International Journal of Pharmaceutics: X最新文献

As performance of ternary amorphous solid dispersions (ASDs) depends on the solid-state characteristics and polymer mixing, a comprehensive understanding of synergistic interactions between the polymers in regard of dissolution enhancement of poorly soluble drugs and subsequent supersaturation stabilization is necessary. By choosing hot-melt extrusion (HME) and vacuum compression molding (VCM) as preparation techniques, we manipulated the phase behavior of ternary efavirenz (EFV) ASDs, comprising of either hydroxypropyl cellulose (HPC)-SSL or HPC-UL in combination with Eudragit® L 100–55 (EL 100–55) (50:50 polymer ratio), leading to single-phased (HME) and heterogeneous ASDs (VCM). Due to higher kinetic solid-state solubility of EFV in HPC polymers compared to EL 100–55, we visualized higher drug distribution into HPC-rich phases of the phase-separated ternary VCM ASDs via confocal Raman microscopy. Additionally, we observed differences in the extent of phase-separation in dependence on the selected HPC grade. As HPC-UL exhibited decisive lower melt viscosity than HPC-SSL, formation of partially miscible phases between HPC-UL and EL 100–55 was facilitated. Consequently, as homogeneously mixed polymer phases were required for optimal extent of solubility improvement, the manufacturing-dependent differences in dissolution performances were smaller using HPC-UL, instead of HPC-SSL, i.e. using HPC-UL was less demanding on shear stress provided by the process.

Synchrotron radiation offers a host of advanced properties, surpassing conventional laboratory sources with its high brightness, tunable phonon energy, photon beam coherence for advanced X-ray imaging, and a structured time profile, ideal for capturing dynamic atomic and molecular processes. However, these benefits come at the cost of operational complexity and expenses. Three decades ago, synchrotron radiation facilities, while technically open to all scientists, primarily served a limited community. Despite substantial accessibility improvements over the past two decades, synchrotron measurements still do not qualify as routine analyses. The intrinsic complexity of synchrotron science means experiments are pursued only when no alternatives suffice. In recent years, strides have been made in technology transfer offices, intermediate synchrotron-based analytical service companies, and the development of high-throughput synchrotron systems at various facilities, reshaping the perception of synchrotron science. This article investigates the practical application of synchrotron X-Ray Powder Diffraction (s-XRPD) techniques in pharmaceutical analysis. By utilizing concrete examples, we demonstrate how high-throughput systems have the potential to revolutionize s-XRPD applications in the pharmaceutical industry, rapidly generating XRPD patterns of comparable or superior quality to those obtained in state-of-the-art laboratory XRPD, all in less than 5 s. Additional cases featuring well-established pharmaceutical active ingredients (API) and excipients substantiate the concept of high throughput in pharmaceuticals, affirming data quality through structural refinements aligned with literature-derived unit cell parameters. Synchrotron data need not always be state-of-the-art to compete with lab-XRPD data. The key lies in ensuring user-friendliness, reproducibility, accessibility, cost-effectiveness, and the streamlined efforts associated with synchrotron instrumentation to remain highly competitive with their laboratory counterparts.

This study aimed to evaluate and better understand the potential impact that a layer of surrounding hydrogel (mimicking living tissue) can have on the drug release from PLGA microparticles. Ibuprofen-loaded microparticles were prepared with an emulsion solvent extraction/evaporation method. The drug loading was about 48%. The surface of the microparticles appeared initially smooth and non-porous. In contrast, the internal microstructure of the particles exhibited a continuous network of tiny pores. Ibuprofen release from single microparticles was measured into agarose gels and well-agitated phosphate buffer pH 7.4. Optical microscopy, scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and X-ray μCT imaging were used to characterize the microparticles before and after exposure to the release media. Importantly, ibuprofen release was much slower in the presence of a surrounding agarose gel, e.g., the complete release took two weeks vs. a few days in well agitated phosphate buffer. This can probably be attributed to the fact that the hydrogel sterically hinders substantial system swelling and, thus, slows down the related increase in drug mobility. In addition, in this particular case, the convective flow in agitated bulk fluid likely damages the thin PLGA layer at the microparticles' surface, giving the outer aqueous phase more rapid access to the inner continuous pore network: Upon contact with water, the drug dissolves and rapidly diffuses out through a continuous network of water-filled channels. Without direct surface access, most of the drug “has to wait” for the onset of substantial system swelling to be released.

Enterococcus faecalis plays the key role in endodontic infections and is responsible for the formation of biofilm on dentin, which causes a resistance against periradicular lesions treatment, consequently the aim of this study is to use nanoparticles entrapping anibacterial agents coated with chitosan that in authors previous study showed a successful in vitro biofilm inhibition, additionally incorporated in thermoresponsive gel.to benefit nanoparticles` small size, and the positive charge of their surfaces that binds with the negatively charged surface of bacterial cell causing its destruction, in addition to the sustained release pattern of the drug based nanoparticles in gel. Therefore, Ciprofloxacin hydrochloride (CIP) encapsulated in PLGA nanoparticles coated with chitosan (CIP-CS-PLGA-NPs), in addition to free CIP, were incorporated in Pluronic® 407/188 to form thermosensitive gels (F1) and (F2), respectively. The thermosensitive gels were tested with regards to rheology, gelling temperature and the release pattern of the drug. A clinical study of the efficacy of F1 and F2 as antibacterial treatments was conducted on patients followed by a comparative studies against CIP and Ca(OH)₂ pastes in terms of biofilm inhibition assay and total bacterial reduction count and percent.The results revealed that F1 and F2 exhibited gelation temperature of 36.9 ± 0.3 °C and 36.0 ± 0.4 °C, viscosity was 15,000 ± 360.6 and 7023.3 ± 296.8 cP respectively. The cumulative release of F1 and F2 after 72 h was 50.03% ± 0.7345 and 77.98% ± 3.122 respectively. F1 was the most efficient treatment against recurrent E.faecalis infection in endodontics that was evident by the highest total bacterial reduction count and percent and biofilm inhibition percent that were recorded in the group treated with F1followed by the group treated with F2. Nanocarriers succeeded in carrying the drug deeply in the root canal and sustaining its effect to abolish the obstinate E. faecalis recurrent infection and its biofilm formation.

Synergistic chemotherapy and photothermal therapy (PTT) holds the promise of addressing the weakness of individualized chemotherapy and PTT. In this study, we synthesized a chemotherapeutic agent, PDA-Ce-CDs, which combines the photothermal conversion ability and the generation of hydroxyl radicals (•OH), enabling synergistic enhancement of antitumor effects. Furthermore, the localized heating effect of NIR radiation promoted the uptake of the PDA-Ce-CDs and enhances the sensitivity of intracellular reactive oxygen species (ROS). Finally, the antitumor activity of the PDA-Ce-CDs was evaluated through cell experiments and tumor-bearing mice experiments, confirming its excellent antitumor efficacy in vivo and in vitro. Our work presents a new strategy in cancer treatment by utilizing carbon dots in combination with photothermal agents for synergistic chemotherapy-photothermal therapy. This innovative approach offers a new therapeutic avenue for synergistic tumor treatment by harnessing the combined effects of photothermal therapy and chemotherapy.

Melatonin (MLT) exhibits antioxidant, ultraviolet protection, anti-inflammatory, and anti-aging properties. However, its effectiveness is limited by instability, a short half-life, and incompatible absorption. In this research, we encapsulated melatonin (MLT) in transfersomes (MT) and niosomes (MN) to enhance their properties and investigate their effects through in vitro cell assays using murine macrophages cells and human foreskin fibroblasts cells. The vesicle morphology, vesicle size, polydispersity index, zeta potential, entrapment efficiency (EE%), attenuated total reflectance-Fourier transform spectroscopy (ATR-FTIR) spectra, along with in vitro release, permeation profiles, and stability study were also evaluated. The results showed that both encapsulations displayed spherical morphology at the nanometric scale, their great physical stability and provided an EE% range of 58–78%. The MLT incorporation into the vesicle was confirmed by the ATR-FTIR spectra. Additionally, the encapsulation’ release profiles fitted with the Higuchi model, indicating controlled release of melatonin. Furthermore, MT showed greater permeability than MN and MS including melatonin deposition. In cell assays, MT exhibited significantly higher nitric oxide inhibition and stimulation of collagen compared to MN and MS. Therefore, MT demonstrated the highest possibility for anti-inflammatory and collagen-stimulating activities that could be applied in pharmaceutical or anti-aging cosmetic products.

Combination therapy represents a promising strategy in cancer management by reducing chemotherapy resistance and associated side effects. Silymarin (SLM) has been extensively investigated due to its potent antioxidant properties and demonstrated efficacy against cancer cells. Under certain conditions however, polyphenolic compounds may also exhibit prooxidant activity by elevating intracellular reactive oxygen species (ROS), which can harm the target cells. In this study, we hypothesized that the simultaneous administration of iron (Fe) could alter the antioxidant characteristic of SLM nanoliposomes (SLM Lip) to a prooxidant state. Hence, we first developed a SLM Lip preparation using lipid film method, and then investigated the anti-oxidant properties as well as the cytotoxicity of the liposomal preparation. We also explored the efficacy of concomitant administration of iron sucrose and SML Lip on the tumor growth and survival of mice bearing tumors. We observed that exposing cells to iron, and consecutive treatment with SLM Lip (Fe + SLM Lip) could induce greater toxicity to 4 T1 breast cancer cells compared to SLM Lip. Further, Fe + SLM Lip combination demonstrated a time-dependent effect on reducing the catalase activity compared to SLM Lip, while iron treatment did not alter cell toxicity and catalase activity. In a mouse breast cancer model, the therapeutic efficacy of Fe + SLM Lip was superior compared to SLM Lip, and the treated animals survived longer. The histopathological findings did not reveal a significant damage to the major organs, whereas the most significant tumor necrosis was evident with Fe + SLM Lip treatment. The outcomes of the present investigation unequivocally underscored the prospective use of Fe + SLM combination in the context of cancer therapy, which warrants further scrutiny.

Although the amount of amorphous content in lactose is low, its impact on the performance of a dry powder inhalation formulation might be high. Many formulators and regulatory agencies believe that the levels of amorphous content should be controlled once there is a relationship with the final product performance. This is however not an easy task. The current paper elaborates on multiple challenges and complexities that are related to the control of the amorphous content in lactose. The definition and quantification methods of amorphous lactose are reviewed, as well as challenges related to thermodynamic instability. Additionally, current monographs and recent position papers considering this parameter are discussed to provide an overview of the regulatory landscape. Development of a control strategy is recommended, provided that the amorphous content at a specific moment in the process has shown to have an impact on the performance of the dry powder inhaler.

Metformin (MET), an oral antidiabetic drug, was reported to possess promising anticancer effects. We hypothesized that MET encapsulation in unique nanospanlastics would enhance its anticancer potential against HEP-2 cells. Our results showed the successful fabrication of Nano-MET spanlastics (d = 232.10 ± 0.20 nm; PDI = 0.25 ± 0.11; zeta potential = (−) 44.50 ± 0.96; drug content = 99.90 ± 0.11 and entrapment efficiency = 88.01 ± 2.50%). MTT assay revealed the enhanced Nano-MET cytotoxicity over MET with a calculated IC₅₀ of 50 μg/mL and > 500 μg/mL, respectively. Annexin V/PI apoptosis assay showed that Nano-MET significantly decreased the percentage of live cells from 95.49 to 93.70 compared to MET and increased the percentage of cells arrested in the G0/G1 phase by 8.38%. Moreover, Nano-MET downregulated BCL-2 and upregulated BAX protein levels by 1.57 and 1.88 folds, respectively. RT-qPCR revealed that Nano-MET caused a significant 13.75, 4.15, and 2.23-fold increase in caspase-3, −8, and − 9 levels as well as a 100 and 43.47-fold decrease in cyclin D1 and mTOR levels, respectively. The proliferation marker Ki67 immunofluorescent staining revealed a 3-fold decrease in positive cells in Nano-MET compared to the control. Utilizing the combined Pathway-Enrichment Analysis (PEA) and Reactome analysis indicated high enrichment of certain pathways including nucleotides metabolism, Nudix-type hydrolase enzymes, carbon dioxide hydration, hemostasis, and the innate immune system. In summary, our results confirm MET cytotoxicity enhancement by its encapsulation in nanospanlastics. We also highlight, using PEA, that MET can modulate multiple pathways implicated in carcinogenesis.

Bones are subject to different types of damages ranging from simple fatigue to profound defects. In serious cases, the endogenous healing mechanism is not capable of healing the damage or restoring the normal structure and function of the bony tissue. The aim of this research was to achieve a sustained delivery of rosuvastatin and assess its efficacy in healing bone tissue damage. Rosuvastatin was entrapped into silica nanoparticles and the system was loaded into an alginate hydrogel to be implanted in the damaged tissue. Silica nanoparticles were formulated based on a modified Stöber technique and alginate hydrogel was prepared via sprinkling alginate onto silica nanoparticle dispersion followed by addition of CaCl₂ to promote crosslinking and hydrogel rigidification. The selected nanoparticle formulation possessed high % drug content (100.22$\pm$0.67%), the smallest particle size (221.00$\pm$7.30 nm) and a sustained drug release up to 4 weeks (98.72$\pm$0.52%). The fabricated hydrogel exhibited a further delay in drug release (81.52$\pm$4.81% after 4 weeks). FT-IR indicated the silica nanoparticle formation and hydrogel crosslinking. SEM visualized the porous and dense surface of hydrogel. In-vivo testing on induced bone defects in New Zealand rabbits revealed the enhanced rate of new bone tissue formation, its homogeneity in color as well as similarity in structure to the original tissue.