Pharmaceutics

24 pages, 1396 KiB

Open AccessArticle

Design of Experiments Leads to Scalable Analgesic Near-Infrared Fluorescent Coconut Nanoemulsions

by Amit Chandra Das, Gayathri Aparnasai Reddy, Shekh Md. Newaj, Smith Patel, Riddhi Vichare, Lu Liu and Jelena M. Janjic

Pharmaceutics 2025, 17(8), 1010; https://doi.org/10.3390/pharmaceutics17081010 (registering DOI) - 1 Aug 2025

Abstract

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription [...] Read more.

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

(This article belongs to the Special Issue Quality by Design in Pharmaceutical Manufacturing)

► Show Figures

Graphical abstract

35 pages, 1395 KiB

Open AccessReview

Local Chemotherapy of Skin Pre-Neoplastic Lesions and Malignancies from the Perspective of Current Pharmaceutics

by Nadezhda Ivanova

Pharmaceutics 2025, 17(8), 1009; https://doi.org/10.3390/pharmaceutics17081009 (registering DOI) - 1 Aug 2025

Abstract

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while [...] Read more.

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

(This article belongs to the Special Issue Lipid-Based Nanoparticulate Drug Delivery Systems: Preparation, Biomedical Applications, and Evaluation)

► Show Figures

Figure 1

16 pages, 1365 KiB

Open AccessArticle

Generation of Formates Following 20 kHz Sonication of DSPE-mPEG2000 PEGylated Phospholipid Micelles

by Perouza Parsamian and Paul Pantano

Pharmaceutics 2025, 17(8), 1008; https://doi.org/10.3390/pharmaceutics17081008 (registering DOI) - 1 Aug 2025

Abstract

Background: Previous research has demonstrated that 20 kHz probe or 37 kHz bath sonication of poloxamers comprising polypropylene glycol (PPG) and polyethylene glycol (PEG) blocks can generate degradation byproducts that are toxic to mammalian cells and organisms. Herein, an investigation of a [...] Read more.

Background: Previous research has demonstrated that 20 kHz probe or 37 kHz bath sonication of poloxamers comprising polypropylene glycol (PPG) and polyethylene glycol (PEG) blocks can generate degradation byproducts that are toxic to mammalian cells and organisms. Herein, an investigation of a PEGylated phospholipid micelle was undertaken to identify low-molecular-weight sonolytic degradation byproducts that could be cytotoxic. The concern here lies with the fact that sonication is a frequently employed step in drug delivery manufacturing processes, during which PEGylated phospholipids can be subjected to shear forces and other extreme oxidative and thermal conditions. Methods: Control and 20 kHz-sonicated micelles of DSPE-mPEG2000 were analyzed using dynamic light scattering (DLS) and zeta potential analyses to study colloidal properties, matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) mass spectroscopy (MS) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy to study the structural integrity of DSPE-mPEG2000, and ¹H-NMR spectroscopy and high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection to quantitate the formation of low-molecular-weight degradation byproducts. Results: MALDI-TOF-MS analyses of 20 kHz-sonicated DSPE-mPEG2000 revealed the loss of ethylene glycol moieties in accordance with depolymerization of the PEG chain; ¹H-NMR spectroscopy showed the presence of formate, a known oxidative/thermal degradation product of PEG; and HPLC-UV showed that the generation of formate was dependent on 20 kHz probe sonication time between 5 and 60 min. Conclusions: It was found that 20 kHz sonication can degrade the PEG chain of DSPE-mPEG2000, altering the micelle’s PEG corona and generating formate, a known ocular toxicant. Full article

(This article belongs to the Special Issue Lipid-Based Nanoparticulate Drug Delivery Systems: Preparation, Biomedical Applications, and Evaluation)

► Show Figures

Figure 1

26 pages, 89199 KiB

Open AccessArticle

Light-Responsive PLGA Microparticles for On-Demand Vancomycin Release and Enhanced Antibacterial Efficiency

by Mishal Pokharel, Abid Neron, Amit Kumar Dey, Aishwarya Raksha Siddharthan, Menaka Konara, Md Mainuddin Sagar, Tracie Ferreira and Kihan Park

Pharmaceutics 2025, 17(8), 1007; https://doi.org/10.3390/pharmaceutics17081007 - 1 Aug 2025

Abstract

Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) [...] Read more.

Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) designed for the sustained release of vancomycin hydrochloride. Methods: The MPs were co-loaded with indocyanine green (ICG), a near-infrared (NIR) responsive agent, and fabricated via the double emulsion method.They were characterized for stability, surface modification, biocompatibility, and antibacterial efficacy. Results: Dynamic light scattering and zeta potential analyses confirmed significant increases in particle size and surface charge reversal following chitosan coating. Scanning electron microscopy revealed uniform morphology in uncoated MPs (1–10

μ

m) and irregular surfaces post-coating. Stability tests demonstrated drug retention for up to 180 days. Among formulations, PVI1 exhibited the highest yield (76.67 ± 1.3%) and encapsulation efficiency (56.2 ± 1.95%). NIR irradiation (808 nm) enhanced drug release kinetics, with formulation PVI4 achieving over 48.9% release, resulting in improved antibacterial activity. Chitosan-coated MPs (e.g., PVI4-C) effectively suppressed drug release without NIR light for up to 8 h, with cumulative release reaching only 10.89%. Without NIR light, bacterial colonies exceeded 1000 CFU; NIR-triggered release reduced them below 120 CFU. Drug release data fitted best with the zero-order and Korsmeyer–Peppas models, suggesting a combination of diffusion-controlled and constant-rate release behavior. Conclusions: These results demonstrate the promise of chitosan-coated NIR-responsive PLGA MPs for precise, on-demand antibiotic delivery and improved antibacterial performance. Full article

(This article belongs to the Special Issue Nano-Based Delivery Systems for Topical Applications)

► Show Figures

Figure 1

17 pages, 1353 KiB

Open AccessArticle

Inhibition of Human Coronavirus 229E by Lactoferrin-Derived Peptidomimetics

by Maria Carmina Scala, Magda Marchetti, Martina Landi, Marialuigia Fantacuzzi, Fabiana Superti, Mariangela Agamennone, Pietro Campiglia and Marina Sala

Pharmaceutics 2025, 17(8), 1006; https://doi.org/10.3390/pharmaceutics17081006 - 1 Aug 2025

Abstract

Background/Objectives: Viral respiratory infections have a significant impact on global health and the economy. While vaccines are effective in preventing infection, they might not be available or sufficient when used alone and must be complemented by specific therapeutic strategies. The development of new [...] Read more.

Background/Objectives: Viral respiratory infections have a significant impact on global health and the economy. While vaccines are effective in preventing infection, they might not be available or sufficient when used alone and must be complemented by specific therapeutic strategies. The development of new antiviral agents is increasingly important due to the continual emergence of novel respiratory pathogens. Previously we identified bovine lactoferrin (bLf)-derived tetrapeptides and peptidomimetics that showed potent in vitro activity against the influenza A virus in the picomolar range. Methods: Inspired by these results, in this study, we evaluated the antiviral potential of these compounds against HCoV-229E, a human coronavirus that can cause severe disease in immunocompromised individuals, using a compound repositioning approach. Results: Functional studies revealed that SK(N-Me)HS (3) interferes with viral entry and replication, while compound SNKHS (5) primarily blocks infection in the early stages. Biophysical analyses confirmed the occurrence of high-affinity binding to the viral spike protein, and computational studies suggested that the compounds target a region involved in conformational changes necessary for membrane fusion. Conclusions: These findings highlight these compounds as promising candidates for coronavirus entry inhibition and underscore the value of compound repurposing in antiviral development. Full article

(This article belongs to the Special Issue Peptides-Based Antiviral Agents)

► Show Figures

Figure 1

48 pages, 1188 KiB

Open AccessReview

Extemporaneous Compounding, Pharmacy Preparations and Related Product Care in the Netherlands

by Herman J. Woerdenbag, Boy van Basten, Christien Oussoren, Oscar S. N. M. Smeets, Astrid Annaciri-Donkers, Mirjam Crul, J. Marina Maurer, Kirsten J. M. Schimmel, E. Marleen Kemper, Marjolijn N. Lub-de Hooge, Nanno Schreuder, Melissa Eikmann, Arwin S. Ramcharan, Richard B. Lantink, Julian Quodbach, Hendrikus H. Boersma, Oscar Kelder, Karin H. M. Larmené-Beld, Paul P. H. Le Brun, Robbert Jan Kok, Reinout C. A. Schellekens, Oscar Breukels, Henderik W. Frijlink and Bahez Gareb Show full author list Hide full author list

Pharmaceutics 2025, 17(8), 1005; https://doi.org/10.3390/pharmaceutics17081005 - 31 Jul 2025

Abstract

Background/Objectives: In many parts of the world, pharmacists hold the primary responsibility for providing safe and effective pharmacotherapy. A key aspect is the availability of appropriate medicines for each individual patient. When industrially manufactured medicines are unsuitable or unavailable, pharmacists can prepare [...] Read more.

Background/Objectives: In many parts of the world, pharmacists hold the primary responsibility for providing safe and effective pharmacotherapy. A key aspect is the availability of appropriate medicines for each individual patient. When industrially manufactured medicines are unsuitable or unavailable, pharmacists can prepare tailor-made medicines. While this principle applies globally, practices vary between countries. In the Netherlands, the preparation of medicines in pharmacies is well-established and integrated into routine healthcare. This narrative review explores the role and significance of extemporaneous compounding, pharmacy preparations and related product care in the Netherlands. Methods: Pharmacists involved in pharmacy preparations across various professional sectors, including community and hospital pharmacies, central compounding facilities, academia, and the professional pharmacists’ organisation, provided detailed and expert insights based on the literature and policy documents while also sharing their critical perspectives. Results: We present arguments supporting the need for pharmacy preparations and examine their position and role in community and hospital pharmacies in the Netherlands. Additional topics are discussed, including the regulatory and legal framework, outsourcing, quality assurance, standardisation, education, and international context. Specific pharmacy preparation topics, often with a research component and a strong focus on product care, are highlighted, including paediatric dosage forms, swallowing difficulties and feeding tubes, hospital-at-home care, reconstitution of oncolytic drugs and biologicals, total parenteral nutrition (TPN), advanced therapy medicinal products (ATMPs), radiopharmaceuticals and optical tracers, clinical trial medication, robotisation in reconstitution, and patient-centric solid oral dosage forms. Conclusions: The widespread acceptance of pharmacy preparations in the Netherlands is the result of a unique combination of strict adherence to tailored regulations that ensure quality and safety, and patient-oriented flexibility in design, formulation, and production. This approach is further reinforced by the standardisation of a broad range of formulations and procedures across primary, secondary and tertiary care, as well as by continuous research-driven innovation to develop new medicines, formulations, and production methods. Full article

(This article belongs to the Special Issue Extemporaneous Formulations: Filling the Gap in the Pharmaceutical Industry with Personalized Medicines)

8 pages, 212 KiB

Open AccessCommunication

Retrospective Evaluation of L-Acetyl Carnitine and Palmitoylethanolamide as Add-On Therapy in Patients with Fibromyalgia and Small Fiber Neuropathy

by Crescenzio Bentivenga, Arrigo Francesco Giuseppe Cicero, Federica Fogacci, Natalia Evangelia Politi, Antonio Di Micoli, Eugenio Roberto Cosentino, Paolo Gionchetti and Claudio Borghi

Pharmaceutics 2025, 17(8), 1004; https://doi.org/10.3390/pharmaceutics17081004 - 31 Jul 2025

Abstract

Fibromyalgia is a complex disorder characterized by chronic widespread pain and a variety of related symptoms. Growing evidence suggests that the central and peripheral nervous systems are involved, with small fiber neuropathy playing a key role in its development. We retrospectively reviewed the [...] Read more.

Fibromyalgia is a complex disorder characterized by chronic widespread pain and a variety of related symptoms. Growing evidence suggests that the central and peripheral nervous systems are involved, with small fiber neuropathy playing a key role in its development. We retrospectively reviewed the medical records of 100 patients diagnosed with primary fibromyalgia. Those showing symptoms indicative of small fiber dysfunction who were treated with L-Acetyl Carnitine (LAC) and Palmitoylethanolamide (PEA) alongside standard care (SOC) were compared to matched controls who received only SOC. To ensure comparable groups, propensity score matching was used. Changes in Fibromyalgia Impact Questionnaire Revised (FIQR) scores over 12 weeks were analyzed using non-parametric tests due to the data’s non-normal distribution. After matching, 86 patients (43 in each group) were included. The group receiving LAC and PEA as add-on therapy experienced a significant median reduction in FIQR scores (−19.0 points, p < 0.001), while the SOC-only group showed no significant change. Comparisons between groups confirmed that the improvement was significantly greater in the LAC+PEA group (p < 0.001). These results suggest that adding LAC and PEA to standard care may provide meaningful symptom relief for fibromyalgia patients with suspected small fiber involvement. This supports the hypothesis that peripheral nervous system dysfunction contributes to the disease burden in this subgroup. However, further prospective controlled studies are needed to confirm these promising findings. Full article

(This article belongs to the Special Issue Emerging Drugs and Formulations for Pain Treatment)

24 pages, 7421 KiB

Open AccessArticle

Pristimerin Dampens Acetaminophen-Induced Hepatotoxicity; The Role of NF-κB/iNOS/COX-II/Cytokines, PI3K/AKT, and BAX/BCL-2/Caspase-3 Signaling Pathways

by Mohammed A. Altowijri, Marwa E. Abdelmageed, Randa El-Gamal, Tahani Saeedi and Dina S. El-Agamy

Pharmaceutics 2025, 17(8), 1003; https://doi.org/10.3390/pharmaceutics17081003 - 31 Jul 2025

Abstract

Background: Acetaminophen (APAP) is a popular and safe pain reliever. Due to its widespread availability, it is commonly implicated in intentional or unintentional overdoses, which result in severe liver impairment. Pristimerin (Prist) is a natural triterpenoid that has potent antioxidant and anti-inflammatory properties. [...] Read more.

Background: Acetaminophen (APAP) is a popular and safe pain reliever. Due to its widespread availability, it is commonly implicated in intentional or unintentional overdoses, which result in severe liver impairment. Pristimerin (Prist) is a natural triterpenoid that has potent antioxidant and anti-inflammatory properties. Our goal was to explore the protective effects of Prist against APAP-induced acute liver damage. Method: Mice were divided into six groups: control, Prist control, N-acetylcysteine (NAC) + APAP, APAP, and two Prist + APAP groups. Prist (0.4 and 0.8 mg/kg) was given for five days and APAP on day 5. Liver and blood samples were taken 24 h after APAP administration and submitted for different biochemical and molecular assessments. Results: Prist counteracted APAP-induced acute liver damage, as it decreased general liver dysfunction biomarkers, and attenuated APAP-induced histopathological lesions. Prist decreased oxidative stress and enforced hepatic antioxidants. Notably, Prist significantly reduced the genetic and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-II), p-phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (p-AKT), and the inflammatory cytokines: nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins-(IL-6 and IL-1β) in hepatic tissues. Additionally, the m-RNA and protein levels of the apoptotic Bcl2-associated X protein (BAX) and caspase-3 were lowered and the anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) was increased upon Prist administration. Conclusion: Prist ameliorated APAP-induced liver injury in mice via its potent anti-inflammatory/antioxidative and anti-apoptotic activities. These effects were mediated through modulation of NF-κB/iNOS/COX-II/cytokines, PI3K/AKT, and BAX/BCL-2/caspase-3 signaling pathways. Full article

(This article belongs to the Section Drug Targeting and Design)

► Show Figures

Figure 1

58 pages, 681 KiB

Open AccessReview

In Silico ADME Methods Used in the Evaluation of Natural Products

by Robert Ancuceanu, Beatrice Elena Lascu, Doina Drăgănescu and Mihaela Dinu

Pharmaceutics 2025, 17(8), 1002; https://doi.org/10.3390/pharmaceutics17081002 - 31 Jul 2025

Abstract

The pharmaceutical industry faces significant challenges when promising drug candidates fail during development due to suboptimal ADME (absorption, distribution, metabolism, excretion) properties or toxicity concerns. Natural compounds are subject to the same pharmacokinetic considerations. In silico approaches offer a compelling advantage—they eliminate the [...] Read more.

The pharmaceutical industry faces significant challenges when promising drug candidates fail during development due to suboptimal ADME (absorption, distribution, metabolism, excretion) properties or toxicity concerns. Natural compounds are subject to the same pharmacokinetic considerations. In silico approaches offer a compelling advantage—they eliminate the need for physical samples and laboratory facilities, while providing rapid and cost-effective alternatives to expensive and time-consuming experimental testing. Computational methods can often effectively address common challenges associated with natural compounds, such as chemical instability and poor solubility. Through a review of the relevant scientific literature, we present a comprehensive analysis of in silico methods and tools used for ADME prediction, specifically examining their application to natural compounds. Whereas we focus on identifying the predominant computational approaches applicable to natural compounds, these tools were developed for conventional drug discovery and are of general use. We examine an array of computational approaches for evaluating natural compounds, including fundamental methods like quantum mechanics calculations, molecular docking, and pharmacophore modeling, as well as more complex techniques such as QSAR analysis, molecular dynamics simulations, and PBPK modeling. Full article

(This article belongs to the Special Issue Advanced In Silico Methods and Digital Platforms for the Prediction of ADMET and Pharmacokinetics Properties)

2 pages, 1081 KiB

Open AccessCorrection

Correction: Khalid et al. Development of Rapidly Dissolving Microneedles Integrated with Valsartan-Loaded Nanoliposomes for Transdermal Drug Delivery: In Vitro and Ex Vivo Evaluation. Pharmaceutics 2025, 17, 483

by Ramsha Khalid, Syed Mahmood, Zarif Mohamed Sofian, Zamri Chik and Yi Ge

Pharmaceutics 2025, 17(8), 1001; https://doi.org/10.3390/pharmaceutics17081001 - 31 Jul 2025

Abstract

In the original publication [...] Full article

► Show Figures

Figure 1

20 pages, 2382 KiB

Open AccessArticle

The Impact of the Injected Mass of the Gastrin-Releasing Peptide Receptor Antagonist on Uptake in Breast Cancer: Lessons from a Phase I Trial of [^99mTc]Tc-DB8

by Olga Bragina, Vladimir Chernov, Mariia Larkina, Ruslan Varvashenya, Roman Zelchan, Anna Medvedeva, Anastasiya Ivanova, Liubov Tashireva, Theodosia Maina, Berthold A. Nock, Panagiotis Kanellopoulos, Jens Sörensen, Anna Orlova and Vladimir Tolmachev

Pharmaceutics 2025, 17(8), 1000; https://doi.org/10.3390/pharmaceutics17081000 - 31 Jul 2025

Abstract

Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific [...] Read more.

Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific probes for SPECT would permit imaging-guided therapy in regions with restricted access to PET facilities. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the [^99mTc]Tc-DB8 GRPR-antagonistic peptide. We also addressed the important issue of finding the optimal injected peptide mass. Methods: Fifteen female patients with ER-positive primary breast cancer were enrolled and divided into three cohorts receiving [^99mTc]Tc-DB8 (corresponding to three distinct doses of 40, 80, or 120 µg DB8) comprising five patients each. Additionally, four patients with ER-negative primary tumors were injected with 80 µg [^99mTc]Tc-DB8. The injected activity was 360 ± 70 MBq. Planar scintigraphy was performed after 2, 4, 6, and 24 h, and SPECT/CT scans followed planar imaging 2, 4, and 6 h after injection. Results: No adverse events were associated with [^99mTc]Tc-DB8 injections. The effective dose was 0.009–0.014 mSv/MBq. Primary tumors and all known lymph node metastases were visualized irrespective of injected peptide mass. The highest uptake in the ER-positive tumors was 2 h after injection of [^99mTc]Tc-DB8 at a 80 µg DB8 dose (SUV_max 5.3 ± 1.2). Injection of [^99mTc]Tc-DB8 with 80 µg DB8 provided significantly (p < 0.01) higher uptake in primary ER-positive breast cancer lesions than injection with 40 µg DB8 (SUV_max 2.0 ± 0.3) or 120 µg (SUV_max 3.2 ± 1.4). Tumor-to-contralateral breast ratio after injection of 80 μg was also significantly (p < 0.01, ANOVA test) higher than ratios after injection of other peptide masses. The uptake in ER-negative lesions was significantly lower (SUV_max 2.0 ± 0.3) than in ER-positive tumors. Conclusions: Imaging using [^99mTc]Tc-DB8 is safe, tolerable, and associated with low absorbed doses. The tumor uptake is dependent on the injected peptide mass. The injection of an optimal mass (80 µg) provides the highest uptake in ER-positive tumors. At optimal dosing, the uptake was significantly higher in ER-positive than in ER-negative lesions. Full article

(This article belongs to the Special Issue Advances in Radiopharmaceuticals: Enhancing Targeted Delivery, Disease Diagnosis, and Therapeutic Applications)

► Show Figures

Graphical abstract

13 pages, 1413 KiB

Open AccessSystematic Review

The Efficacy of Solanezumab in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Clinical Trials

by Mathias S. Renteros, Renzo Barreto-Abanto, Diego C. Huapaya, Mateo Tovar-Cobos, Richard D. Alvarado-Ramos, Oriana Rivera-Lozada and Joshuan J. Barboza

Pharmaceutics 2025, 17(8), 999; https://doi.org/10.3390/pharmaceutics17080999 (registering DOI) - 31 Jul 2025

Abstract

Background/Objectives: Solanezumab is a humanized monoclonal antibody designed to bind soluble amyloid-beta (Aβ) and facilitate its clearance from the brain, aiming to slow the progression of Alzheimer’s disease (AD). Methods: A systematic search was applied in four medical databases through October 2024 [...] Read more.

Background/Objectives: Solanezumab is a humanized monoclonal antibody designed to bind soluble amyloid-beta (Aβ) and facilitate its clearance from the brain, aiming to slow the progression of Alzheimer’s disease (AD). Methods: A systematic search was applied in four medical databases through October 2024 to identify phase 2 or 3 randomized controlled trials evaluating solanezumab in patients aged ≥50 years with mild AD or in preclinical stages. The primary outcomes were changes in cognitive and functional scales, including ADAS-cog14, MMSE, ADCS-ADL, and CDR-SB. Data were pooled using a random-effects model, and certainty of evidence was assessed using GRADE. Results: Seven trials involving 4181 participants were included. Solanezumab did not significantly reduce cognitive decline based on ADAS-cog14 (MD = −0.75; 95% CI: −2.65 to 1.15; very low certainty) or improve functional scores on ADCS-ADL (MD = 0.85; 95% CI: −1.86 to 3.56; very low certainty) and CDR-SB (MD = −0.15; 95% CI: −0.89 to 0.60; very low certainty). A modest but statistically significant improvement was observed in MMSE scores (MD = 0.59; 95% CI: 0.33 to 0.86; moderate certainty). Conclusions: While solanezumab may offer slight benefits in general cognitive performance, its overall impact on clinically meaningful outcomes remains limited. The results do not support its use as a disease-modifying therapy for Alzheimer’s disease in either preclinical or symptomatic stages. Full article

(This article belongs to the Special Issue New Trends in the Controlled Release Systems of Medicinal Substances Used in the Treatment of Diseases of the Central Nervous System)

► Show Figures

Figure 1

22 pages, 5738 KiB

Open AccessArticle

Effect of Solute Concentration and Filtration Rate on the Scale Production of a Physically Stable Amorphous Solid Form of Nilotinib

by Zhihui Yuan, Bowen Zhang, Asad Nawaz and Zunhua Li

Pharmaceutics 2025, 17(8), 998; https://doi.org/10.3390/pharmaceutics17080998 (registering DOI) - 31 Jul 2025

Abstract

Background/Objectives: Amorphous solid drugs exhibit physical instability and a propensity for crystallization, which leads to reduced solubility and bioavailability. Hence, this study optimized scale manufacturing parameters for producing a physically stable amorphous solid form of nilotinib using neutralization precipitation. Methods: A systematic evaluation [...] Read more.

Background/Objectives: Amorphous solid drugs exhibit physical instability and a propensity for crystallization, which leads to reduced solubility and bioavailability. Hence, this study optimized scale manufacturing parameters for producing a physically stable amorphous solid form of nilotinib using neutralization precipitation. Methods: A systematic evaluation of the effects of the solute concentration and filtration rate on amorphous physical stability was conducted using the pair distribution function (PDF), principal component analysis (PCA), and reduced crystallization temperature (R_c) values. Results: It showed concentration-dependent crystallization resistance, with optimal physical stability achieved at a solute concentration of 0.126 mol/L and a 124 mL/min filtration rate. Experiments carried out at a scale of 50 g confirmed the stability of the production process. Conclusions: These findings provide a validated framework for developing lab-scale amorphous drug products with improved shelf-life stability, assessed using indirect indicators (PDF, R_c) and confirmed through accelerated stability tests. Full article

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

► Show Figures

Graphical abstract

17 pages, 2562 KiB

Open AccessArticle

Comparative Stability and Anesthetic Evaluation of Holy Basil Essential Oil Formulated in SNEDDS and Microemulsion Systems in Cyprinus carpio var. Koi

by Kantaporn Kheawfu, Chuda Chittasupho, Surachai Pikulkaew, Wasana Chaisri and Taepin Junmahasathien

Pharmaceutics 2025, 17(8), 997; https://doi.org/10.3390/pharmaceutics17080997 (registering DOI) - 31 Jul 2025

Abstract

Background/Objectives: Holy basil (Ocimum tenuiflorum L.) essential oil exhibits antioxidant, antimicrobial, and anesthetic activities, mainly due to eugenol, methyl eugenol, and β-caryophyllene. However, its clinical application is limited by poor water solubility, instability, and low bioavailability. This study developed and compared two [...] Read more.

Background/Objectives: Holy basil (Ocimum tenuiflorum L.) essential oil exhibits antioxidant, antimicrobial, and anesthetic activities, mainly due to eugenol, methyl eugenol, and β-caryophyllene. However, its clinical application is limited by poor water solubility, instability, and low bioavailability. This study developed and compared two delivery systems, self-nanoemulsifying drug delivery systems (SNEDDS) and microemulsions (ME), to enhance their stability and fish anesthetic efficacy. Methods: The optimized SNEDDS (25% basil oil, 8.33% coconut oil, 54.76% Tween 80, 11.91% PEG 400) and ME (12% basil oil, 32% Tween 80, 4% sorbitol, 12% ethanol, 40% water) were characterized for droplet size, PDI, zeta potential, pH, and viscosity. Stability was evaluated by monitoring droplet size and PDI over time and by determining the retention of eugenol, methyl eugenol, and β-caryophyllene after storage at 45 °C. Fish anesthetic efficacy was tested in koi carp (Cyprinus carpio var. koi). Results: SNEDDS maintained a small droplet size (~22.78 ± 1.99 nm) and low PDI (0.188 ± 0.088 at day 60), while ME showed significant size enlargement (up to 177.10 ± 47.50 nm) and high PDI (>0.5). After 90 days at 45 °C, SNEDDS retained 94.45% eugenol, 94.08% methyl eugenol, and 88.55% β-caryophyllene, while ME preserved 104.76%, 103.53%, and 94.47%, respectively. In vivo testing showed that SNEDDS achieved faster anesthesia (114.70 ± 24.80 s at 120 ppm) and shorter recovery (379.60 ± 15.61 s) than ME (134.90 ± 4.70 s; 473.80 ± 16.94 s). Ethanol failed to induce anesthesia at 40 ppm and performed poorly compared to SNEDDS and ME at other concentrations (p < 0.0001). Conclusions: SNEDDS demonstrated superior physical stability and fish anesthetic performance compared to ME. These findings support SNEDDS as a promising formulation for delivering holy basil essential oil in biomedical and aquaculture applications. Full article

(This article belongs to the Special Issue Applications of Nanotechnology in Veterinary Drug Delivery)

► Show Figures

Figure 1

29 pages, 2636 KiB

Open AccessReview

Inhalable Nanomaterial Discoveries for Lung Cancer Therapy: A Review

by Iqra Safdar, Syed Mahmood, Muhammad Kumayl Abdulwahab, Suzita Mohd Noor, Yi Ge and Zarif Mohamed Sofian

Pharmaceutics 2025, 17(8), 996; https://doi.org/10.3390/pharmaceutics17080996 (registering DOI) - 31 Jul 2025

Abstract

Lung cancer remains one of the most common and deadliest forms of cancer worldwide despite notable advancements in its management. Conventional treatments, such as chemotherapy, often have limitations in effectively targeting cancer cells, which frequently lead to off-target side effects. In this context, [...] Read more.

Lung cancer remains one of the most common and deadliest forms of cancer worldwide despite notable advancements in its management. Conventional treatments, such as chemotherapy, often have limitations in effectively targeting cancer cells, which frequently lead to off-target side effects. In this context, the pulmonary delivery of inhalable nanomaterials offers the advantages of being rapid, efficient, and target-specific, with minimal systemic side effects. This concise review summarizes the basic research and clinical translation of inhalable nanomaterials for the treatment of lung cancer. We also provide insights into the latest advances in pulmonary drug delivery systems, focusing on various types of pulmonary devices and nanomaterials. Furthermore, this paper discusses significant challenges in translating the discoveries of inhalable nanomaterials into clinical care for lung cancer and shares strategies to overcome these issues. Full article

(This article belongs to the Special Issue Lipid-Based Nanoparticulate Drug Delivery Systems: Preparation, Biomedical Applications, and Evaluation)

► Show Figures

Graphical abstract

13 pages, 1321 KiB

Open AccessArticle

Intravitreal Povidone-Iodine Injection and Low-Dose Antibiotic Irrigation for Infectious Endophthalmitis: A Retrospective Case Series

by Yumiko Machida, Hiroyuki Nakashizuka, Hajime Onoe, Yorihisa Kitagawa, Naoya Nakagawa, Keisuke Miyata, Misato Yamakawa, Yu Wakatsuki, Koji Tanaka, Ryusaburo Mori and Hiroyuki Shimada

Pharmaceutics 2025, 17(8), 995; https://doi.org/10.3390/pharmaceutics17080995 (registering DOI) - 31 Jul 2025

Abstract

Background/Objectives: Infectious endophthalmitis is a vision-threatening complication of intraocular surgery and intravitreal injections. Standard treatment involves intravitreal antibiotics; however, concerns regarding multidrug resistance and vancomycin-associated hemorrhagic occlusive retinal vasculitis (HORV) highlight the need for alternative antimicrobial strategies. This study aimed to evaluate the [...] Read more.

Background/Objectives: Infectious endophthalmitis is a vision-threatening complication of intraocular surgery and intravitreal injections. Standard treatment involves intravitreal antibiotics; however, concerns regarding multidrug resistance and vancomycin-associated hemorrhagic occlusive retinal vasculitis (HORV) highlight the need for alternative antimicrobial strategies. This study aimed to evaluate the clinical efficacy and safety of a protocol combining intravitreal injection of 1.25% povidone-iodine (PI) with intraoperative irrigation using low concentrations of vancomycin and ceftazidime. Methods: We retrospectively analyzed 11 eyes from patients diagnosed with postoperative or injection-related endophthalmitis. Six of the eleven cases received an initial intravitreal injection of 1.25% PI, followed by pars plana vitrectomy with irrigation using balanced salt solution PLUS containing vancomycin (20 μg/mL) and ceftazidime (40 μg/mL). A second intravitreal PI injection was administered at the end of surgery in all cases. Additional PI injections were administered postoperatively based on clinical response. Clinical outcomes included best-corrected visual acuity (BCVA), microbial culture results, corneal endothelial cell density, and visual field testing. Results: All eyes achieved complete infection resolution without recurrence. The mean BCVA improved significantly from 2.18 logMAR at baseline to 0.296 logMAR at final follow-up (p < 0.001). No adverse events were observed on specular microscopy or visual field assessment. The protocol was well tolerated, and repeated PI injections showed no signs of ocular toxicity. Conclusions: This combination protocol provides a safe and effective treatment strategy for infectious endophthalmitis. It enables rapid and complete infection resolution while minimizing the risks associated with intravitreal antibiotics. These findings support further investigation of this protocol as a practical and globally accessible alternative to standard intravitreal antimicrobial therapy. Full article

(This article belongs to the Special Issue Drug Delivery Systems for Ocular Diseases)

► Show Figures

Graphical abstract

2 pages, 130 KiB

Open AccessCorrection

Correction: Domingues et al. Pediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies. Pharmaceutics 2023, 15, 2431

by Cátia Domingues, Ivana Jarak, Francisco Veiga, Marília Dourado and Ana Figueiras

Pharmaceutics 2025, 17(8), 994; https://doi.org/10.3390/pharmaceutics17080994 (registering DOI) - 31 Jul 2025

Abstract

There were some aspects in the original publication that need to be corrected [...] Full article

18 pages, 2263 KiB

Open AccessArticle

Predicting Antimicrobial Peptide Activity: A Machine Learning-Based Quantitative Structure–Activity Relationship Approach

by Eliezer I. Bonifacio-Velez de Villa, María E. Montoya-Alfaro, Luisa P. Negrón-Ballarte and Christian Solis-Calero

Pharmaceutics 2025, 17(8), 993; https://doi.org/10.3390/pharmaceutics17080993 (registering DOI) - 31 Jul 2025

Abstract

Background: Peptides are a class of molecules that can be presented as good antimicrobials and with mechanisms that avoid resistance, and the design of peptides with good activity can be complex and laborious. The study of their quantitative structure–activity relationships through machine [...] Read more.

Background: Peptides are a class of molecules that can be presented as good antimicrobials and with mechanisms that avoid resistance, and the design of peptides with good activity can be complex and laborious. The study of their quantitative structure–activity relationships through machine learning algorithms can shed light on a rational and effective design. Methods: Information on the antimicrobial activity of peptides was collected, and their structures were characterized by molecular descriptors generation to design regression and classification models based on machine learning algorithms. The contribution of each descriptor in the generated models was evaluated by determining its relative importance and, finally, the antimicrobial activity of new peptides was estimated. Results: A structured database of antimicrobial peptides and their descriptors was obtained, with which 56 machine learning models were generated. Random Forest-based models showed better performance, and of these, regression models showed variable performance (R² = 0.339–0.574), while classification models showed good performance (MCC = 0.662–0.755 and ACC = 0.831–0.877). Those models based on bacterial groups showed better performance than those based on the entire dataset. The properties of the new peptides generated are related to important descriptors that encode physicochemical properties such as lower molecular weight, higher charge, propensity to form alpha-helical structures, lower hydrophobicity, and higher frequency of amino acids such as lysine and serine. Conclusions: Machine learning models allowed to establish the structure–activity relationships of antimicrobial peptides. Classification models performed better than regression models. These models allowed us to make predictions and new peptides with high antimicrobial potential were proposed. Full article

(This article belongs to the Special Issue Advances in Bioactive Peptides from Natural Sources: Characterization, Biological Targets and Promising Applications)

► Show Figures

Graphical abstract

31 pages, 2007 KiB

Open AccessReview

Artificial Intelligence-Driven Strategies for Targeted Delivery and Enhanced Stability of RNA-Based Lipid Nanoparticle Cancer Vaccines

by Ripesh Bhujel, Viktoria Enkmann, Hannes Burgstaller and Ravi Maharjan

Pharmaceutics 2025, 17(8), 992; https://doi.org/10.3390/pharmaceutics17080992 - 30 Jul 2025

Abstract

The convergence of artificial intelligence (AI) and nanomedicine has transformed cancer vaccine development, particularly in optimizing RNA-loaded lipid nanoparticles (LNPs). Stability and targeted delivery are major obstacles to the clinical translation of promising RNA-LNP vaccines for cancer immunotherapy. This systematic review analyzes the [...] Read more.

The convergence of artificial intelligence (AI) and nanomedicine has transformed cancer vaccine development, particularly in optimizing RNA-loaded lipid nanoparticles (LNPs). Stability and targeted delivery are major obstacles to the clinical translation of promising RNA-LNP vaccines for cancer immunotherapy. This systematic review analyzes the AI’s impact on LNP engineering through machine learning-driven predictive models, generative adversarial networks (GANs) for novel lipid design, and neural network-enhanced biodistribution prediction. AI reduces the therapeutic development timeline through accelerated virtual screening of millions of lipid combinations, compared to conventional high-throughput screening. Furthermore, AI-optimized LNPs demonstrate improved tumor targeting. GAN-generated lipids show structural novelty while maintaining higher encapsulation efficiency; graph neural networks predict RNA-LNP binding affinity with high accuracy vs. experimental data; digital twins reduce lyophilization optimization from years to months; and federated learning models enable multi-institutional data sharing. We propose a framework to address key technical challenges: training data quality (min. 15,000 lipid structures), model interpretability (SHAP > 0.65), and regulatory compliance (21CFR Part 11). AI integration reduces manufacturing costs and makes personalized cancer vaccine affordable. Future directions need to prioritize quantum machine learning for stability prediction and edge computing for real-time formulation modifications. Full article

(This article belongs to the Special Issue Recent Advances in the Development, Characterization, and Stability Aspects of RNA-Based Vaccines)

► Show Figures

Figure 1

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