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  • New
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  • Research Article
  • 10.3390/pharmaceutics17111386
Anti-Hyperpigmentation-Related Potential Activities in B16BL6 Cells and Chemical Composition of Essential Oil from Chamaecyparis pisifera Leaves
  • Oct 25, 2025
  • Pharmaceutics
  • Do Yoon Kim + 4 more

Background/Objectives: Chamaecyparis pisifera (C. pisifera; family Cupressaceae) is known to have insecticidal and antibacterial activities, but its effects on skin depigmentation-related activities have not been elucidated. Thus, in the present study, we aimed to investigate the anti-hyperpigmentation potential of C. pisifera var. filifera leaf essential oil (CPEO), specially focusing on responses related to melanogenesis and melanin transport, using B16BL6 cells. Methods: CPEO was extracted by steam distillation, and its composition was determined by GC/MS spectrometry. The biological activities of CPEO on B16BL6 melanoma cells were analyzed using the water soluble tetrazolium salt, BrdU incorporation, ELISA, and immunoblotting assays. Results: Twenty-eight components were identified in CPEO. CPEO was noncytotoxic to B16BL6 cells at 1–100 μg/mL and reduced serum-induced proliferation in B16BL6 cells. CPEO significantly inhibited α-MSH-stimulated increases in melanin synthesis and tyrosinase activity in the cells (e.g., at 100 μg/mL CPEO, melanin synthesis: 117.89 ± 0.00% vs. 571.94 ± 0.81% with α-MSH; tyrosinase activity: 73.62 ± 0.00% vs. 322.60 ± 3.10% with α-MSH). CPEO also downregulated the expression levels of melanogenesis-related proteins (MITF, tyrosinase, TRP-1 and -2) and melanosome transport-related proteins (Rab27a, melanophilin, myosin Va) in cells exposed to α-MSH. Moreover, the essential oil increased the phosphorylations of MAPKs (p38, ERK1/2, and JNK) in α-MSH-treated B16BL6 cells. In addition, CPEO reduced the ultraviolet A (UVA) induced increases in α-MSH levels in HaCaT cells. In addition, conditioned medium from HaCaT cells irradiated with UVA (CM-UVA) in the presence of CPEO reduced melanin synthesis and tyrosinase activity in B16BL6 cells (e.g., at CM-UVA with 100 μg/mL CPEO, melanin synthesis: 100.92 ± 0.99% vs. 134.44 ± 0.97% with CM-UVA; tyrosinase activity: 101.02 ± 1.81% vs. 133.77 ± 1.88% with CM-UVA). Conclusions: These findings suggest that CPEO inhibits melanin production (probably through the regulation of MAPKs) and transport-related activities in B16BL6 cells, and that CPEO may serve as a potential natural anti-hyperpigmentation or skin whitening.

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  • Open Access Icon
  • Research Article
  • 10.3390/pharmaceutics17111377
Advances in Oral Drug Delivery Systems for Natural Polyunsaturated Fatty Acids: Enhancing Bioavailability and Therapeutic Potential
  • Oct 24, 2025
  • Pharmaceutics
  • Matheus Felipe Zazula + 10 more

Omega-3 and omega-6 fatty acids play essential roles in human health, being widely used in the prevention and treatment of various conditions, such as cardiovascular diseases, inflammation, and metabolic disorders. However, their oral administration faces significant challenges, including low solubility, rapid oxidation, and low bioavailability, which limit their therapeutic efficacy. This article explores recent advances in oral drug delivery systems designed for polyunsaturated fatty acids, highlighting how innovative technologies, such as nanoemulsions, liposomes, microencapsulation, and solid lipid nanoparticles (SLNs/NLCs), can improve their stability, absorption and clinical performance. In addition, the main natural sources of these compounds, as well as their extraction and purification methods, and the challenges related to their absorption and metabolism are discussed. This narrative review was based mainly on a comprehensive search of peer-reviewed literature published between 2015 and 2025 in PubMed, Scopus, and Web of Science. The therapeutic benefits of these emerging approaches are analyzed by comparing conventional methods with modern delivery strategies to optimize the use of omega-3 and omega-6 in the body. Finally, the article outlines future perspectives and regulatory challenges associated with these technologies, highlighting their potential to revolutionize the administration of essential fatty acids and broaden their applications in medicine and nutrition.

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  • Open Access Icon
  • Research Article
  • 10.3390/pharmaceutics17111375
Extended Stability of Ascorbic Acid in Pediatric TPN Admixtures: The Role of Storage Temperature and Emulsion Integrity
  • Oct 24, 2025
  • Pharmaceutics
  • Rafał Chiczewski + 3 more

Background/Objectives: This study assessed the chemical and physical stability of ascorbic acid in pediatric total parenteral nutrition (TPN) admixtures under conditions reflecting both hospital compounding and home administration. Methods: Two storage protocols were examined: (A) refrigerated storage (15 days, 4 ± 2 °C) followed by addition of ascorbic acid and a 24-h period of storage at room temperature, and (B) vitamin supplementation within 24 h after composing and storage at 21 ± 2 °C. A validated high-performance liquid chromatography (HPLC) method was used to quantify ascorbic acid degradation. Physical stability was evaluated via optical microscopy, dynamic light scattering (DLS), laser diffraction (LD), zeta potential, and pH measurement. Results: Ascorbic acid content remained above 90% of the declared value in both protocols, although gradual degradation was observed with increasing storage time and temperature. Emulsion droplet sizes remained within pharmacopeial limits (<500 nm), and no coalescence or phase separation was detected. Zeta potential values (−20 to −40 mV) confirmed kinetic stability, while pH ranged from 5.8 to 6.2, remaining within acceptable safety margins. Conclusions: Vitamin C in pediatric TPN admixtures is stable under refrigerated conditions for up to 15 days. However, the additional 24 h at room temperature resulted in measurable loss of ascorbic acid content, suggesting a need for improved guidance in home-based parenteral nutrition, particularly regarding transport and handling. The study underscores the importance of strict cold-chain maintenance and highlights the role of emulsion matrix and packaging in protecting labile vitamins. This research provides practical implications for hospital pharmacists and caregivers, supporting better formulation practices and patient safety in pediatric home TPN programs.

  • New
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  • Research Article
  • 10.3390/pharmaceutics17111376
Correction: Badea et al. Carboxyl-Functionalized Carbon Nanotubes Loaded with Cisplatin Promote the Inhibition of PI3K/Akt Pathway and Suppress the Migration of Breast Cancer Cells. Pharmaceutics 2022, 14, 469
  • Oct 24, 2025
  • Pharmaceutics
  • Madalina Andreea Badea + 5 more

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  • New
  • Open Access Icon
  • Research Article
  • 10.3390/pharmaceutics17111380
Volatile Compounds as Upcoming Antigiardial Agents: In Vitro Action of Carvacrol, Thymol and p-Cymene on Giardia lamblia Trophozoites
  • Oct 24, 2025
  • Pharmaceutics
  • Marisa Machado + 4 more

Background/Objectives: Carvacrol and thymol are monoterpenes present in phenolic-rich essential oils extracted from aromatic plants that exhibit antimicrobial activity. This study evaluates the antiprotozoal effect of carvacrol, thymol and their precursor, p-Cymene, against Giardia lamblia and investigates their mechanism of action and cytotoxicity profile. Methods: G. lamblia susceptibility, cell viability, swelling and adhesion abilities following application of carvacrol, thymol and p-Cymene were assessed. Ultrastructural changes were evaluated using electron microscopy. Cytotoxicity was determined in mammalian cell lines (murine macrophages RAW 264.7 and bovine aortic endothelial cells) exposed to the same IC50 concentrations effective against G. lamblia. Results: Carvacrol and thymol led to significant inhibition of G. lamblia trophozoite proliferation (IC50 ≅ 50 µg/mL). After 7 h of incubation, total cell number decreased by 30% (p < 0.01) with carvacrol and by 50% (p < 0.001) with thymol, accompanied by reduced motility and adhesion (<20% attached cells). At IC50 concentrations, G. lamblia trophozoites exposed to carvacrol and thymol underwent considerable ultrastructural alterations (e.g., aberrant-shaped cells, mitochondrial swelling and autophagosomal structures). Reduced trophozoite motility and adhesion capacity were also observed. In mammalian cells, thymol showed no significant cytotoxicity, whereas carvacrol significantly reduced viability in both cell lines. In contrast, p-Cymene showed no antigiardial activity. Conclusions: Our data suggests that carvacrol and thymol disrupt G. lamblia trophozoite integrity, possibly through alterations in membrane permeability and osmoregulatory processes. In conclusion, these compounds reveal in vitro antigiardial activity, supporting their potential as antigiardial drugs.

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  • Research Article
  • 10.3390/pharmaceutics17111382
Hydrogel-Based Therapeutic Strategies for Periodontal Tissue Regeneration: Advances, Challenges, and Future Perspectives
  • Oct 24, 2025
  • Pharmaceutics
  • Bowen Wang + 5 more

Periodontitis, a prevalent chronic infectious disease triggered by oral biofilm microbiota, results in progressive destruction of periodontal supporting tissues, and conventional treatments have limited therapeutic effects on it. Hydrogels, due to their excellent biocompatibility, three-dimensional extracellular matrix-like structure, and localized sustained-release properties, can provide support for cell attachment, promote cell proliferation and differentiation, and improve drug utilization efficiency, showing great promise for applications in treating periodontitis as well as promoting periodontal tissue regeneration. This article first introduces the limitations of current periodontitis treatments and the unique advantages of hydrogels in periodontitis treatment and periodontal tissue regeneration, and then provides an overview of the classifications of hydrogels, the active substances they can load, and the characteristics and functions of these active substances. Subsequently, the article introduces the latest advances in the application of several common natural polymer hydrogels in periodontal tissue regeneration. Finally, the article discusses the current limitations of hydrogels in terms of structure and properties, and proposes potential solutions and future development directions in periodontal tissue regeneration.

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  • Research Article
  • 10.3390/pharmaceutics17111381
Photodynamic Therapy with 5-Aminolevulinic Acid Versus Topical Corticosteroids in the Treatment of Oral Lichen Planus: A Randomized Clinical Trial with Lesion Site-Specific Analysis
  • Oct 24, 2025
  • Pharmaceutics
  • Aleksandra Pietruska + 7 more

Objective: Oral lichen planus (OLP) is a chronic immune-mediated condition of the oral mucosa, commonly associated with pain and burning sensations that impair quality of life. This study aimed to compare the efficacy of photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) and topical glucocorticosteroids (CT) in the treatment of OLP, considering lesion location on keratinized and non-keratinized mucosa. Materials and Methods: A randomized clinical trial was conducted on 90 patients with histologically confirmed OLP. Participants were allocated to receive either ALA-PDT in addition to novel oromucosal emulgel containing 5% ALA (five weekly sessions) or clobetasol propionate applied twice daily for two weeks. Lesion area, clinical severity (Reticulation, Erythema, Ulceration—REU index), and subjective symptoms (Visual Analog Scale—VAS) were evaluated before treatment, immediately after, and six months after therapy. Results: ALA-PDT achieved significantly greater and more durable reductions in lesion area, REU scores, and VAS values compared to CT, particularly on non-keratinized mucosa (mean lesion reduction from 2.64 to 0.56 cm2 at six months; p < 0.0001). CT therapy showed initial improvement but was followed by relapse at six months. Both treatments were well tolerated, with only mild transient adverse effects reported. Conclusions: ALA-PDT, especially when applied to non-keratinized oral mucosa, provides superior and longer-lasting therapeutic outcomes than topical CT. The application of novel ALA-loaded emulgel enhances treatment efficacy and tolerability, supporting PDT as a promising alternative for OLP management.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/pharmaceutics17111364
Three-Dimensional Printing in Paediatrics: Innovative Technology for Manufacturing Patient-Centred Drug Delivery Systems
  • Oct 22, 2025
  • Pharmaceutics
  • Nadine Couți + 5 more

Additive manufacturing can be regarded as a game-changing approach for paediatric drug development, as children have special drug-related requirements which are rarely met by conventional technologies. Traditional dosage forms have considerable drawbacks, among them dose, excipient safety, and taste issues, which can be resolved by using three-dimensional (3D) printing. Ease of swallowing and an appealing design are among the improvements brought forth by 3D printing techniques. Techniques that have been thoroughly researched in the paediatric field include hot-melt extrusion (HME) coupled with fused deposition modelling (FDM), direct powder extrusion (DPE) and semisolid extrusion (SSE) 3D printing. Selective Laser Sintering (SLS) 3D bioprinting and binder-jet (BJ) 3D printing are other less known but highly useful techniques. A number of studies focus on significant subjects for the paediatric medicine domain, such as the acceptability of the produced formulations, the size of tablets, the design, the concealment of bitter API flavour, and the stability of the dosage forms. The 3D-printed oral formulations are varied: conventional-sized tablets, miniaturised tablets, chewable tablets, and orodispersible films or tablets. Most of the drugs used in the presented studies are essential medicines for children, for which commercial products with flexible doses and age-appropriate characteristics are often lacking. The practical implications of currently published studies and future directions for paediatric pharmaceutical 3D printing are described. Although there is a substantial amount of technical and in vitro data as well as paediatric engagement work on this subject, its translation into clinical practice is still limited. The clinical efficacy of 3D-printed dosage forms has to be further researched, since only a few studies have targeted this aspect.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/pharmaceutics17111365
Nanoparticle-Based Targeted Drug Delivery Methods for Heart-Specific Distribution in Cardiovascular Therapy
  • Oct 22, 2025
  • Pharmaceutics
  • Toshihiko Tashima

Cardiovascular diseases remain the leading cause of death worldwide and are often managed through invasive surgical procedures such as heart transplantation, ventricular assist device implantation, coronary artery bypass grafting, and stent placement. However, significant unmet medical needs persist in this field. The development of pharmaceutical agents using non-invasive delivery strategies is therefore of critical importance. Current treatments often target peripheral tissues or organs—such as capillary endothelial cells, vascular smooth muscle, and renal tubules—to reduce cardiac workload by lowering blood pressure. However, effective drug delivery directly to the myocardium continues to pose a significant challenge. For conditions such as congestive heart failure (CHF) and myocardial infarction (MI), targeted delivery of therapeutic agents to the heart is essential. In this perspective review, I discuss the potential and emerging strategies for non-invasive cardiac drug delivery, focusing on receptor-mediated endocytosis and transcytosis using nanoparticle-based delivery systems that have frequently been employed for targeting the brain or cancer cells although their use for cardiac delivery remains largely unexplored.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/pharmaceutics17101358
Influence of Selected Hypromellose Functionality-Related Characteristics and Soluble/Insoluble Filler Ratio on Carvedilol Release from Matrix Tablets
  • Oct 21, 2025
  • Pharmaceutics
  • Tadej Ojsteršek + 2 more

Background/Objectives: This study investigated how selected functionality-related characteristics (FRCs) of hypromellose (HPMC)—namely viscosity, hydroxypropoxy substitution, particle size, and the ratio of water-soluble (FlowLac® 100) to water-insoluble (Avicel® PH-102) fillers— affect the release of carvedilol from matrix tablets. Methods: Using a Central Composite Design (CCD) Design of Experiments (DoE), mixtures of HPMC QbD samples were prepared to achieve target HPMC FRC levels. Within the CCD, levels of FlowLac® 100 and Avicel® PH-102 were also varied. The mean and standard deviation of carvedilol release at each analyzed time point of the release profile were used as target variables for individual multiple linear regression (MLR) models. Results: Lactose, the water-soluble filler, significantly accelerated carvedilol release, whereas the water-insoluble MCC slowed and stabilized release by improving gel integrity. Among the HPMC FRCs, particle size had the strongest influence during the early release phase, while HPMC viscosity and hydroxypropoxy substitution degree became more important in later phases. Analysis of the results using optimized multiple linear regression (MLR) models revealed key interaction effects, particularly between HPMC viscosity and lactose content, and between viscosity and particle size, demonstrating their combined role in modulating release kinetics. Conclusions: These findings provide valuable insight into how controlling HPMC’s FRCs and filler composition can reduce interbatch variability in drug release and support the rational design of robust controlled release formulations.