Search Results (6,714)

The antibacterial properties of Ag(I) coordination compounds are well documented; however, their effectiveness is highly dependent on the choice of appropriate ligands, and it is frequently hindered by their low water solubility and limited bioavailability. Herein, six new Ag(I) complexes incorporating the quinazolinone thioamide mqztH (=2-mercapto-4(3H)-quinazolinone) and phosphine co-ligands were synthesized and investigated for their antibacterial activity. In vitro activity assays against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial strains revealed that all complexes selectively inhibited S. aureus bacterial growth. Structure–activity relationship analysis showed that monodentate PPh₃ co-ligands play a key role in enhancing the antibacterial efficacy of their complexes. Notably, complex [AgCl(mqztH)(PPh₃)₂] (1) exhibited broad-spectrum activity, with IC₅₀ values of 4.2 ± 1.4 μg mL^–1 (4.9 μΜ) for S. aureus and 63 ± 1.9 μg mL^–1 (75 μΜ) for E. coli bacteria. To improve solubility and antibacterial activity, complex 1 was encapsulated in barium alginate (BaAlg) matrices to form hydrogel-based drug delivery formulations [¹]@BaAlg. The synthesized formulations retained the bactericidal effect of the complex, achieving comparable activity at concentrations lower by an order of magnitude compared to complex 1 in free form. Combined with the demonstrated high biocompatibility of complex 1 toward L929 normal eukaryotic cells, as well as the biocompatible nature of the alginate matrix, these findings underscore the strong potential of the complex 1-loaded hydrogel formulations for further investigation and development as effective antibacterial drug platforms. Mechanistic studies confirmed the redox-active nature of complex 1 and its potential to inhibit the function of glutathione reductase (GR) and thioredoxin reductase (TrxR) at low concentrations, suggesting the interference with bacterial redox homeostasis as a relevant mechanism of bioactivity. Full article

Resveratrol (RES), a naturally occurring polyphenolic compound with well-documented anticancer potential, is limited in clinical application due to its poor aqueous solubility and low bioavailability. This study aimed to develop RES-loaded liposomes coated sequentially with chitosan (CS) and hyaluronic acid-chitosan (HA) (RES-HA-CS-Lip) to enhance RES stability, delivery, and anticancer efficacy in breast cancer cells. HA-CS-coated liposomes were prepared using a thin-film hydration technique. Their physicochemical characteristics were thoroughly investigated through dynamic light scattering, transmission electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The optimized RES-HA-CS-Lip exhibited spherical morphology with an average particle size of 212 nm, a narrow polydispersity index (<0.4), a zeta potential of +9.04 ± 1.0 mV, and high entrapment efficiency of 82.16%. Stability studies demonstrated superior retention of size, surface charge, and encapsulation efficiency over 28 days at both 4 °C and 25 °C. In vitro release profiles at physiological and acidic pH revealed sustained drug release, with enhanced release under acidic conditions mimicking the tumor microenvironment. Antioxidant activity, assessed via DPPH and ABTS radical-scavenging assays, indicated that RES retained its radical-scavenging potential upon encapsulation. Cytotoxicity assays demonstrated markedly improved anticancer activity against MCF-7 breast cancer cells, with an IC₅₀ of 13.08 μg/mL at 48 h, while maintaining high biocompatibility toward normal HaCaT keratinocytes. RES-HA-CS-Lip demonstrated excellent stability against degradation and aggregation. Overall, these findings highlight HA-CS-coated liposomes as a promising polysaccharide-based nanocarrier that enhances stability, bioactivity, and therapeutic efficacy of RES, representing a potential strategy for targeted breast cancer therapy. Full article

Background: Amlodipine besylate (AML) is recognized as a calcium channel blocker curative for hypertension. However, the drug emerged recently as an antibacterial cure that competently prevails over resistant strains. Methods: Incorporating amlodipine into zein nanoparticles was employed to innovate a suitable carrier for loading and targeting deep corneal infection. The Box–Behnken design was adopted to produce various formulations of amlodipine-loaded zein nanoparticles (AML-ZNs) with diversity in composition concentration (% w/v), comprising zein, Labrafac, and poloxamer 407. Results: Relying on the optimization criterion, the chosen preference formulation concentration (% w/v) consists of 2.068 for zein, 0.75 for Labrafac, and 1.0 for Poloxamer. Morphological micrography of AML-ZNs showed regular spherical particles in the nanometric scale, and physicochemical characterization procedures confirmed system suitability. While tracking eyedrop optimum features, sodium alginate was selected for coating nanoparticles to improve stability and system viscosity. Both pH and sterility were also considered and maintained. Comparative studies were conducted pre- and post-coating, and the assessed features for the final selected formulation were 349.9 ± 5.8 nm, 0.2186 ± 0.0271, −55.45 ± 1.84 mV, 81.293 ± 0.9%, and 19.3 ± 0.19 cp for size, PDI, surface charge, entrapment, and viscosity, respectively. The AML-ZNs-Alg formulation demonstrates a more controlled pattern of release of roughly 40% of the drug released after 48 h, while the permeation profile shows 37 ± 3.52% permeated after 24 h, confirmed visually. In vitro microbial assay alongside the corneal in vivo microbial and histological pathology evaluation proved the efficacy of amlodipine as an antibacterial agent. Conclusions: These findings highlighted that the prepared AML-ZNs-Alg eyedrop can be a promising system as an antibacterial therapy. Full article

Oral administration remains the most patient-friendly drug delivery route, yet its efficacy is limited by physiological barriers including gastric degradation and inefficient cellular uptake. pH-responsive nanogels have shown promise for gastrointestinal drug delivery, though their effectiveness is often constrained by poor membrane interaction. Inspired by natural membrane-anchoring mechanisms, a series of comb-like anionic polymers were designed via grafting alkylamines of different chain lengths (C₁₀, C₁₄, C₁₈) at varying densities (10–30%) onto a biodegradable poly(L-lysine isophthalamide) (PLP) backbone. These pH-responsive comb-like polymers self-assembled into nanogels for loading the hydrophobic chemotherapeutic agent camptothecin. The alkyl length and grafting density significantly influenced pH-responsive behavior, membrane disruption, and drug release profiles. The optimal formulation—the nanogel prepared with PLP grafted 30% C₁₄—achieved a high drug-loading capacity, ideal particle size and stability, and offered superior protection in acidic conditions (only 7 ± 5% release at pH 1.2 over 24 h), while enabling rapid intestinal release (78 ± 2% at pH 7.4 within 24 h). The nanogels significantly enhanced cellular uptake, cytoplasmic delivery, and cytotoxicity against colorectal carcinoma cells. This study demonstrates the key role of hydrophobic modification in designing effective oral nanocarriers, providing a promising platform for the treatment of intestinal diseases. Full article

Background: Despite considerable advances to improve colorectal cancer (CRC) survival over the last decade, therapeutic challenges remain due to the rapid metastatic dissemination of primary tumors. This study revealed the apoptotic and anti-growth mechanism of VTD, a previously used anti-hypertensive supplement, can elevate UBXN2A, a known tumor suppressor protein in CRC, and simultaneously enhance intrinsic and extrinsic apoptosis in metastatic cancer cells. Methods and Results: An AOM/DSS mouse model of CRC showed that UBXN2A haplosufficient (UBXN2A +/−) mice treated with VTD had less tumor burden than mice with the full UBXN2A gene treated with vehicle. We have previously shown that casein-coated mesoporous silica nanoparticles (MSNs) offer an effective local delivery of drugs at tumor sites. Our findings demonstrate that the high rate of extracellular release of matrix metalloproteinases (MMPs), particularly MMP-7, by metastatic colon cancer cells, triggers the release of VTD from casein-coated mesoporous MSNs. This shows the “Zip Code” mechanism for the local enrichment of VTD at the tumor sites. After in vitro drug release verification, two independent mouse experiments, a xenograft and a splenolepatic metastatic mouse model of CRC, were used to evaluate the therapeutic efficacy of VTD-loaded and casein-coated carboxylated mesoporous silica nanoparticles, MSN-COOH/VTD/CAS (VTD, 0.2 mg/kg). Animal experiments revealed that MSN-COOH/VTD/CAS (VTD, 0.2 mg/kg) slows down the progress of tumors. Mass spectrometry (MS) revealed improved pharmacokinetics (PK) profile as MSN-COOH/VTD/CAS had less VTD accumulation in non-cancerous organs compared to pure VTD. We further improved nanoparticle targeting and drug release by shifting to calcium-based particles (CBPs). The engineered CBPs demonstrated higher drug-releasing performance. Without the MMPs trigger, MSNs show slow and continuous “drug leak” over longer period of time whereas CCSMPs stops leakage within an hour. Additionally, CBPs showed higher sensitivity to MMP-7 than MMP-9, enhancing the targetability of CBPs for CRC metastatic tumors with excessive extracellular MMP-7. Conclusions: This study introduces a new platform utilizing nanoparticle-based site-specific delivery of a plant-based anti-metastatic molecule, veratridine, with enhanced safety and therapeutic efficacy for the treatment of metastatic CRC. Full article

Background/Objectives: The present work deals with the sol–gel synthesis of hybrid materials based on a silica–polyvinylpyrrolidone (Si-PVP) system. Methods: The nanohybrids have been prepared using an acidic catalyst at ambient temperature. Ibuprofen (IBP) was used as a model substance in the obtained model drug systems, while tetraethyl orthosilicate (TEOS) was used as a silica precursor. Poly(vinylpyrrolidone) (PVP) and IBP were introduced into the reaction mixture as solutions in ethanol using two different approaches: (i) a direct introduction of a drug solution into the reaction mixture during sol–gel synthesis, and (ii) a solvent deposition technique. Results: XRD data provide evidence that IBP entrapped in the silica–PVP network is in an amorphous state. By SEM it was revealed that in the adsorbate, the IBP particles possess an average particle size of about 20 μm. Based on the obtained IR and UV-Vis spectral results, the existence of hydrogen bonding of IBF with silica and PVP could be suggested. Solid-state NMR analysis allowed the identification of the presence of both crystalline-like and amorphous phases in the hybrid material prepared by the sol–gel method, while it was demonstrated that in the adsorbate, the rigid crystalline dimeric structure of the drug has been preserved. Conclusions: The overall analysis of the structural characteristics of the two materials indicated that in the hybrid material obtained by the sol–gel method, the interactions between the amorphous drug, PVP, and the silica matrix are more pronounced as compared to the adsorbate. An improvement of the drug’s aqueous solubility as well of in vitro drug release profile (up to 8 h) was achieved, demonstrating the potential of the developed drug–silica–organic polymer nanohybrid as a promising drug delivery system. Full article

Background/Objectives: Semi-solid extrusion (SSE) three-dimensional (3D) printing offers a versatile approach for fabricating personalized oral dosage forms. This study aimed to develop and optimize losartan potassium tablets produced via SSE 3D printing, focusing on the effects of polymer composition, tablet geometry, drug loading, and superdisintegrant concentration on printability and performance characteristics. Methods: Formulations containing hydroxypropyl methylcellulose (HPMC) 4500 at various concentrations were evaluated for suitability in an ethanol–water (9:1 v/v) solvent system. The optimized formulation (5% w/w HPMC 4500) was used to print tablets with varying shapes, drug loadings (5–15% w/w; approximately 50–150 mg losartan potassium per tablet), and croscarmellose sodium concentrations (0–3% w/w). Printed tablets were characterized for dimensional accuracy, mass uniformity, disintegration time, and drug release behavior. Drug release kinetics were modeled to elucidate the release mechanism. Results: All SSE-printed tablets exhibited excellent dimensional precision (SD < 0.8 mm) and mass uniformity (SD < 0.12 g). Increasing drug loading enhanced the initial release rate, reaching up to 63% in 45 min for 15% loading. The addition of 1% croscarmellose sodium reduced disintegration time to approximately 25 min. Drug release profiles were best described by the Korsmeyer–Peppas model (R² > 0.96), indicating diffusion-controlled release. Conclusions: SSE 3D printing demonstrated robustness and flexibility in producing losartan potassium tablets with consistent quality, tunable release properties, and strong potential for personalized pharmaceutical manufacturing. Full article

Oleosomes are submicron oil bodies of a triacylglycerol core enveloped by a phospholipid monolayer and embedded proteins, forming a naturally assembled nanocarrier with exceptional oxidative resilience, interfacial stability, and biocompatibility. Their unique architecture supports solvent-free extraction, self-emulsification, and near-complete encapsulation of highly lipophilic compounds (log P > 4), including curcumin and cannabidiol, with reported efficiencies exceeding 95%. These plant-derived droplets enhance oral bioavailability through lymphatic uptake and enable targeted delivery strategies such as magnetically guided chemotherapy, which has reduced tumor burden by approximately 70% in vivo. The review critically examines recent advances in oleosome research, spanning botanical sourcing, green extraction technologies, interfacial engineering, xenobiotic encapsulation, pharmacokinetics, and therapeutic applications across oncology, dermatology, metabolic disease, and regenerative medicine. Comparative analyses demonstrate that oleosomes rival or surpass synthetic lipid nanocarriers in encapsulation efficiency, oxidative stability, and cost efficiency while offering a sustainable, clean-label alternative. Remaining challenges, including low loading of hydrophilic drugs, allergenicity, and regulatory standardization, are addressed through emerging strategies such as hybrid oleosome–liposome systems, recombinant oleosin engineering, and stimulus-responsive coatings. These advances position oleosomes as a versatile and scalable platform with significant potential for food, cosmetic, and pharmaceutical applications. Full article

Background/Objective: The high-shear granulator is considered an effective piece of equipment for layering pelletization because it enhances drug amorphization and improves drug dissolution. This study aimed to apply a high-shear granulator to prepare layered pellets containing a combination of hydrochlorothiazide and amlodipine besylate with improved physicochemical properties. Methods: Different molar ratios (2:1, 1:1, and 1:2) of the hydrochlorothiazide and amlodipine besylate mixture were deposited on the surface of the inert spheres of the microcrystalline cellulose (MCC) core by the mechanical effect of the high impeller speed. The resulting layered pellets were characterized using X-ray powder diffractometry (XRPD) and differential scanning calorimetry (DSC) to estimate the degree of the drug amorphization, and consequently a dissolution test was performed to determine the degree of the enhancement of the percentage of release. Additionally, micro-computed tomography (micro-CT) and a texture analyzer were used to determine the morphological characteristics and hardness of the resulting pellets, and then a stability study was performed. Results: On the basis of the micro-CT images, the MCC core was successfully loaded with a uniform layer of the drug combination at the pellet surface, which exhibited higher diameters than pure cellets. Furthermore, the drug combination in layered pellets was partially amorphized with a lower crystallinity percentage, a lower intensity, a broadening of the hydrochlorothiazide melting peak, and a higher cumulative release of both drugs with good stability, except pellets with a molar ratio of 1:2 that were recrystallized with a higher crystallinity percentage of 79.9%. Conclusions: Modifying the physical form and dissolution behavior of the hydrochlorothiazide and amlodipine besylate combination was achieved by single-step layering pelletization. Full article

Background: Using natural substances for cancer therapy has attracted considerable interest due to their safety and reduced systemic toxicity. Nigella sativa (NS) oil, a traditional natural oil rich in bioactive compounds, possesses significant therapeutic potential. Brucine (BR), an alkaloid, exhibits potent cytotoxicity against various cancer cell lines; however, its poor selectivity and high systemic toxicity limit its clinical application. Objective: To overcome these challenges, this study aimed to enhance drug delivery and improve therapeutic efficacy. Method: A PEGylated nanoemulsion (NE) incorporating NS and BR was developed and characterized for particle size, size distribution, zeta potential, viscosity, and drug content. The in vitro release of BR was evaluated both with and without serum incubation. A quantitative amount of serum protein associated with the surface of the NE was estimated, and a hemolytic safety assay was carried out. Finally, an in vitro cytotoxicity study was conducted, and the in vivo anti-tumor effect of the developed PEGylated BR-loaded NE was evaluated and compared with its naked counterpart. Result: The developed PEGylated BR-loaded NE possessed favorable characteristics as a nanocarrier for parenteral administration, with a particle size of 188.5 nm, a zeta potential of −1.61, a viscosity of 3.4 cP, and 99% drug content uniformity. It released up to 60.4% of BR over 12 h, while only 18.4 µg/µmol of the total lipids were adsorbed on the surface of the formulation, compared with 54.5 µg/µmol for the naked counterpart. The PEGylated NE was safe, inducing less than 5% of hemolysis, and displayed substantial inhibition of MDA cell growth. Conclusions: The PEGylated NE achieved a significant reduction in tumor volume, suggesting that PEGylated NE may serve as a promising platform for enhancing anti-tumor activity. Full article

Background/Objectives: Antibiotic resistance is a major public health concern, with considerable socio-economic consequences. Researchers are exploring alternative strategies, including nanotechnology, which has shown significance in targeted drug delivery. This study evaluates the synergistic antibacterial activity of azithromycin-loaded chitosan nanoparticles (AZM-CSNPs) against azithromycin-resistant clinical respiratory isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae (K. pneumoniae). Methods: A total of 87 sputum samples (n = 87) were collected and analyzed. The ermB gene for K. pneumoniae and the ermA gene for MRSA were used to confirm resistant isolates. Among 87 samples, 29 manifested K. pneumoniae, and 32 exhibited MRSA-positive cultures, confirmed through phenotypic and genotypic methods. The RT-PCR is performed by using a cDNA Kit to determine the gene expression. Results: The results elucidate resistance of K. pneumoniae against several antibiotics, including azithromycin (15 µg), chloramphenicol (30 µg), and amoxicillin (30 µg), while MRSA also showed resistance to cefoxitin (30 µg), azithromycin (15 µg), and gentamycin (10 µg). Reduction in the MIC value of the nanoparticle formulation showed their effectiveness. The AZM-CSNPs combined with cetirizine dihydrochloride helped to down-regulate the resistant genes. Conclusions: Notably, a strong synergistic effect was observed with AZM-CSNPs in combination with cetirizine, significantly enhancing antibacterial efficacy against resistant isolates. Full article

Iron oxide nanoparticles (IONs) exhibit biocompatibility, ease of drug loading, and potential for generating forces and heat in a magnetic field, enhancing Magnetic Resonance Imaging (MRI). This study proposes coating IONs on electrode surfaces to improve performance and neuron bonding. Methods included synthesizing IONs, grafting chondroitin sulfate (CS), and co-depositing with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). Results showed reduced impedance, increased charge storage, and improved signal quality in vivo. Full article

This study focuses on the preparation of poly(HCQM-co-VP) copolymeric nanoparticles (NPs) to enhance the aqueous solubility and bioavailability of the hydrophobic and antitumor molecules HCQ (hydroxychloroquine) and α-TOS (α-tocopheryl succinate). HCQ is covalently incorporated into the polymer backbone, while α-TOS is encapsulated within the nanoparticles by non-covalent interactions. Poly(HCQM-co-VP) was synthesized from a vinyl derivative of HCQ (HCQM) and N-vinylpyrrolidone (VP), with a molar composition of 17% HCQM and 83% VP, providing the optimal hydrophobic/hydrophilic balance for forming, via nanoprecipitation, empty nanoparticles (NPs) with a diameter of 123.6 nm and a zeta potential of −5.8 mV. These nanoparticles effectively encapsulated α-TOS within their hydrophobic core, achieving an encapsulation efficiency (%EE) of 78%. These α-TOS-loaded NPs resulted in smaller diameters and more negative zeta potentials (71 nm, −19.2 mV) compared to the non-loaded NPs. The cytotoxicity of these NPs was evaluated using the AlamarBlue assay on MCF-7 breast cancer cells. The empty NPs showed no toxic effects within the tested concentration range, after 72 h of treatment. In contrast, the α-TOS-loaded NPs, exhibited a pronounced cytotoxic effect on MCF-7 cells with an IC₅₀ value of 100.2 μg·mL⁻¹, thereby demonstrating their potential as controlled drug delivery systems for cancer treatment. These findings contribute to the development of a new HCQ-based polymeric nanocarrier for α-TOS or other hydrophobic drugs for the treatment of cancer and other diseases treatable with these drugs. Full article

Cancer has remained a major global health challenge, with around 20 million new cases and 9.7 million fatalities recorded each year. Even though there has been recent progress in therapies such as radiotherapy, chemotherapy, immunotherapy, and gene therapy, cancer remains a major treatment challenge due to late diagnosis and difficulties in therapeutic effectiveness. Flavonoids, a substantial category of naturally occurring polyphenols, have received considerable interest in recent years for their potential involvement in cancer management and prevention, especially concerning breast cancer. These bioactive compounds, abundant in vegetables, fruits, and herbs, exhibit various therapeutic actions, including antioxidant, anti-inflammatory, and antimutagenic effects. The advanced therapeutic potential of flavonoids, when combined with FDA-approved medicines, offers synergistic effects and enhanced clinical results. Additionally, flavonoid-loaded nano-formulations, involving co-delivery systems, are being explored to increase solubility, stability, and bioavailability, enabling targeted delivery to cancer cells while reducing off-target adverse effects. This review examines the role of flavonoids in the prevention and management of breast cancer, focusing on their dietary sources, metabolism, and pharmacokinetic properties. Furthermore, we explore novel strategies, such as combination therapies with FDA-approved drugs and the application of flavonoid-based nanoformulations, which have the potential to enhance therapeutic outcomes. The clinical application of these strategies has the potential to improve breast cancer treatment and create new opportunities for the advancement of flavonoid-based therapies. Full article

Background: Hepatocellular carcinoma is associated with high mortality and increasing incidence. Sorafenib, a cornerstone of therapy for advanced hepatocellular carcinoma, presents certain disadvantages, including low bioavailability and poor water solubility. This work describes a new strategy for sorafenib-targeted delivery aimed at improving treatment efficiency and reducing side effects. Methods: Magnetic nanoparticles coated with azelaic acid were modified with aptamer molecules that specifically recognize human liver cancer cell line HepG2, ensuring specificity for the tumor tissue. The nanoparticles were further loaded with sorafenib. The obtained drug delivery system was extensively characterized using UV-Vis spectrophotometry, transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. Results: The drug delivery system demonstrated a higher release of sorafenib at acidic pH compared to pH 7.4. The cell internalization of the bare and aptamer-modified magnetic nanoparticles was assessed in HepG2 and human normal foreskin fibroblasts BJ cell lines, demonstrating that the aptamer significantly enhances internalization in tumor cells, while having no impact on healthy cells. Conclusions: The sorafenib-modified nanoparticles exhibited excellent cytocompatibility with BJ cells across all tested concentrations, while showing cytotoxicity towards HepG2 cells at higher concentrations, confirming the selectivity of the system. Full article