Ádám Tibor Barna, Krisztina Ludányi, István Antal and Nikolett Kállai-Szabó

Pharmaceutics 2026, 18(4), 453; https://doi.org/10.3390/pharmaceutics18040453 - 8 Apr 2026

Abstract

Background/Objectives: Gastro-resistant multiparticulate systems are designed to protect drugs in acidic environments and to ensure intestinal release. In practice, the method of administration may need to be modified: pellet-containing capsules opened or tablets halved for patients with swallowing difficulties, yet the type [...] Read more.

Background/Objectives: Gastro-resistant multiparticulate systems are designed to protect drugs in acidic environments and to ensure intestinal release. In practice, the method of administration may need to be modified: pellet-containing capsules opened or tablets halved for patients with swallowing difficulties, yet the type of liquid used for administration is often not specified. This study examined the stability of gastro-resistant coated pellets after exposure to various aqueous media prior to ingestion. Methods: To evaluate administration instructions, 103 Summaries of Product Characteristics of gastro-resistant products were reviewed. Pellets were produced using a bottom-spray fluidized bed process and coated with Eudragit L 30 D-55. Dissolution testing in pH 1.2 medium was performed after pre-soaking the pellets for 5, 15, and 30 min in beverages with various pH and conductivity. Drug release was measured by UV-VIS method, and morphological changes were assessed by image analysis. Marketed gastro-resistant products were also examined visually. Results: SmPC review revealed that the beverage for intake was frequently unspecified. Among the tested beverages differences in pH and conductivity were observed. Alkaline medicinal mineral waters induced increased and time-dependent premature drug release compared to tap and filtered water. Image analysis indicated a reduction in surface area after exposure to alkaline media. Conclusions: Contact with non-specified aqueous media before swallowing may weaken the protective function of gastro-resistant films. More explicit recommendations on suitable administration manipulation and media may improve therapeutic consistency. Full article

(This article belongs to the Special Issue Advances in the Preparation and Technology of Pharmaceutical Solid Dosage Forms)

► Show Figures

Graphical abstract

29 pages, 4375 KB

Open AccessArticle

Application of AI in Tablet Development: An Integrated Machine Learning Framework for Pre-Formulation Property Prediction

by Masugu Hamaguchi, Tomoki Adachi and Noriyoshi Arai

Pharmaceutics 2026, 18(4), 452; https://doi.org/10.3390/pharmaceutics18040452 - 8 Apr 2026

Abstract

Background/Objectives: Tablet development requires simultaneous optimization of multiple quality attributes under limited experimental budgets, yet formulation–property relationships are highly nonlinear in mixture systems. To support pre-formulation decision-making prior to extensive tablet prototyping, this study proposes an AI framework that organizes formulation and process [...] Read more.

Background/Objectives: Tablet development requires simultaneous optimization of multiple quality attributes under limited experimental budgets, yet formulation–property relationships are highly nonlinear in mixture systems. To support pre-formulation decision-making prior to extensive tablet prototyping, this study proposes an AI framework that organizes formulation and process data together with raw-material property records into a reusable database, and enriches conventional composition/process features with physically motivated mixture descriptors derived from raw-material properties and formulation/process settings. Methods: Mixture-level scalar descriptors are constructed by composition-weighted aggregation of material properties, and particle size distribution (PSD) is incorporated via a compact set of summary statistics computed from composition-weighted mixture PSDs. Three feature sets are compared: (i) Materials + Processes (MP), (ii) MP with scalar Descriptors (MPD), and (iii) MPD with PSD summaries (MPDD). Five target properties are modeled: hardness, disintegration time, flow function, cohesion, and thickness. We train and evaluate Random Forest, Extra Trees Regressor, Lasso, Partial Least Squares, Support Vector Regression, and a multi-branch neural network that processes the three feature blocks separately and concatenates them for prediction. For interpolation assessment, repeated Train/Dev/Test splitting (5:3:2) across multiple random seeds is used, and the effect of feature augmentation is quantified by paired RMSE improvements with bootstrap confidence intervals and paired Wilcoxon signed-rank tests. To assess robustness under practical formulation updates, rolling-origin time-series splits are employed and Applicability Domain indicators are computed to characterize out-of-distribution coverage. Results: Across interpolation evaluations, mixture-descriptor augmentation (MPD/MPDD) improves hardness and disintegration time in most settings, whereas gains for flow function are smaller and cohesion/thickness show mixed effects under limited sample sizes. Conclusions: Under extrapolation-oriented evaluation, the descriptors can improve hardness but may degrade disintegration-time prediction under covariate shift, emphasizing the need for careful descriptor selection and dimensionality control when deploying pre-formulation predictors. Full article

(This article belongs to the Special Issue Advancements in Tablet Formulation and Technological Innovations in Pharmaceutical Manufacturing)

► Show Figures

Figure 1

36 pages, 1993 KB

Open AccessReview

Cyclodextrin-Based Strategies for Brain Drug Delivery: Mechanistic Insights into Blood–Brain Barrier Transport and Therapeutic Applications

by Pirscoveanu Denisa Floriana Vasilica, Pluta Ion Dorin, Carmen Vladulescu, Cristina Popescu, Diana-Maria Trasca, Kristina Radivojevic, Renata Maria Varut, Ștefănița Bianca Vintilescu, Mioara Desdemona Stepan and George Alin Stoica

Pharmaceutics 2026, 18(4), 451; https://doi.org/10.3390/pharmaceutics18040451 - 7 Apr 2026

Abstract

Cyclodextrins (CDs) have gained increasing attention as versatile platforms for enhancing drug delivery to the central nervous system, particularly in overcoming the restrictive properties of the blood–brain barrier (BBB). Owing to their unique cyclic oligosaccharide structure, CDs are capable of forming inclusion complexes [...] Read more.

Cyclodextrins (CDs) have gained increasing attention as versatile platforms for enhancing drug delivery to the central nervous system, particularly in overcoming the restrictive properties of the blood–brain barrier (BBB). Owing to their unique cyclic oligosaccharide structure, CDs are capable of forming inclusion complexes with a wide range of therapeutic agents, thereby improving their solubility, stability, and bioavailability. In addition to their role as excipients, growing evidence indicates that CDs can actively modulate biological processes, including membrane fluidity and cholesterol homeostasis, which are critical factors in neurological disorders. This review explores the application of CDs in facilitating drug transport across the BBB through multiple mechanisms, including carrier-mediated transport, receptor-mediated transcytosis, and nanoparticle-based delivery systems. Special emphasis is placed on their use in the treatment of neurodegenerative and neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, Niemann–Pick type C disease, and other central nervous system disorders. In these contexts, CD-based formulations have demonstrated the ability to enhance brain targeting, reduce pathological protein aggregation, and improve therapeutic outcomes in preclinical models. This review uniquely integrates cyclodextrin’s physicochemical properties with specific blood–brain barrier transport mechanisms, proposing a structure–transport–therapy framework that enables a more predictive understanding of brain-targeted drug delivery. Full article

(This article belongs to the Special Issue New Insights into Cyclodextrin-Based Drug Delivery Systems)

► Show Figures

Graphical abstract

32 pages, 711 KB

Open AccessReview

Recent Advances in Particle Design for High-Concentration Protein Suspension Injectables

by Yijing Huang, Chanakya D. Patil, Kinnari Santosh Arte, Jiaying Liu, Haichen Nie, Qi Tony Zhou and Li Lily Qu

Pharmaceutics 2026, 18(4), 450; https://doi.org/10.3390/pharmaceutics18040450 - 7 Apr 2026

Abstract

Subcutaneous administration has become an increasingly important route for delivering protein therapeutics, driven by patient convenience and the growing use of self-administration devices. However, conventional subcutaneous injection systems are typically limited to injection volumes of approximately 1–2 mL, posing significant formulation challenges for [...] Read more.

Subcutaneous administration has become an increasingly important route for delivering protein therapeutics, driven by patient convenience and the growing use of self-administration devices. However, conventional subcutaneous injection systems are typically limited to injection volumes of approximately 1–2 mL, posing significant formulation challenges for protein drugs requiring high therapeutic doses. Monoclonal antibodies (mAbs), for example, often require concentrations exceeding 100 mg/mL to enable subcutaneous delivery, which introduces challenges related to limited solubility, elevated viscosity, and an increased risk of physical and chemical instability. Therefore, high-concentration protein suspensions have emerged as a promising formulation strategy to overcome these limitations and enable subcutaneous administration of high-dose proteins. In such systems, therapeutic protein solid particles are suspended in vehicles in which they are insoluble, giving rise to unique considerations related to particle properties, protein stability, and suspension behaviors such as viscosity, injectability, and sedimentation. Accordingly, multiple particle production approaches have been explored to enable the development of ultra-high-concentration protein suspensions (>200 mg/mL). This review article aims to provide a comprehensive overview of particle formation techniques and the relationships between key particle properties and suspension performance attributes relevant to the development of high-concentration protein suspensions for injectable applications, as well as future directions in this field. Full article

(This article belongs to the Special Issue Recent Advances in Injectable Formulations)

► Show Figures

Graphical abstract

21 pages, 5217 KB

Open AccessArticle

Neurocognitive and Memory-Enhancing Effect of Tanacetum vulgare Essential Oil: Involvement of Hippocampal Neurotrophic Signaling

by Borislava Lechkova, Michaela Shishmanova-Doseva, Niko Benbassat, Pepa Atanassova, Nadya Penkova, Petar Hrischev and Zhivko Peychev

Pharmaceutics 2026, 18(4), 449; https://doi.org/10.3390/pharmaceutics18040449 - 6 Apr 2026

Abstract

Background: Scientific interest has grown in naturally derived compounds capable of supporting or enhancing cognitive performance. Tanacetum vulgare L. is an abundant source of secondary metabolites and has been associated with a broad range of biological activities; however, its potential influence on [...] Read more.

Background: Scientific interest has grown in naturally derived compounds capable of supporting or enhancing cognitive performance. Tanacetum vulgare L. is an abundant source of secondary metabolites and has been associated with a broad range of biological activities; however, its potential influence on cognitive function remains largely unexplored. Methods: The present study explored the effects of T. vulgare essential oil (EO) on cognitive performance, hippocampal brain-derived neurotrophic factor (BDNF) expression, and histomorphological alterations in a rat model. Animals were administered T. vulgare EO at doses of 0.5 and 1.5 mL/kg for 28 days and were subjected to a series of behavioral tests after one week of pretreatment. Results: Both doses of EO facilitated the formation of short- and long-term memory traces in the inhibitory avoidance tasks, with a more pronounced effect observed at the lower dose, whereas improvement in passive learning was evident only at the higher dose. Spatial and recognition memory were enhanced at both doses. EO treatment significantly increased hippocampal BDNF expression without inducing pathological alterations. Conclusions: These findings suggest that T. vulgare EO may improve specific hippocampal-dependent cognitive functions, with upregulation of hippocampal BDNF representing a potential underlying mechanism. Full article

(This article belongs to the Special Issue Pharmaceutical Applications and Therapeutic Mechanisms of Substances from Plant Origin)

► Show Figures

Figure 1

13 pages, 2024 KB

Open AccessSystematic Review

Remimazolam Versus Propofol for General Anesthesia in Older Adults Undergoing Colon Cancer Surgery: A Systematic Review and Meta-Analysis of Comparative Studies

by Khalid I. AlHussaini, Ibrahim Abdullah Abalhassan, Eman Toraih and Abdullah Ibrahim Alhussaini

Pharmaceutics 2026, 18(4), 448; https://doi.org/10.3390/pharmaceutics18040448 - 6 Apr 2026

Abstract

Background: Propofol is widely used for anesthesia in colorectal cancer surgery, but is frequently associated with hypotension and respiratory depression. Remimazolam, a novel ultra-short–acting benzodiazepine, may offer improved hemodynamic stability with similar anesthetic depth and recovery characteristics. However, evidence directly comparing remimazolam and [...] Read more.

Background: Propofol is widely used for anesthesia in colorectal cancer surgery, but is frequently associated with hypotension and respiratory depression. Remimazolam, a novel ultra-short–acting benzodiazepine, may offer improved hemodynamic stability with similar anesthetic depth and recovery characteristics. However, evidence directly comparing remimazolam and propofol in the setting of colon cancer surgery remains limited. Therefore, the aim of this study was to systematically evaluate the efficacy, safety, perioperative hemodynamic stability, and recovery outcomes of remimazolam versus propofol in older adults undergoing colon cancer surgery. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials and comparative cohort studies evaluating remimazolam versus propofol in adult patients undergoing colon or colorectal cancer surgery. PubMed, Scopus, and Web of Science were searched from the start of each database to October 2025. Outcomes included perioperative hemodynamics (MAP and HR), recovery parameters, intraoperative remifentanil consumption, anesthesia duration, and adverse events. Random-effect models were used to calculate pooled mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Results: Six studies involving 542 patients (remimazolam n = 276; propofol n = 266) were included. Remimazolam produced significantly higher perioperative MAP (overall MD = 2.86 mmHg, 95% CI 1.52–4.21; p < 0.0001) and slightly higher HR (MD = 2.30 bpm, 0.08–4.52; p = 0.04). Differences were largest immediately after incision and at the end of surgery. No significant differences were found in PACU stay, overall recovery duration, remifentanil consumption, or anesthesia duration. Postoperative nausea and vomiting were comparable (RR = 0.93; p = 0.86), while respiratory depression was numerically lower with remimazolam (RR = 0.49; p = 0.17). Conclusions: Remimazolam provides anesthetic efficacy comparable to propofol in colon cancer surgery while offering modest, but clinically meaningful improvements in intraoperative hemodynamic stability. Recovery times, opioid requirements, and adverse-event rates were similar between agents. Remimazolam may be particularly advantageous for elderly or hemodynamically vulnerable patients undergoing major colorectal procedures. Larger, high-quality trials are warranted to clarify long-term and oncologic outcomes. Full article

(This article belongs to the Section Clinical Pharmaceutics)

► Show Figures

Figure 1

28 pages, 1279 KB

Open AccessReview

Acute Contractile Effects of Glucagon-like-Peptide-1 Receptor Agonists in the Human Heart

by Joachim Neumann, Uwe Kirchhefer, Britt Hofmann and Ulrich Gergs

Pharmaceutics 2026, 18(4), 447; https://doi.org/10.3390/pharmaceutics18040447 - 6 Apr 2026

Abstract

Glucagon-like-peptide-1 receptor (GLP-1R) agonists are under development as new drugs to treat type 2 diabetes, liver disease, obesity and cardiovascular diseases. Some of these drugs are solely agonists of the GLP-1R. It turned out that their benefit could be improved when they also [...] Read more.

Glucagon-like-peptide-1 receptor (GLP-1R) agonists are under development as new drugs to treat type 2 diabetes, liver disease, obesity and cardiovascular diseases. Some of these drugs are solely agonists of the GLP-1R. It turned out that their benefit could be improved when they also stimulated the glucagon receptor (GCGR) and/or the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR). Stimulation of GLP-1R in cell cultures but also in neonatal atrial and/or ventricular cardiomyocytes and adult atrial cardiomyocytes raised the activity of adenylyl cyclase and thus augmented the 3’,5’cyclic adenosine monophosphate (cAMP) levels. We discuss here the acute contractile effects of such agonists on isolated human atrial and ventricular cardiac preparations from failing and non-failing hearts. We address the receptors involved, GLP-1R expression in various cardiac regions of the human heart, single and multiple receptor agonists and the post-receptor signal transduction system of the GLP-1R in the human heart. Some of the new drugs addressed are still in the early phases of clinical development. We critically discuss the experimental and clinical data available and we also define research needs for experimental and clinical studies. Full article

(This article belongs to the Special Issue GLP-1 Receptor Agonists: Current Understanding and Emerging Therapeutic Horizons)

► Show Figures

Figure 1

37 pages, 2757 KB

Open AccessReview

Antisense Oligonucleotides: Technological Advances, Clinical Progress, and Expanding Therapeutic Frontiers

by Liping Xu, Huaqun Zhang, Bingchen Jiang, Yuanying Jiang and Hui Lu

Pharmaceutics 2026, 18(4), 446; https://doi.org/10.3390/pharmaceutics18040446 - 4 Apr 2026

Abstract

Antisense oligonucleotides (ASOs) are emerging therapeutic agents that modulate gene expression at the RNA level, offering distinct therapeutic advantages over conventional small-molecule drugs and biologics. By directly targeting RNA, ASOs expand the spectrum of druggable targets to include those previously considered “undruggable”, and [...] Read more.

Antisense oligonucleotides (ASOs) are emerging therapeutic agents that modulate gene expression at the RNA level, offering distinct therapeutic advantages over conventional small-molecule drugs and biologics. By directly targeting RNA, ASOs expand the spectrum of druggable targets to include those previously considered “undruggable”, and enable shorter development timelines with improved research and development efficiency. These attributes position ASOs as a highly promising platform for precision and personalized medicine. Recent advances in chemical modification strategies and delivery technologies have markedly accelerated their clinical translation. This review systematically examines the technological evolution of ASO therapeutics, detailing their mechanisms of action, key chemical modification strategies, and advanced delivery systems. It also provides a comprehensive overview of the current global clinical landscape, including approved drugs, discontinued candidates, and ongoing clinical trials. Finally, this review discusses the major challenges facing the field and outlines future directions, with the aim of informing subsequent basic research and clinical development efforts. Full article

(This article belongs to the Section Gene and Cell Therapy)

► Show Figures

Figure 1

18 pages, 2234 KB

Open AccessArticle

Model-Based Design of Sustained-Release Formulations of Anti-TNF-α Monoclonal Antibodies for Intravitreal Administration

by Javier Reig-López, Marina Cuquerella-Gilabert, Javier Zarzoso-Foj, Víctor Mangas-Sanjuán, Virginia Merino and Matilde Merino-Sanjuán

Pharmaceutics 2026, 18(4), 445; https://doi.org/10.3390/pharmaceutics18040445 - 4 Apr 2026

Abstract

Background/Objectives: While intravitreal administration allows for increased ocular exposure to anti-TNF-α monoclonal antibodies, there is still a need for developing delivery systems able to prolong ocular drug exposure and alleviate patient compliance and safety concerns because of repeated injections. Therefore, the objective [...] Read more.

Background/Objectives: While intravitreal administration allows for increased ocular exposure to anti-TNF-α monoclonal antibodies, there is still a need for developing delivery systems able to prolong ocular drug exposure and alleviate patient compliance and safety concerns because of repeated injections. Therefore, the objective of this work was to guide the design of sustained-release formulations of anti-TNF-α monoclonal antibodies for intravitreal administration through a model-based strategy in non-infectious uveitis in the preclinical setting. Methods: Using an in-house-developed anterior uveitis disease model in rats, an intravenous reference dose reducing free TNF-α by 90% at the biophase was established. Intravitreal administrations of sustained-release formulations every 24 weeks were then simulated for adalimumab, golimumab and infliximab to evaluate TNF-α kinetics in the anterior chamber of the eye at different release rates. The selected sustained-release formulation was further evaluated for possible formulation issues causing device emptying before the next administration. Results: Intravitreal administration of sustained-release formulations releasing adalimumab, golimumab or infliximab at 1.802, 0.979 and 1.442 μg/week, respectively, met the predefined criteria of ≥90% reduction in free TNF-α at the biophase. TNF-α levels in aqueous humour were anticipated to be the most sensitive to detect possible formulation issues. Formulation emptying 10, 4 or 8 weeks for adalimumab, golimumab and infliximab, respectively, before next administration triggered TNF-α reaching pathological levels at week 24 post-dose. Conclusions: This work underscores the potential of new approach methodologies in the preclinical drug development of sustained-release formulations for intravitreal administration in ocular inflammatory disorders with less animal testing and without compromising the accuracy of model-informed predictions for human translation. Full article

(This article belongs to the Special Issue Advancing Biologic Drug Development Through Physiologically Based Pharmacokinetic Modelling and Simulations)

► Show Figures

Figure 1

19 pages, 1425 KB

Open AccessArticle

Hot-Melt Pneumatic Extrusion-Based 3D-Printed Bilayer Tablets Enabling Sequential Release of Levocetirizine and Montelukast

by Ga-Ram Kim, Ji-Young Cho, Seung-Wuk Lee and Hyo-Eon Jin

Pharmaceutics 2026, 18(4), 444; https://doi.org/10.3390/pharmaceutics18040444 - 3 Apr 2026

Abstract

Background/Objectives: This study aimed to develop bilayer tablets using hot-melt pneumatic extrusion (HMPE)-based 3D printing for the integrated treatment of allergic rhinitis and asthma. The formulation combined levocetirizine dihydrochloride (immediate release) and montelukast sodium (delayed release) within a single dosage form to [...] Read more.

Background/Objectives: This study aimed to develop bilayer tablets using hot-melt pneumatic extrusion (HMPE)-based 3D printing for the integrated treatment of allergic rhinitis and asthma. The formulation combined levocetirizine dihydrochloride (immediate release) and montelukast sodium (delayed release) within a single dosage form to provide a sequential-release formulation strategy relevant to the intended pharmacological roles of the two drugs. Distinct polymer matrices were selected for each drug layer to ensure mechanical robustness, stability, and appropriate release characteristics. Methods: The printed tablets were systematically characterized by mechanical testing, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and in vitro dissolution. Drug content uniformity was evaluated in accordance with USP <905>. Results: The tablets satisfied USP standards for content uniformity and exhibited sufficient mechanical strength for handling and packaging. DSC and PXRD analyses indicated amorphization of levocetirizine within the polymer matrix, while the amorphous state of the raw montelukast used in this study was retained after printing. In vitro dissolution tests demonstrated immediate release of levocetirizine in acidic medium (pH 1.2) and delayed release of montelukast at intestinal pH (6.8), thereby achieving the intended dual-phase release profile. Conclusions: These findings demonstrate the feasibility of fabricating an HMPE-based 3D-printed bilayer tablet integrating immediate-release levocetirizine and delayed-release montelukast, with reproducible dual-phase release and drug-specific solid-state and performance characteristics within a single oral dosage form. Full article

(This article belongs to the Special Issue Pharmaceutical Solid Dosage Forms: Manufacturing, Design, Development, and Biomedical Applications)

► Show Figures

Graphical abstract

23 pages, 2004 KB

Open AccessArticle

Polymer-Based Microencapsulation of Hedychium coronarium Rhizome Essential Oil for Enhanced Bioactivity Stability and Reduced Irritation

by Pattiya Tammasorn, Wannaree Charoensup, Watchara Kanjanakawinkul, Wei-Chao Lin, Thomas Rades and Wantida Chaiyana

Pharmaceutics 2026, 18(4), 443; https://doi.org/10.3390/pharmaceutics18040443 - 3 Apr 2026

Abstract

Background: Plant-derived essential oils possess valuable bioactivities, but their application is limited by volatility and irritation, which may be addressed through natural polymer encapsulation. This study aimed to investigate the bioactivity of Hedychium coronarium rhizome essential oil and evaluate the effect of [...] Read more.

Background: Plant-derived essential oils possess valuable bioactivities, but their application is limited by volatility and irritation, which may be addressed through natural polymer encapsulation. This study aimed to investigate the bioactivity of Hedychium coronarium rhizome essential oil and evaluate the effect of microencapsulation on its physicochemical characteristics, biological stability, and irritation profile. Methods: Essential oil was extracted from H. coronarium rhizomes by hydrodistillation and chemically characterized. Enzyme inhibitory activities against elastase, hyaluronidase, and tyrosinase were assessed. Microencapsulation was performed using gum Arabic or maltodextrin at 1–5% w/w oil loadings. The resulting powders were evaluated for morphology, entrapment efficiency, hygroscopicity, water activity, biological stability, and irritation potential using the hen’s egg test on the chorioallantoic membrane. Results: The essential oil demonstrated strong enzyme inhibition, particularly against hyaluronidase (IC₅₀ = 0.1 ± 0.0 µg/mL), along with notable elastase and tyrosinase inhibition. Encapsulation significantly reduced irritation scores from 13.3 ± 1.4 for the free oil to 3.6–4.2 for encapsulated systems (p < 0.05). Gum Arabic produced rough, porous particles with lower hygroscopicity, while maltodextrin yielded smoother particles with lower water activity. Both encapsulated powders significantly enhanced biological stability compared with the ethanolic solution. Conclusions: Natural polymer-based microencapsulation effectively reduced the irritation potential and improved the handling properties of H. coronarium essential oil, supporting its potential application in topical bioactive delivery systems. Full article

(This article belongs to the Special Issue Natural Compounds in Drug Delivery Systems)

► Show Figures

Figure 1

12 pages, 2586 KB

Open AccessArticle

Hydrodynamic Delivery of IL-10 Gene for Local Immunomodulation in Human Crohn’s Disease Tissue: A Proof-of-Concept Study

by Luis Sendra, Francisco Giner, Gladys G. Olivera-Pasquini, María José Herrero, Enrique G. Zucchet, Salvador F. Aliño and Matteo Frasson

Pharmaceutics 2026, 18(4), 442; https://doi.org/10.3390/pharmaceutics18040442 - 2 Apr 2026

Abstract

Background/Objectives: Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that is critical for intestinal immune homeostasis. Despite its therapeutic potential, systemic delivery of IL-10 has failed in clinical trials for inflammatory bowel disease (IBD), largely due to its poor localization and short half-life. [...] Read more.

Background/Objectives: Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that is critical for intestinal immune homeostasis. Despite its therapeutic potential, systemic delivery of IL-10 has failed in clinical trials for inflammatory bowel disease (IBD), largely due to its poor localization and short half-life. Methods: We present a proof-of-concept study demonstrating that hydrodynamic delivery of a naked plasmid bearing the human IL-10 gene to ex vivo human colonic segments from Crohn’s disease patients results in localized IL-10 expression and modulation of inflammatory mediators. Results: Compared to venous administration, arterial delivery yielded significantly higher IL-10 mRNA and protein levels, as well as decreased IL-6 and TNF-α expression. Furthermore, nanoparticle tracing confirmed efficient tissue penetration via the arterial route. Conclusions: These findings establish arterial hydrodynamic delivery as a feasible, non-viral strategy for targeted gene therapy in IBD. Full article

(This article belongs to the Section Gene and Cell Therapy)

► Show Figures

Figure 1

38 pages, 8327 KB

Open AccessReview

Functional Peptides: Comparing Synthetic and Sequence-Engineered Antibiofilm Pharmaceutics

by Bilal Aslam, Muhammad Hassan Khalid and Sulaiman F. Aljasir

Pharmaceutics 2026, 18(4), 441; https://doi.org/10.3390/pharmaceutics18040441 - 2 Apr 2026

Abstract

Biofilm formation is a complex phenomenon employed by microbes to counteract antimicrobials. Biofilm-associated infections are a challenging threat to modern medicine. Antimicrobial peptides (AMPs) are recognized as some of the most promising therapeutics to tackle biofilm-producing and multidrug-resistant (MDR) pathogens. However, stability, toxicity, [...] Read more.

Biofilm formation is a complex phenomenon employed by microbes to counteract antimicrobials. Biofilm-associated infections are a challenging threat to modern medicine. Antimicrobial peptides (AMPs) are recognized as some of the most promising therapeutics to tackle biofilm-producing and multidrug-resistant (MDR) pathogens. However, stability, toxicity, and potency are key issues in the case of naturally occurring AMPs. Next-generation antibiofilm tools, such as synthetic or engineered AMPs, have emerged as a potent therapeutic choice. Synthetic peptides offer structural simplicity, versatility for chemical modification, and increased stability, which makes them capable of effectively disrupting both the biofilm matrix and the bacterial membrane. For engineered peptides, rational sequence modification, hybridization, and computational design are used to overcome limitations related to selectivity, biofilm-specific targeting and regulatory pathway modulation. This review provides a critical evaluation of synthetic and engineered AMPs from various perspectives, such as design strategies, antibiofilm action mechanisms, therapeutic performance, and translational potential. This study sheds light on current advances and emerging technologies, including AI-guided peptide optimization and multifunctional peptide platforms, and thereby sets the stage for the rational development of peptide-based therapeutics aimed at overcoming biofilm-mediated antimicrobial resistance (AMR). Full article

(This article belongs to the Special Issue Antimicrobial Peptides as Promising Therapeutic Agents)

► Show Figures

Figure 1

28 pages, 6760 KB

Open AccessArticle

Quality by Design-Based Formulation Development of an Oral Semaglutide Tablet

by Ji-Hyeon Yoon, Do-Hyub Kim and Joo-Eun Kim

Pharmaceutics 2026, 18(4), 440; https://doi.org/10.3390/pharmaceutics18040440 - 1 Apr 2026

Abstract

Background: This study aimed to investigate, from a scientific and formulation perspective, an oral semaglutide tablet incorporating sodium caprate (C10) as an intestinal absorption enhancer and to optimize its formulation performance using a Quality by Design (QbD)-based approach. Semaglutide—a peptide-based therapeutic—provides effective [...] Read more.

Background: This study aimed to investigate, from a scientific and formulation perspective, an oral semaglutide tablet incorporating sodium caprate (C10) as an intestinal absorption enhancer and to optimize its formulation performance using a Quality by Design (QbD)-based approach. Semaglutide—a peptide-based therapeutic—provides effective glycemic control and weight reduction; however, its extremely low oral bioavailability has limited administration to subcutaneous injection. Although various attempts have been made to improve peptide absorption, achieving consistent delivery through oral routes remains a significant challenge due to enzymatic degradation and poor membrane permeability. Methods: To overcome these limitations, an absorption enhancer (sodium caprate) was incorporated to enhance oral absorption, and a Quality by Design (QbD)-based approach was applied to systematically guide formulation development. Following the definition of the Quality Target Product Profile and critical quality attributes, risk assessments (Preliminary Hazard Analysis and Failure Mode and Effects Analysis) were conducted to identify key formulation factors. A design of experiments approach was then employed to determine the optimal tablet composition. Results: Consequently, the resulting formulation met all predefined quality criteria, including hardness, disintegration, friability, and content uniformity. In addition, the in vitro dissolution profile demonstrated a release pattern comparable to that of the reference product, with similarity factor values of 74.4, 74.7, and 71.3 at pH 1.2, 4.0, and 6.8, respectively. Conclusions: These findings indicate that the formulation can achieve consistent and reproducible quality performance as an oral semaglutide dosage form. The QbD-based formulation design strategy presented in this study provides a robust and broadly applicable approach for developing oral delivery systems for peptide drugs, including semaglutide, and ultimately provides useful formulation insight for future peptide-based oral delivery research. Full article

(This article belongs to the Special Issue GLP-1 Receptor Agonists: Current Understanding and Emerging Therapeutic Horizons)

► Show Figures

Figure 1

40 pages, 5512 KB

Open AccessReview

Framework Nucleic Acids as a Nanocontainer for Delivering Heterogeneous Molecular Drugs

by Miao Yang, Xiufan Lou, Jiahong Song, Jia Wang, Hongzhen Peng and Lihua Wang

Pharmaceutics 2026, 18(4), 439; https://doi.org/10.3390/pharmaceutics18040439 - 1 Apr 2026

Abstract

Framework nucleic acids (FNAs) are a class of nucleic acid-based nanostructures characterized by their unique precise structures, excellent biocompatibility and stability, robust loading capacity, and distinctive distribution and metabolic behaviors. They are widely applied in frontier fields such as nanodevices, biosensing, and drug [...] Read more.

Framework nucleic acids (FNAs) are a class of nucleic acid-based nanostructures characterized by their unique precise structures, excellent biocompatibility and stability, robust loading capacity, and distinctive distribution and metabolic behaviors. They are widely applied in frontier fields such as nanodevices, biosensing, and drug delivery. In recent years, research on FNAs has gradually developed from the design and synthesis of nucleic acid nanostructures to practical applications, particularly in providing precise nanocontainers for heterogeneous molecular drugs such as small molecules, peptides, and proteins. Acting as a drug delivery system, FNA nanocontainers could be utilized to address multiple issues inherent in the application of heterogeneous molecular drugs, including hydrophobicity, affinity, and stability. However, they also face challenges such as low drug carrier capacity, potential immunogenicity, and insufficient long-term stability in vivo, necessitating the development of new strategies. This article focuses on composite drugs of small molecules, peptides, and proteins carried by FNAs, elucidates the design principles of FNA carriers, the interaction modes between FNAs and drug molecules, and the physicochemical properties and biological effects/efficacy of FNA–drug complexes, and summarizes the structure–activity relationship patterns. Furthermore, obstacles limiting clinical transformation are proposed to provide beneficial suggestions for the future development of FNA-based drugs. Full article

(This article belongs to the Special Issue Microfluidic Devices for Encapsulating and Delivering Large Biomolecules)

► Show Figures

Figure 1

24 pages, 7143 KB

Open AccessArticle

Spectroscopic Insights into Nanodiamond–Doxorubicin Interactions in Drug Delivery Systems for Potential Cancer Treatment: “What Is Essential Is Invisible to the Eye”

by Danica Jović, Branislav Jović, Ivana Borišev, Višnja Bogdanović and Aleksandar Djordjevic

Pharmaceutics 2026, 18(4), 438; https://doi.org/10.3390/pharmaceutics18040438 - 1 Apr 2026

Abstract

Background/Objectives: Non-covalent nanocarrier-based systems have become a promising platform as they offer a strategy to improve the efficacy-safety profile of doxorubicin (DOX) without altering its chemical structure. Praised for biocompatibility and rich surface chemistry, nanodiamonds (NDs) have launched as nanocarriers of choice [...] Read more.

Background/Objectives: Non-covalent nanocarrier-based systems have become a promising platform as they offer a strategy to improve the efficacy-safety profile of doxorubicin (DOX) without altering its chemical structure. Praised for biocompatibility and rich surface chemistry, nanodiamonds (NDs) have launched as nanocarriers of choice for advanced cancer therapy. By investigating DOX-ND physicochemical interactions, this work advances the structural understanding of a non-covalent potential anticancer system, which has not been quantitatively experimentally explored so far. Methods: To our knowledge, this is among the first studies combining ultraviolet–visible (UV–VIS) spectroscopy with spectral deconvolution to reveal the redistribution of different DOX species in the presence of NDs. Centrifugation-assisted analysis enabled differentiation between hypothetical labile and stable ND/DOX fractions. Adsorption kinetics was studied, and dynamic light scattering (DLS) measured particle size and zeta potential. In vitro screening was performed in non-malignant fibroblasts (MRC-5) and malignant melanoma (HS294T), glioblastoma (U251), and breast cancer (MCF-7) cells to evaluate ND/DOX combinations. Results: Centrifugation analysis revealed heterogeneous ND-DOX binding. Kinetic experiments showed fast multi-stage adsorption kinetics, best described by a bi-exponential decay function and the Weber–Morris model. DLS suggested stable systems with a particle size within 10–80 nm, predominantly around 20 nm, and positive zeta potential. Comparative in vitro screening demonstrated differential cellular responses across cell types, highlighting the relevance of ND/DOX interactions. Conclusions: The findings contribute to elucidating ND-DOX interactions relevant for the design and optimization of drug delivery systems, emphasizing the importance of spectroscopic insights for the design of nanodiamond-based drug delivery systems. Full article

(This article belongs to the Special Issue Carbon-Based Nanomaterials for Pharmaceutical Applications)

► Show Figures

Graphical abstract

Journal Description

Pharmaceutics

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI