Pharmaceutics最新文献

Background/objectives: Bovine mastitis (BM), a prevalent and economically burdensome bacterial infection affecting dairy cattle, poses a significant challenge to the dairy industry. The traditional approach to combating BM, relying heavily on antibiotics, faces growing concerns due to the increasing antibiotic resistance exhibited by pathogens. The objective of this study was to evaluate and determine the antimicrobial and anti-biofilm potential of chitosan nanoparticles (NQo) on S. aureus strains isolated from milk samples obtained from dairy areas in southern Chile from cows diagnosed with BM.

Methods: NQo were synthesized using the ionotropic gelation method and thoroughly characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS).

Results: The NQo exhibit a robust positive charge (Z-potential of +55.4 ± 2.5 mV) and an exceptionally small size (20.3 ± 3.2 nm). This unique combination of properties makes NQo particularly well-suited for targeting and interacting with bacterial pathogens. To assess the effectiveness of NQo against BM, we conducted a series of experiments using a Staphylococcus aureus strain isolated from milk samples of cows diagnosed with BM in southern Chile. NQo demonstrated a remarkable ability to inhibit bacterial proliferation and effectively modulate biofilm formation in the S. aureus strains. Furthermore, the performance of NQo in comparison to established antibiotics like ampicillin and gentamicin strongly suggests that these nanoparticles hold immense potential as an attractive alternative for the control, prevention, and/or treatment of BM.

Conclusions: NQo exhibit both antimicrobial and antibiofilm activity against a clinically relevant BM pathogen. Further investigations are necessary to develop a hydrogel formulation optimized for effective delivery to the target diseased tissue.

Probiotics provide significant health benefits, but their viability is often compromised during production, storage, and passage through the gastrointestinal tract. These challenges hinder their effective incorporation into functional applications, particularly in dairy functional foods, in which factors such as acidity, oxygen exposure, and storage conditions negatively impact cell survival. The focus was on functional dairy foods, particularly on pasta filata cheeses. Indeed, the use of probiotics in pasta filata cheeses presents significant challenges due to the specific manufacturing processes, which encompass the application of high temperatures and other harsh conditions. These factors can adversely affect the viability and availability of probiotic microorganisms. However, microencapsulation has emerged as a promising solution, offering a protective barrier that enhances probiotic stability, improves survival rates, and facilitates targeted release in the gastrointestinal environment. This review examines the pivotal role of microencapsulation in stabilising probiotics for functional applications, emphasising its relevance in high-value food systems. Functional applications, including foods designed to offer essential nutritional benefits and promote host health, play a crucial role in disease prevention and immune system support, reducing the risk of infections and other physiological impairments. Key microencapsulation technologies are analysed, focusing on their benefits, limitations, and challenges related to scalability and industrial implementation. Additionally, this review discusses strategies to optimise formulations, ensure the sensory quality of final products, and explore future opportunities for expanding innovative applications that align with growing consumer demand for health-promoting solutions.

Background/Objectives: Docetaxel is a potent anti-cancer agent capable of treating various types of cancer. However, it often induces a range of adverse reactions when used with its standard solubilizer, Tween-80, necessitating allergy prophylaxis with dexamethasone prior to administration. To mitigate the risk of allergic reactions, with nanomicelles garnering significant interest due to their enhanced solubility and thermodynamic stability. Methods: In this research, a mPEG-PLA-Lys(Fmoc) micellar carrier with m = 45 and n = 10 was engineered to encapsulate docetaxel, and its self-assembly into micelles was investigated. Additionally, allergic reaction studies were conducted on animals. Results: The findings indicated that the formulation did not cause hemolysis, vascular, or muscle irritation in rabbits, nor did it elicit an allergic response in guinea pigs. Conclusions: These results suggest that nanomicelle-encapsulated docetaxel can diminish the allergic reactions associated with docetaxel injections, offering a novel approach to enhance the therapeutic utility of this outstanding anti-cancer drug.

Background/objectives: Oral mucositis (OM) is a common and debilitating side effect of cancer therapy, characterized by ulceration or inflammation of the oral mucosa. This study evaluates the preclinical efficacy of curcumin-loaded bicosome systems (cur-BS) in mitigating chemotherapy-induced OM in mice.

Methods: BS were prepared using a combination of 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), α-tocopherol, and curcumin, encapsulated within liposomal vesicles. Three formulations with different curcumin concentrations (180, 540, and 900 μM) were characterized by particle size, polydispersity index (PDI), encapsulation efficiency (EE), appearance, and morphology. The formulation with the highest concentration (cur-BS 5×) was selected for ex vivo permeability studies, release profile analysis, and in vitro anti-inflammatory efficacy. OM was induced in mice using 5-fluorouracil (5-FU) and acetic acid. Cur-BS 5× was compared to the commercial product Dentoxol^®.

Results: The results showed that cur-BS 5× provided sustained release through a mechanism involving both diffusion and matrix relaxation, enhancing curcumin retention in deeper skin layers. Treatment with cur-BS 5× downregulated the expression of inflammatory markers (IL-1β and TNF-α). Macroscopic assessments demonstrated that both cur-BS 5× and Dentoxol^® reduced OM severity, with the greatest improvement observed between days 6 and 9. By day 24, OM scores were 1.25 ± 0.5 for cur-BS 5× and 1.0 ± 0.0 for Dentoxol^®, indicating effectiveness in both treatments. However, histological analysis revealed superior tissue recovery with cur-BS 5×, showing better epithelial structure and reduced inflammation. Cur-BS 5×-treated mice also exhibited greater weight recovery and higher survival rates compared to the Dentoxol^® group.

Conclusions: These findings suggest that cur-BS 5× may enhance OM treatment, offering outcomes comparable to or better than those of Dentoxol^®.

Background/Objectives: Interest in 3D printing oral thin films (OTFs) has increased substantially. The challenge of 3D printing is film printability, which is strongly affected by the rheological properties of the ink and having suitable mechanical properties. This research assesses the suitability of sodium starch glycolate (SSG), a swellable cross-linked biopolymer, on ink rheology and the film's mechanical properties. Methods: A water-based ink comprising sodium alginate (SA), the drug fenofibrate (FNB), SSG, glycerin, and polyvinylpyrrolidone (PVP) was formulated, and its rheology was assessed through flow, amplitude sweeps, and thixotropy tests. Films (10 mm × 15 mm × 0.35 mm) were 3D-printed using a 410 µm nozzle, 50% infill density, 60 kPa pressure, and 10 mm/s speed, with mechanical properties (Young's modulus, tensile strength, and elongation at break) analyzed using a TA-XT Plus C texture analyzer. Results: The rheology showed SSG-based ink has suitable properties (shear-thinning behavior, high viscosity, higher modulus, and quick recovery) for 3D printing. SSG enhanced the rheology (viscosity and modulus) of ink but not the mechanical properties of film. XRD and DSC confirmed preserved FNB crystallinity without polymorphic changes. SEM images showed surface morphology and particle distribution across the film. The film demonstrated a drug loading of 44.28% (RSD 5.62%) and a dissolution rate of ~77% within 30 min. Conclusions: SSG improves ink rheology, makes it compatible with 3D printing, and enhances drug dissolution (formulation F-5). Plasticizer glycerin is essential with SSG to achieve the film's required mechanical properties. The study confirms SSG's suitability for 3D printing of OTFs.

Background/Objectives: Numerous diseases such as diabetes, Alzheimer's disease, and cancer have spread in the whole world, especially in the Arab world. Also, various applications of Schiff-base functionalized nanoparticles and copper oxide nanoparticles (CuO-NPs) such as therapeutic applications have been discovered. Thus, the current research highlights (i) the synthesis of copper oxide nanoparticles (CuO-NPs) produced with a Schiff base (SB) serving as a capping agent during their synthesis and (ii) assessment of the in vitro biological activities of Schiff base-synthesized copper oxide nanoparticles (SB-CuO-NPs) and a Schiff base (SB). Methods: SB-CuO-NPs were characterized using ultraviolet-visible (UV-Vis) spectroscopy, zeta potential, DLS analysis, and transmission electron microscope (TEM). It also focuses on assessing the in vitro biological applications and activities, including antioxidant, scavenging, anti-diabetic, anti-Alzheimer, anti-arthritic, anti-inflammatory, cytotoxic activities, and enzymes inhibitory potential, of Schiff base-synthesized copper oxide nanoparticles (SB-CuO-NPs) and a Schiff base (SB) using methods described in the literature. Results: The results of the biological activities of the SB-CuO-NPs were compared with those of the SB. The SB-CuO-NPs demonstrated superior in vitro biological activities when compared to the SB from which they were produced. Conclusions: The results of this investigation concluded that the CuO-NPs, synthesized with the SB serving as an alternative capping agent, exhibited enhanced biological efficacy relative to the original SB. In the future, the biological efficiency of SB-CuO-NPs against diabetes, Alzheimer's, and cancer diseases will be assessed in experimental animals (in vivo).

Background: Colistin, a lipopeptide antibiotic usually used as a last resort against multidrug-resistant bacterial strains, has also begun to address the challenge of antimicrobial resistance. Objective: this study evaluates whether hybrid nanoparticles (HNPs) composed of Phospholipon^® 90G, cholesterol, and colistin can enhance its effectiveness against resistant clinical isolates of Klebsiella pneumoniae, a clinically significant Gram-negative bacterium. Methods: HNPs were developed using the ethanol injection method and coated with chitosan through a layer-by-layer technique. HNP characterization included measurements of particle size, polydispersity index (PDI), and zeta potential, along with thermal (DSC) and spectrophotometric (FT-IR) analyses. Ultrafiltration and ATR-FTIR were employed to assess colistin's association and release efficiencies. The biological evaluation followed CLSI guidelines. Results: uncoated hybrid nanoparticles (U-HNP) and chitosan-coated hybrid nanoparticles (Ch-HNP) described monodisperse populations, with respective PDI values of ~0.124 and ~0.150, Z-averages of ~249 nm and ~250 nm, and zeta potential values of +17 mV and +20 mV. Colistin's association and release efficiencies were approximately 79% and 10%, respectively. Regarding antimicrobial activity, results showed that colistin as part of HNPs is poorly effective against this microorganism. However, in the most resistant strain, colistin activity increased slightly when the HNP was coated with chitosan. Conclusions: HNPs described high stability against disaggregation, limiting the colistin release and, therefore, affecting antimicrobial performance.

Lipid nanoparticles (LNPs) are versatile delivery systems with high interest because they allow the release of hydrophobic and hydrophilic molecules, such as essential oils (EOs) and plant extracts. This review covers published works between 2019 and 2024 that have reported the use of essential EO-based LNPs with antimicrobial properties and applications in human and animal health, as well as biopesticides. In the human healthcare field, reports have addressed the effect of encapsulating EOs in lipid nanosystems with antiviral, antibacterial, antiprotozoal and antifungal activities. In animal care, this still needs to be more deeply explored while looking for more sustainable alternatives against different types of parasites that affect animal health. Overall, the antibacterial activities of LNPs carrying EOs are described as alternatives to the use of synthetic antibiotics. In the field of agriculture, studies showed that these approaches in the control of phytopathogens and other pests that affect food production. There is a growing demand for innovative and more sustainable technologies. However, there are still some challenges to be overcome in order to allow these innovations to reach the market.

Background/Objectives: Venlafaxine (VEN) is commonly used in young and elderly patients. Bupropion (BUP) is occasionally added to depression treatments with VEN. BUP's inhibitory potential toward CYP2D6, VEN's main metabolic pathway, may provoke a higher risk for toxic or adverse drug effects. Therefore, the question arises if a dose reduction in VEN or BUP is needed to avoid clinically relevant changes in exposure to VEN and its metabolite O-desmethylvenlafaxine (ODV). Methods: The literature-based PBPK models of VEN, BUP and their active metabolites under single-dose and steady-state conditions were created by using PK-Sim^®. To evaluate the DDI model's predictive performance, trough plasma concentrations (<65 years, n = 54 and ≥65 years, n = 13) of VEN/ODV were extracted from the TDM database KONBEST. DDI's clinical extent was assessed by AUC changes in VEN, ODV and active moiety (AM). The prediction was compared to the results of SCHOLZ Databank's MDDI calculator (MDDIcalc). Results: Models accurately describe VEN's and BUP's pharmacokinetics and BUP's effect on VEN's metabolism in the age strata. The model predicts higher exposure to VEN (+110% to 132%), lower exposure to ODV (-50.0% to -61.5%) and a negligible change in AM (-1.02% to -2.40%). The AUC changes increase with higher BUP doses but is independent of patients' age. Because of the missing AUC change in the AM, the DDI is considered clinically irrelevant. The MDDIcalc predicts no relevant effect on the AUC of AM with BUP. Conclusions: Both PBPK and MDDIcalc provide, in their own way, valuable tools to predict the DDI's extent. Further research is needed regarding elderly patients, renal or hepatic impairment and polymorphisms, especially CYP2D6, CYP2C9, CYP2C19 and UGT.

Background: The excessive accumulation of Aβ plays a critical role in the development of Alzheimer's disease. However, the therapeutic potential of drugs like curcumin is often limited by low biocompatibility and BBB permeability. In this study, we developed a nanomaterial, BP-PEG-Tar@Cur, which was designed to enhance the biocompatibility of (curcumin) Cur, target Aβ, and augment BBB permeability through near-infrared (NIR) photothermal effects. Methods: Soluble Aβ, ThT fluorescence, and Aβ depolymerization fluorescence experiments were conducted to evaluate the ability of BP-PEG-Tar@Cur to inhibit Aβ aggregation and dissociate Aβ fibrils. Cell uptake assays were performed to confirm the targeting ability of BP-PEG-Tar@Cur towards Aβ. In vitro mitochondrial ROS clearance and in vivo detection of inflammatory factors were used to assess the anti-inflammatory and antioxidant properties of the nanodrug. Water maze behavioral experiments were conducted to evaluate the effect of BP-PEG-Tar@Cur on spatial memory, learning ability, and behavioral disorders in AD mice. Results: The nanodrug effectively inhibited Aβ aggregation and dissociated Aβ fibrils in vitro. BP-PEG-Tar@Cur demonstrated efficiency in curbing ROS overproduction in mitochondria and dampening the activation of microglia and astrocytes triggered by Aβ aggregation. Water maze behavioral experiments revealed that BP-PEG-Tar@Cur enhanced spatial memory, learning ability, and alleviated behavioral disorders in AD mice. Conclusions: Collectively, these findings demonstrate that BP-PEG-Tar@Cur has the potential to be an effective targeted drug for inhibiting Aβ aggregation and improving cognitive impairment in AD mice.