Pharmaceutics

23 pages, 3734 KB

Open AccessArticle

Evaluation of the Functional Suitability of Carboxylate Chlorin e₆ Derivatives for Use in Radionuclide Diagnostics

by Mariia Larkina, Anastasia Demina, Nikita Suvorov, Petr Ostroverkhov, Evgenii Plotnikov, Ruslan Varvashenya, Vitalina Bodenko, Gleb Yanovich, Anastasia Prach, Viktor Pogorilyy, Sergey Tikhonov, Alexander Popov, Maxim Usachev, Beatrice Volel, Yuriy Vasil’ev, Mikhail Belousov and Mikhail Grin

Pharmaceutics 2026, 18(1), 23; https://doi.org/10.3390/pharmaceutics18010023 - 23 Dec 2025

Abstract

Radionuclide-based molecular imaging modalities are active and developing areas of functional and molecular diagnosis. Among the radionuclides used for SPECT imaging in oncology, ^99mTc is a leading candidate for radiolabeling. At present, a sufficient number of complexons for ^99mTc have been [...] Read more.

Radionuclide-based molecular imaging modalities are active and developing areas of functional and molecular diagnosis. Among the radionuclides used for SPECT imaging in oncology, ^99mTc is a leading candidate for radiolabeling. At present, a sufficient number of complexons for ^99mTc have been described; however, the development of effective delivery systems for this isotope to the area of interest is a complex research task. The use of tumor-targeting molecules as carriers for radioactive tracers is an effective strategy that has enabled the development of many novel radiopharmaceuticals for cancer imaging. Background: To date, a number of studies have shown tumorotropicity of tetrapyrrole compounds to tumor tissues, in particular derivatives of natural chlorophyll A. Methods: Purification was performed using solid-phase extraction. Assessment of radiochemical yield and purity was performed via radio-ITLC. The in vitro tumor cell accumulation was assessed using SKOV-3 and A-431 cell lines. Dose-dependent biodistribution was evaluated in Nu/J mice bearing epidermoid carcinoma (A-431) xenografts. Results: In this work, we obtained complexes with ^99mTc based on water-soluble carboxylate chlorin e₆ derivatives in order to evaluate their potential for use as SPECT radiopharmaceuticals. We performed radiolabelling optimization of a series of the novel chlorins and primary preclinical studies, including an assessment of the effect of their lipophilicity and charge on tumor uptake. Conclusions: Modification of the periphery of the chlorin macrocycle with chelating groups allows for complexing a wide range of metals, including ^99mTc, which can be used for targeted delivery of the radionuclide to the area of interest. Full article

(This article belongs to the Special Issue Applications of Stable Nuclide and Radionuclides in the Area of Pharmacokinetic Process Control and Targeted Drug Therapy)

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7 pages, 658 KB

Open AccessArticle

Oral Bioavailability of Monoclonal Antibody

by Ashwni Verma, Shengjia Wu and Dhaval K. Shah

Pharmaceutics 2026, 18(1), 22; https://doi.org/10.3390/pharmaceutics18010022 - 23 Dec 2025

Abstract

Background/Objectives: Despite significant interest in the oral delivery of antibodies, the oral bioavailability of monoclonal antibodies (mAbs) is not known to date. To find out an answer to this question, we have performed a preclinical investigation in mice and rats, using a non-binding [...] Read more.

Background/Objectives: Despite significant interest in the oral delivery of antibodies, the oral bioavailability of monoclonal antibodies (mAbs) is not known to date. To find out an answer to this question, we have performed a preclinical investigation in mice and rats, using a non-binding humanized mAb trastuzumab as the prototype molecule. Methods: The antibody was administered at the dose of 100 mg/kg in mice and rats, and plasma pharmacokinetics (PK) was measured for 14 days. Published plasma PK of trastuzumab in mice and rats obtained after intravenous administration was also used for the analysis. Non-compartmental analysis (NCA), as well as compartmental modeling of PK data, was performed to estimate the oral bioavailability of the antibody in mice and rats. Results: It was found that the oral bioavailability of mAb in rats and mice determined using NCA was 0.027% and 0.014%, respectively. The model-estimated oral bioavailability of the mAb in rats and mice was 0.025% and 0.013%, respectively. The rate of absorption of the mAb from the gastrointestinal tract was found to be the same between rats and mice, as 0.78 h-1. Conclusions: Overall, the oral bioavailability of the humanized mAb in rodents was found to be around 0.02%, suggesting only 1 out of 5000 mAb molecules administered orally makes it to the systemic circulation. To the best of our knowledge, this is the first study to report an absolute oral bioavailability value for a mAb. It remains to be seen if the observed value of 0.02% is generalizable across mAb molecules and other animal species, including humans. Full article

(This article belongs to the Special Issue Drug Product Performance: Bioavailability, Relative Bioavailability and Bioequivalence, 2nd Edition)

19 pages, 4111 KB

Open AccessArticle

Non-Crosslinked Hyaluronic Acid Redensity 1^® Supports Cell Viability, Proliferation, and Collagen Deposition in Early Burn Management

by Zhifeng Liao, Xi Chen, Romain Brusini, Jimmy Faivre, Lee Ann Applegate, Killian Flegeau and Nathalie Hirt-Burri

Pharmaceutics 2026, 18(1), 21; https://doi.org/10.3390/pharmaceutics18010021 - 23 Dec 2025

Abstract

Background/Objectives: Burn injuries pose a significant challenge due to tissue damage and impaired healing. Cell-based therapies offer promise by delivering therapeutic cells to the wound site. However, effective cell delivery remains a critical hurdle. This study investigates the potential of non-crosslinked hyaluronic acid [...] Read more.

Background/Objectives: Burn injuries pose a significant challenge due to tissue damage and impaired healing. Cell-based therapies offer promise by delivering therapeutic cells to the wound site. However, effective cell delivery remains a critical hurdle. This study investigates the potential of non-crosslinked hyaluronic acid (HA) as a simple, versatile carrier for delivering autologous keratinocytes and fibroblasts to treat early burn wounds. Methods: Primary keratinocytes and fibroblasts were isolated from uninjured adult skin. In addition, fibroblasts and adipose stem cells (ASC) from polydactyly and progenitor fibroblasts were used. Non-cross-linked HA Redensity 1^® (RD1) solutions of varying concentrations were prepared and applied to various in vitro models. Cell viability, proliferation, migration, and collagen stimulation were assessed using standard assays. Additionally, cells were suspended in Redensity 1 and applied to an in vitro de-epidemalized dermis (DED) wound model to examine cell delivery and tissue reformation. Results: Preliminary data demonstrated the feasibility of using non-cross-linked HA RD1 gel as a cell carrier. RD1 gel enhanced cell viability, retention, migration, and collagen deposition. Histological analysis revealed improved cell adhesion and migration. Conclusions: This study provides valuable insight into the potential of non-cross-linked HA RD1 as a simple and effective delivery vehicle for cell therapies in early burn care. Successful translation of this approach could significantly improve clinical outcomes for burn patients. Full article

(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)

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23 pages, 89938 KB

Open AccessArticle

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 - 23 Dec 2025

Abstract

Background/Objectives: The pathogenesis of ulcerative colitis (UC) is complex, and there is an urgent need for effective therapeutic agents with low side effects. Recent studies highlight the critical roles of abnormal bile acid (BA) metabolism and gut microbiota dysbiosis in UC progression. [...] Read more.

Background/Objectives: The pathogenesis of ulcerative colitis (UC) is complex, and there is an urgent need for effective therapeutic agents with low side effects. Recent studies highlight the critical roles of abnormal bile acid (BA) metabolism and gut microbiota dysbiosis in UC progression. However, there is a significant knowledge gap about the relation between BA and gut microbiota. The BA derivative T3K exerts good anti-UC effect, and its mechanism is still unknown. In this study, we investigate how its anti-UC mechanism is involved in the modulation of the gut microbiota-BA axis and BA metabolism. Methods: Gene expression microarray GSE92415 of UC from the Gene Expression Omnibus was used to analyze BA metabolism. DSS-induced colitis mouse model, Caco-2 and IEC6 cells were used to confirm the anti-UC of T3K using intestinal permeability assay with FITC, Western-blot, immunohistochemical staining, immunofluorescenc and so on in vitro and in vivo. The changes in bile acid and microbiota were measured by 16S rRNA sequencing and bile acid analysis combined with pseudo-germ-free (PGF) models and fecal microbiota transplantation (FMT). Results: T3K demonstrated strong therapeutic effects, including reduced weight loss, lower disease activity index (DAI), and increased colon length. T3K also enhanced the expression of Occludin and Mucin2, and restored gut barrier integrity. Furthermore, T3K improved intestinal dysbiosis and abnormal BA metabolism in colitis mice. Through PGF models and FMT, we confirmed that T3K modulates BA metabolism via the gut microbiota. T3K specifically promotes the growth of beneficial bacteria, such as Akkermansia muciniphila, increases levels of hydrophilic BAs like muricholic acid (MCA), lithocholic acid (LCA) and its derivatives isoLCA and then repairs damaged intestinal mucosa. Conclusions: Bile acid derivative T3K, as a potential anti-UC candidate, effectively restores gut barrier integrity and then ameliorates colitis by improving gut microbiota composition and regulating BA metabolism, including increasing hydrophilic BAs. Full article

(This article belongs to the Special Issue Natural Pharmaceuticals Focused on Anti-inflammatory Activities)

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44 pages, 3873 KB

Open AccessReview

Experimental and Modeling-Based Approaches for Mechanistic Understanding of Pan Coating Process—A Detailed Review

by Behrad Aminahmadi, Elise Vaes, Filip Willemse, Domenica Braile, Luz Naranjo Gomez, Sune Klint Andersen, Thomas De Beer and Ashish Kumar

Pharmaceutics 2026, 18(1), 19; https://doi.org/10.3390/pharmaceutics18010019 - 23 Dec 2025

Abstract

Tablet film coating is governed by three interrelated phenomena, namely, tablet mixing, coating-liquid spraying, and liquid evaporation, which dominate the critical quality attributes (

C Q A s

) of the final product. This review examines how differences in coater design, key process [...] Read more.

Tablet film coating is governed by three interrelated phenomena, namely, tablet mixing, coating-liquid spraying, and liquid evaporation, which dominate the critical quality attributes (

C Q A s

) of the final product. This review examines how differences in coater design, key process parameters, and quality control strategies impact these phenomena and ultimately affect inter-tablet and intra-tablet coating variability. Two complementary approaches for understanding and optimizing the process are evaluated. The experimental approach, involving Design of Experiments (DoE), retrospective data analysis, and advanced Process Analytical Technology (

P A T

), provides empirical insight into factor–response relationships and enables real-time quality assurance. Simultaneously, model-based approaches, including thermodynamic, spray-dynamics, and particle-dynamics modelling, offer mechanistic understanding of heat and mass transfer, droplet deposition patterns, and tablet motion. Although these sub-models have advanced considerably over the years, a predictive model that treats the coating process in its entirety is still missing. Overall, this review underscores that future advancements will require integrating experimental and model-based methodologies to achieve robust, quality-driven, and predictive control of tablet film coating processes. Full article

(This article belongs to the Section Pharmaceutical Technology, Manufacturing and Devices)

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19 pages, 3233 KB

Open AccessArticle

Engineering Human 3D Cardiac Tissues for Predictive Functional Drug Screening

by Ester Sapir Baruch, Daniel Rosner, Elisabeth Riska, Moran Yadid, Assaf Shapira and Tal Dvir

Pharmaceutics 2026, 18(1), 18; https://doi.org/10.3390/pharmaceutics18010018 - 22 Dec 2025

Abstract

Background/Objectives: Cardiotoxicity remains a leading cause of drug withdrawal. Conventional preclinical models, such as two-dimensional (2D) cell cultures and animal studies, often fail to accurately predict human cardiac responses. While 2D cultures lack the complex architecture and dynamic functionality of native myocardium, [...] Read more.

Background/Objectives: Cardiotoxicity remains a leading cause of drug withdrawal. Conventional preclinical models, such as two-dimensional (2D) cell cultures and animal studies, often fail to accurately predict human cardiac responses. While 2D cultures lack the complex architecture and dynamic functionality of native myocardium, interspecies differences limit the translational relevance of animal models. The objective of this study was to develop a human-relevant, in vitro platform that enables predictive and functional assessment of drug-induced cardiotoxicity. Methods: Here, we present a high-throughput in vitro platform for cardiotoxicity screening using three-dimensional (3D) cardiac tissues derived from human induced pluripotent stem cells (hiPSCs) within a thermoresponsive extracellular matrix-derived hydrogel. The hydrogel enables homogeneous encapsulation, differentiation in 3D, and long-term assembly into a functional cardiac tissue. Maturation was validated by immunostaining for cardiac-specific markers, and calcium imaging was employed to monitor electrical signal propagation. Contractile performance, defined by beat rate and contraction amplitude, was quantified using video-based motion analysis. The platform was applied to evaluate the dose-dependent effects of various cardioactive compounds, including β-adrenergic agonists ((-) epinephrine and dopamine), a cardiotoxic chemotherapeutic (doxorubicin), a sinus node inhibitor (ivabradine), a calcium channel blocker (verapamil), and a β-adrenergic antagonist (metoprolol). Results: The engineered cardiac tissues exhibited functional maturation and stable contractile behavior. Drug testing demonstrated compound-specific, dose-dependent functional responses. For each compound, the system faithfully reproduced the expected physiological responses. Conclusions: This human-relevant, scalable platform enables sensitive, multiparametric functional assessment of cardiac tissues, offering a cost-effective and predictive tool for preclinical drug safety testing. By bridging the gap between in vitro assays and human physiology, it holds promise to enhance translational accuracy while reducing reliance on animal models. Full article

(This article belongs to the Section Pharmaceutical Technology, Manufacturing and Devices)

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18 pages, 2670 KB

Open AccessArticle

Effects of Polysaccharide Coating on Cell-Surface Association and Endocytic Uptake of PLGA Nanomicelles in MCF-7 Cells

by Abdulkadir Bahadir Alkan, Esma Nur Develi Arslanhan, Fatemeh Bahadori, Muhammed Zahid Kasapoglu, Fahri Akbas, Seda Susgun, Zahra Eskandari and Ebru Toksoy Oner

Pharmaceutics 2026, 18(1), 17; https://doi.org/10.3390/pharmaceutics18010017 - 22 Dec 2025

Abstract

Background: Targeting cancer tumors using PLGA (Poly(D, L-lactide-co-glycolide)) nanoparticles (NPs) requires clathrin-mediated endocytosis (CME) and lysosomal degradation to provide release within cancer cells. However, Caveolae-mediated endocytosis (CavME) provides lysosomal escape, which is favorable in oral applications. Macropinocytosis (MPC) is a non-targeted way of [...] Read more.

Background: Targeting cancer tumors using PLGA (Poly(D, L-lactide-co-glycolide)) nanoparticles (NPs) requires clathrin-mediated endocytosis (CME) and lysosomal degradation to provide release within cancer cells. However, Caveolae-mediated endocytosis (CavME) provides lysosomal escape, which is favorable in oral applications. Macropinocytosis (MPC) is a non-targeted way of endocytosis, used by immune cells. Methods: In this proof-of-concept study, we investigated how polysaccharide surface coatings modulate the endocytic uptake of FITC-labeled PLGA nanomicelles (FPM) in MCF-7 breast cancer cells using spectrophotometry. This research involved the surface modification of FPM using polysaccharides: cellulose (FPCM) as a polyglucan and Halomonas Levan (FPLM) as a polyfructan, to modify the NP and cell-surface association. Results: MPC was found to be the major internalization pathway for the nanomicelles ~200 nm. However, after surface modification, FPCM and FPM remained highly MPC-dependent with additional CavME/CME involvement, whereas FPLM showed relatively reduced MPC dependence and a higher CME contribution. Conclusion: Overall, the results indicate that simple polysaccharide coatings can bias the relative use of MPC, CME, and CavME for PLGA nanomicelles in MCF-7 cells, providing a basis for pathway-oriented nanocarrier design. Validation by flow cytometry, studies in additional breast cancer cell lines, and transporter-level investigations will be needed to generalize and refine these findings. Full article

(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)

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26 pages, 5138 KB

Open AccessArticle

Tailorable Antibacterial Activity and Biofilm Eradication Properties of Biocompatible α-Hydroxy Acid-Based Deep Eutectic Solvents

by Gleb Dubinenko, Elena Senkina, Ksenia Golovina, Alexandra Myshova, Olga Igumnova, Evgenii Plotnikov, Arsalan Badaraev, Sven Rutkowski, Victor Filimonov and Sergei Tverdokhlebov

Pharmaceutics 2026, 18(1), 16; https://doi.org/10.3390/pharmaceutics18010016 - 22 Dec 2025

Abstract

Background/Objectives: Deep eutectic solvents (DESs) have recently gained attention for their antimicrobial properties, particularly because they target both planktonic bacteria and biofilms. Among these, DESs based on α-hydroxy acids (αHAs) are of interest due to their inherent antibacterial properties and favorable biocompatibility. [...] Read more.

Background/Objectives: Deep eutectic solvents (DESs) have recently gained attention for their antimicrobial properties, particularly because they target both planktonic bacteria and biofilms. Among these, DESs based on α-hydroxy acids (αHAs) are of interest due to their inherent antibacterial properties and favorable biocompatibility. However, effects of the αHA molecular structure and hydrogen bonding ability within a DES formulation on biological activity has not yet been thoroughly investigated. Methods: This study systematically investigates DESs formed by combining glycolic acid, lactic acid or tartaric acid with either choline chloride or tetraethylammonium chloride. Results: All DESs demonstrate broad-spectrum antibacterial activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa and effectively inhibit biofilm formation while exhibiting low cytotoxicity toward 3T3-L1 fibroblasts. Conclusions: DES formation enhances antibacterial efficacy while attenuating cytotoxicity compared to the individual components, thereby decoupling bactericidal activity from toxicity. Physicochemical characterization confirms the formation of a eutectic phase and reveals that biological activity is primarily governed by acidity rather than by the specific αHA structure or eutectic strength. These results provide new insights into structure-function relationships in DESs and establish a design strategy for biocompatible, non-cytotoxic antimicrobial agents. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Drug Delivery)

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14 pages, 2096 KB

Open AccessArticle

Retrospective Validation of Clinical Decision Support Tools for Predicting Effectiveness Outcomes in Inflammatory Bowel Disease Patients Treated with Vedolizumab

by Paul A. G. de Klaver, Amber M. H. van Woerkens, Hedwig M. A. D’Agnolo, Marieke J. Pierik and Luc J. J. Derijks

Pharmaceutics 2026, 18(1), 15; https://doi.org/10.3390/pharmaceutics18010015 - 22 Dec 2025

Abstract

Background/Objectives: Two clinical decision support tools (CDSTs) have been developed to predict treatment effectiveness of vedolizumab in Crohn’s disease (CD) and ulcerative colitis (UC). This study aimed to validate the CDSTs with real-world data from a Dutch teaching hospital. Methods: Patients [...] Read more.

Background/Objectives: Two clinical decision support tools (CDSTs) have been developed to predict treatment effectiveness of vedolizumab in Crohn’s disease (CD) and ulcerative colitis (UC). This study aimed to validate the CDSTs with real-world data from a Dutch teaching hospital. Methods: Patients with CD or UC treated with vedolizumab between October 2014 and July 2023 were included. IBD patients treated with ustekinumab were included to study the specificity of the CDSTs. The primary outcomes were rates of clinical remission (CREM), biochemical remission (BioREM), composite (either clinical or biochemical) remission (CompREM) and corticosteroid-free clinical remission (CSF-CREM) at week 14, 30 and 54. Results: 32 CD patients and 41 UC patients treated with vedolizumab were included, as well as 28 CD patients treated with ustekinumab and 41 UC patients treated with vedolizumab. Among UC patients treated with vedolizumab, rates of CREM, CompREM and CSF-CREM at week 54 were statistically significantly higher in the group with high probability of response compared to the group with low + intermediate probability of response (CREM 33.3% vs. 81.8% p = 0.003; CompREM 33.3% vs. 86.4% p < 0.001; CSF-CREM 22.2% vs. 77.3% p = 0.001). For both CD patients treated with vedolizumab and CD patients treated with ustekinumab, no statistically significant differences were found between low + intermediate and high probability groups for all outcomes. Conclusions: The CDST for UC is able to predict various effectiveness outcomes for treatment with vedolizumab and can therefore help in the selection of optimal treatment for patients with UC. For CD patients treated with vedolizumab, the CDST could not predict effectiveness outcomes. Full article

(This article belongs to the Section Biologics and Biosimilars)

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27 pages, 4082 KB

Open AccessArticle

Biogenic Selenium Nanoparticles from Lactiplantibacillus plantarum as a Potent Antimicrobial Agent Against Methicillin-Resistant Staphylococcus aureus

by Gyeong-min Kim, SeCheol Oh and Kwang-sun Kim

Pharmaceutics 2026, 18(1), 14; https://doi.org/10.3390/pharmaceutics18010014 - 22 Dec 2025

Abstract

Background: Methicillin-resistant Staphylococcus aureus (MRSA) remains a major global health concern owing to its multidrug resistance and persistence despite continued antibiotic development. Eco-friendly nanomaterials such as selenium nanoparticles (SeNPs) have emerged as promising antimicrobial alternatives because of their high biocompatibility and lower toxicity [...] Read more.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) remains a major global health concern owing to its multidrug resistance and persistence despite continued antibiotic development. Eco-friendly nanomaterials such as selenium nanoparticles (SeNPs) have emerged as promising antimicrobial alternatives because of their high biocompatibility and lower toxicity compared to conventional metallic nanoparticles. In this study, we investigated the inhibitory effects and underlying mechanisms of Lactiplantibacillus plantarum (LP)–derived SeNPs (LP-SeNPs) on MRSA. Methods: SeNPs were biosynthesized using the antibacterial cell-free supernatant (CFS) of LP, which provides naturally reducing and stabilizing biomolecules. The resulting LP-SeNPs were characterized by physicochemical and structural analyses and compared to chemically synthesized SeNPs (Chem-SeNPs). Antibacterial activity was assessed through minimum inhibitory concentration (MIC) testing, time-kill kinetics, and cell viability assays. Results: LP-SeNPs, which were spherical with an average diameter of 107 nm, exhibited selective antibacterial activity against Gram-positive bacteria and showed no effect on Gram-negative strains. Notably, all six MRSA isolates demonstrated high susceptibility, with MIC values approximately 100-fold lower than that of S. aureus ATCC 25923, a non-MRSA reference strain. LP-SeNPs were also non-cytotoxic up to 20-fold the MIC (IC₅₀ > 10 µg/mL). Mechanistic analyses indicated that disruption of the bacterial cell membrane was the primary antibacterial mechanism, supported by additional contributions from reactive oxygen species generation and protein synthesis inhibition. Conclusions: LP-SeNPs represent a sustainable, biocompatible, and potent antibacterial nanoplatform with strong selectivity for Gram-positive pathogens, particularly MRSA. These findings highlight their potential as eco-friendly and targeted therapeutic strategies for combating MRSA infections. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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19 pages, 1594 KB

Open AccessArticle

Dual Core-Shell Loaded Lipid-Polymer Hybrid Nanoparticles as Combination Anti-Infective Delivery Platforms

by Valeria Carini, Giulia Scagnetti, Joanne Foulkes, Katie Evans, Imran Saleem and Sarah Gordon

Pharmaceutics 2026, 18(1), 13; https://doi.org/10.3390/pharmaceutics18010013 - 22 Dec 2025

Abstract

Background/Objectives: The growing threat posed by antimicrobial resistance to worldwide public health highlights the urgent need not only for new anti-infective candidates, but also for innovative formulation strategies capable of mediating effective delivery of anti-infective compounds. The current study, therefore, aimed to demonstrate [...] Read more.

Background/Objectives: The growing threat posed by antimicrobial resistance to worldwide public health highlights the urgent need not only for new anti-infective candidates, but also for innovative formulation strategies capable of mediating effective delivery of anti-infective compounds. The current study, therefore, aimed to demonstrate the feasibility of formulating lipid-polymer hybrid nanoparticles (LPHNPs) with dual loading of both core and shell compartments for combination anti-infective delivery. Methods: LPHNPs containing the antibiotic cefotaxime within a chitosan polymer core and the novel antimicrobial peptide RN7IN6 within a bacteria-mimicking lipid shell were produced by microfluidic mixing, and optimized with respect to parameters including total flow rate, flow rate ratio, and lipid concentration. Minimum inhibitory concentrations of cefotaxime and RN7IN6 co-incorporated in LPHNPs were assessed as a preliminary indicator of antibacterial efficacy. Results: Uniformly nanosized LPHNPs were produced, with maximized loading of cefotaxime and RN7IN6 within particle cores and shells, respectively. Empty LPHNPs showed an appreciable antibacterial activity, particularly against the Gram-negative bacterium Escherichia coli, while RN7IN6 was indicated to enhance cefotaxime activity against E. coli when both actives were incorporated in LPHNPs. Conclusions: The current findings clearly demonstrate the feasibility of formulating LPHNPs for core-shell co-encapsulation and delivery of anti-infectives. The promising antibacterial efficacy of co-loaded LPHNPs warrants further in-depth investigation to determine the extent of co-loaded LPHNP applications as combination anti-infective delivery platforms. Full article

(This article belongs to the Special Issue Novel Therapeutic Agents and Innovative Delivery Systems Against Infectious Diseases)

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2 pages, 482 KB

Open AccessCorrection

Correction: Susilo et al. Whole-Body Physiologically Based Pharmacokinetic Modeling Framework for Tissue Target Engagement of CD3 Bispecific Antibodies. Pharmaceutics 2025, 17, 500

by Monica E. Susilo, Stephan Schaller, Luis David Jiménez-Franco, Alexander Kulesza, Wilhelmus E. A. de Witte, Shang-Chiung Chen, C. Andrew Boswell, Danielle Mandikian and Chi-Chung Li

Pharmaceutics 2026, 18(1), 12; https://doi.org/10.3390/pharmaceutics18010012 - 22 Dec 2025

Abstract

Error in Figure [...] Full article

(This article belongs to the Special Issue Development of Physiologically Based Pharmacokinetic (PBPK) Modeling)

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29 pages, 972 KB

Open AccessSystematic Review

A Systematic Review of Advanced Drug Delivery Systems: Engineering Strategies, Barrier Penetration, and Clinical Progress (2016–April 2025)

by Assem B. Uzakova, Elmira M. Yergaliyeva, Azamat Yerlanuly and Zhazira S. Mukatayeva

Pharmaceutics 2026, 18(1), 11; https://doi.org/10.3390/pharmaceutics18010011 - 22 Dec 2025

Abstract

Background/Objectives: Advanced drug delivery systems (DDSs) are essential for targeted delivery, controlled release, and reduced systemic toxicity, but their clinical adoption is limited by biological barriers, manufacturing complexities, and cost. The aim of this systematic review is to critically evaluate the quantitative relationships [...] Read more.

Background/Objectives: Advanced drug delivery systems (DDSs) are essential for targeted delivery, controlled release, and reduced systemic toxicity, but their clinical adoption is limited by biological barriers, manufacturing complexities, and cost. The aim of this systematic review is to critically evaluate the quantitative relationships between platform design, overcoming biological barriers, and clinical translation outcomes for DDS developed between 2016 and 2025. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science (January 2016–April 2025) in accordance with the PRISMA 2020 guidelines. Included studies focused on experimental or clinical data for nanocarrier platforms (liposomes, lipid nanoparticles, polymer systems, biomimetic carriers, extracellular vesicles). Data on platform characteristics, interactions with barriers, pharmacokinetics, manufacturing, and clinical outcomes were extracted and synthesized in narrative form due to the significant methodological heterogeneity. Results: An analysis of 77 included studies confirms that successful clinical translation depends on matching the physicochemical properties of the carrier (size, surface chemistry, material) to specific biological barriers. Liposomes and lipid nanoparticles (LNPs) remain the most clinically validated platforms, exploiting the EPR effect and liver tropism, respectively. Key engineering solutions include stealth coatings, ligand-mediated targeting, and stimulus-responsive materials to overcome barriers such as mononuclear phagocyte system clearance, the blood–brain barrier, and mucosal barriers. Microfluidic and continuous manufacturing processes enable reproducibility, but scalability, cost, and immunogenicity (e.g., anti-PEG responses) remain key translational challenges. Engineered extracellular vesicles, biomimetic carriers, and 3D/4D-printed systems combined with AI-driven design demonstrate the potential for personalized, adaptive delivery. Conclusions: Cutting-edge DDSs have validated their clinical value, but realizing their full potential requires a holistic, patient-centered design approach integrating barrier-specific engineering, scalable manufacturing, and rigorous safety assessment from the earliest stages of development. Further progress will depend on standardizing methods for new platforms (e.g., extracellular vesicles), implementing digital and AI tools, and ensuring translational feasibility as a fundamental principle. Full article

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

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22 pages, 6141 KB

Open AccessArticle

Construction and Characterization of PDA@MnO₂-Cored Multifunctional Targeting Nanoparticles Loaded with Survivin siRNA for Breast Tumor Therapy

by Jing Zhang, Wenhao Jiang, Lei Hu, Qing Du, Nina Filipczak, Satya Siva Kishan Yalamarty and Xiang Li

Pharmaceutics 2026, 18(1), 10; https://doi.org/10.3390/pharmaceutics18010010 - 21 Dec 2025

Abstract

Objective: This study aims to engineer a novel nanoparticle formulation for combined tumor therapy, designated as PDA@Mn-siSur-c-NPs, which comprises a polydopamine/manganese dioxide (PDA@MnO₂) core alongside survivin-targeting siRNA and cyclo(RGD-DPhe-K)-targeting moiety. Methods: The PDA@Mn-siSur-c-NPs were constructed and subjected to detailed characterization. [...] Read more.

Objective: This study aims to engineer a novel nanoparticle formulation for combined tumor therapy, designated as PDA@Mn-siSur-c-NPs, which comprises a polydopamine/manganese dioxide (PDA@MnO₂) core alongside survivin-targeting siRNA and cyclo(RGD-DPhe-K)-targeting moiety. Methods: The PDA@Mn-siSur-c-NPs were constructed and subjected to detailed characterization. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was employed to quantify manganese content. To assess siRNA stability within the system, samples were incubated with 50% fetal bovine serum (FBS) before agarose gel electrophoresis analysis. Additionally, cellular internalization by 4T1 cells and in vitro photothermal conversion efficiency of the formulation were evaluated. ICP-OES was further utilized to investigate the in vivo pharmacokinetics and tissue distribution of manganese. Animal model studies were conducted to assess the anti-breast cancer efficacy of PDA@Mn-siSur-c-NPs in combination with infrared irradiation. Results: The newly developed PDA@Mn-siSur-c-NPs demonstrated superior siRNA protection, reduced toxicity, and high photothermal conversion capacity. When combined with photothermal therapy (PTT), these nanoparticles exerted enhanced synergistic anti-tumor effects. Delivery of survivin siRNA resulted in a significant downregulation of survivin protein expression in tumor tissues. Moreover, magnetic resonance imaging (MRI) confirmed that the nanoparticles possess favorable imaging properties. Conclusions: This research demonstrates that the integration of PDA@Mn-siSur-c-NPs with PTT holds considerable therapeutic promise for improved breast cancer treatment. Full article

(This article belongs to the Special Issue Hybrid Nanoparticles for Cancer Therapy)

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16 pages, 3795 KB

Open AccessArticle

Two Drug–Drug Co-Amorphous Systems of Curcumin and Berberine Hydrochloride/Palmatine Hydrochloride with Improved Physicochemical Properties and Multifunctional Activities

by Yanjie Zhang, Quanhu Guo, Ling Liang, Mei Zhang, Rongjian Sa and Benyong Lou

Pharmaceutics 2026, 18(1), 9; https://doi.org/10.3390/pharmaceutics18010009 (registering DOI) - 20 Dec 2025

Abstract

Background/Objectives: The poor aqueous solubility of curcumin (CUR) limits its pharmaceutical application. Although amorphization can enhance its solubility, the amorphous form often exhibits insufficient physical stability. Co-amorphization, particularly drug–drug co-amorphous (CAM) formation, offers a promising approach to improve solubility, stability, and therapeutic [...] Read more.

Background/Objectives: The poor aqueous solubility of curcumin (CUR) limits its pharmaceutical application. Although amorphization can enhance its solubility, the amorphous form often exhibits insufficient physical stability. Co-amorphization, particularly drug–drug co-amorphous (CAM) formation, offers a promising approach to improve solubility, stability, and therapeutic efficacy. This study aimed to prepare and evaluate two CUR-based CAM systems using isoquinoline alkaloids berberine hydrochloride (BER) and palmatine hydrochloride (PAL) as co-formers to achieve simultaneous stabilization and synergistic bioactivity. Methods: CUR-BER and CUR-PAL CAM systems were prepared via rotary evaporation under vacuum at a 1:1 molar ratio. The solid-state properties were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscope (SEM), and ¹³C solid-state nuclear magnetic resonance spectroscopy (ssNMR). Dissolution, solubility, and stability studies were conducted, while antioxidant and anticancer activities were assessed by DPPH/ABTS⁺ radical-scavenging and MTT assays using HT-29 colorectal cancer cells. Results: PXRD and DSC confirmed the formation of single-phase amorphous systems with higher glass transition temperatures, indicating strong intermolecular interactions between CUR and BER/PAL. ¹³C ssNMR spectroscopy evidenced hydrogen-bond formation between the enolic hydroxyl moiety of CUR and the methoxy oxygen atoms in BER or PAL molecules. Both CAM systems significantly enhanced the solubility and dissolution rate of CUR, with CUR-PAL CAM showing up to a 15.1-fold solubility improvement. The CAM systems also displayed superior thermal stability, photolytic stability, and improved short-term humidity resistance, together with enhanced antioxidant and anticancer activities compared with pure amorphous CUR. Conclusions: Co-amorphization of CUR with isoquinoline alkaloids effectively improved solubility, stability, antioxidant and anticancer activities, representing a promising strategy for the rational design of multifunctional amorphous CUR-based drug formulations. Full article

(This article belongs to the Section Physical Pharmacy and Formulation)

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30 pages, 4266 KB

Open AccessArticle

The Impact of Vehicle Occlusivity on Skin Delivery and Activity of a Janus Kinase Inhibitor: Comparison of Oil-Based Formulations

by Paulo Sarango-Granda, Roya Mohammadi-Meyabadi, Antonio J. Braza, Lilian Sosa, Joaquim Suñer-Carbó, Mireia Mallandrich and Ana Cristina Calpena

Pharmaceutics 2026, 18(1), 8; https://doi.org/10.3390/pharmaceutics18010008 - 20 Dec 2025

Abstract

Background/Objectives: Baricitinib, a selective JAK1/JAK2 inhibitor, shows therapeutic potential in psoriasis; however, its oral use is associated with systemic adverse effects, encouraging the development of topical formulations. This study aimed at evaluating the influence of petrolatum type on the stability, biopharmaceutical performance, and [...] Read more.

Background/Objectives: Baricitinib, a selective JAK1/JAK2 inhibitor, shows therapeutic potential in psoriasis; however, its oral use is associated with systemic adverse effects, encouraging the development of topical formulations. This study aimed at evaluating the influence of petrolatum type on the stability, biopharmaceutical performance, and therapeutic activity of lipid-based formulations containing Baricitinib. Methods: Formulations were prepared with Labrafac^® Lipophile WL 1349 (L) and either liquid (LLV) or solid (LSV) petrolatum at 30% and 60% w/w. Stability, rheology, spreadability, in vitro release, ex vivo permeation, and skin retention were evaluated, along with the safety and efficacy in HET-CAM and imiquimod-induced psoriasis murine models. Results: Only 30% petrolatum formulations remained stable for 60 days. LLV exhibited Newtonian flow, higher spreadability, sustained release (83.7% at 50 h), and superior skin retention (94 µg/g of skin/cm²), whereas LSV showed pseudoplastic behavior, lower spreadability, and reduced release (47.4% at 50 h). Both formulations were non-irritant and improved stratum corneum hydration while reducing transepidermal water loss. In vivo, both reduced erythema, epidermal thickening, edema, and histological alterations, confirming anti-inflammatory efficacy. Conclusions: These results demonstrate that the vehicle occlusivity decisively modulates baricitinib’s release and activity. LLV formulation favored drug retention and enhanced permeation at 24 h. Overall, excipient selection is important in designing safe and effective topical JAK inhibitor formulations. Full article

(This article belongs to the Special Issue Skin Care Products for Healthy and Diseased Skin)

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17 pages, 2171 KB

Open AccessArticle

Targeting Redox Homeostasis and Cell Survival Signaling with a Flavonoid-Rich Extract of Bergamot Juice in In Vitro and In Vivo Colorectal Cancer Models

by Alessandro Maugeri, Paola De Cicco, Rebecca Amico, Martina Farina, Michele Navarra and Francesca Borrelli

Pharmaceutics 2026, 18(1), 7; https://doi.org/10.3390/pharmaceutics18010007 - 20 Dec 2025

Abstract

Background/Objectives: Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. Evidence suggests that a polyphenol-rich diet may lower the risk of CRC. The aim of this study was to demonstrate the potential antitumor effects of a flavonoid-rich extract [...] Read more.

Background/Objectives: Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. Evidence suggests that a polyphenol-rich diet may lower the risk of CRC. The aim of this study was to demonstrate the potential antitumor effects of a flavonoid-rich extract of bergamot juice (BJe) in both in vitro and in vivo CRC models, assessing the underlying mechanisms. Methods: CRC cells, among which HCT-116, have been employed to assess the fine mechanism of action of BJe, whereas a mouse model of azoxymethane (AOM)-induced CRC was exploited to appreciate the anti-cancer effects of BJe. Results: BJe inhibited the growth of several CRC cells, especially HCT-116. In this cell line, BJe induced apoptosis and blocked the cell cycle in the G1 phase, as well as modulated the gene expression of apoptosis- and cell cycle-related factors. Moreover, BJe prompted reactive oxygen species production and impaired mitochondrial membrane potential. In the nucleus of these cancerous cells, BJe induced DNA damage as confirmed by the raised levels of 8-oxo-2′-deoxyguanosine and phosphorylation of histone H2A.X. In mice with AOM-induced CRC, BJe was able to lower the number of aberrant crypt foci. Moreover, BJe reduced the percentage of mice bearing both polyps and tumors, as well as their number. Conclusions: Our study supports the role of BJe against CRC, providing knowledge on the underlying mechanism of action. Full article

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

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53 pages, 8086 KB

Open AccessReview

Pharmacological Management of Cancer Pain: Advances in Treatment Strategies and Drug Delivery Systems

by Xueying Yang, Rong Zhang, Aijia Wang, Dan Zhang, Jiangxue Cheng, Bingtao Zhai and Dongyan Guo

Pharmaceutics 2026, 18(1), 6; https://doi.org/10.3390/pharmaceutics18010006 - 20 Dec 2025

Abstract

Cancer pain seriously damages the quality of life of patients, and its management urgently needs new strategies with both efficacy and safety. This review deeply analyzes the clinical limitations of WHO’s third-order analgesic strategy in cancer pain management, especially emphasizes the unique value [...] Read more.

Cancer pain seriously damages the quality of life of patients, and its management urgently needs new strategies with both efficacy and safety. This review deeply analyzes the clinical limitations of WHO’s third-order analgesic strategy in cancer pain management, especially emphasizes the unique value of integrated traditional Chinese and Western medicine in synergy and reduction in adverse reactions, and summarizes the network interaction of related drugs through the regulation of multi-target analgesic mechanisms such as inflammatory factors, ion channels, neurotransmitters, and even glial cells and osteoclast activity in the tumor microenvironment. Building on this foundation, the article systematically analyzed the clinical advantages and limitations of drug delivery systems (DDS): oral sustained and controlled drug delivery system, mucosal drug delivery system (MDDS), transdermal drug delivery system (TDDS), and intrathecal targeted drug delivery (ITDD) in the treatment of cancer pain for the first time. The development prospects of new DDS: microneedles, disposable intrathecal drug delivery, and nano-drug delivery system (NDDS) in cancer pain were summarized in detail. Looking ahead, research into the analgesic mechanisms of drugs holds promise for providing a theoretical foundation for cancer pain management. Collaborative strategies integrating Chinese and Western medicine, coupled with precision delivery technologies, are expected to advance more efficient and safer pain control, offering new approaches and methods for achieving superior pain management outcomes. Full article

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

20 pages, 1978 KB

Open AccessArticle

Antibiofilm and Immunomodulatory Effects of Cinnamaldehyde in Corneal Epithelial Infection Models: Ocular Treatments Approach

by Ashraf Khalifa, Muthukumar Thangavelu, Krishnaraj Thirugnanasambantham and Hairul-Islam M. Ibrahim

Pharmaceutics 2026, 18(1), 5; https://doi.org/10.3390/pharmaceutics18010005 - 19 Dec 2025

Abstract

Background: Bacterial keratitis, a major cause of corneal blindness, is frequently associated with biofilm-forming pathogens such as Klebsiella pneumoniae. Cyclic-di-GMP (c-di-GMP) controls biofilm development, which increases antibiotic resistance and makes treatment more difficult, highlighting the need for innovative therapeutic approaches. Methods: [...] Read more.

Background: Bacterial keratitis, a major cause of corneal blindness, is frequently associated with biofilm-forming pathogens such as Klebsiella pneumoniae. Cyclic-di-GMP (c-di-GMP) controls biofilm development, which increases antibiotic resistance and makes treatment more difficult, highlighting the need for innovative therapeutic approaches. Methods: This study investigated cinnamaldehyde as a potential ocular therapeutic using combined computational and experimental approaches. Molecular docking and in vitro assays (XTT, resazurin reduction, crystal violet staining, qRT-PCR, and fluorescence microscopy) were used to evaluate the anti-biofilm and immunomodulatory activities of cinnamaldehyde (CA) against Klebsiella pneumoniae. Results: CA inhibited biofilm formation in a dose-dependent manner (≈89% at 1000 µM; >50% at 250 µM), reduced bacterial attachment to contact lenses, and downregulated key biofilm genes (mrkA, mrkC, ybtS, bolA). Docking analysis revealed strong binding affinity to the mrkH regulator (−5.46 kcal/mol. CA maintained more than 80% corneal cell viability by increasing IL-10, suppressing inflammatory mediators (IL-1β, IL-6, and TNF-α), and improving bacterial clearance. Conclusions: This study combines computational docking, biofilm quantification, immune cell assays, and functional gene expression analyses to reveal the ability of cinnamaldehyde not only to suppress biofilm formation but also to enhance macrophage-mediated clearance and modulate corneal immune responses, a multi-target approach not previously described in the context of bacterial keratitis. Such effects highlight its potential as a novel ocular drug candidate for protecting corneal integrity in infectious keratitis. Full article

(This article belongs to the Special Issue Ophthalmic Drug Delivery, 3rd Edition)

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