Drug Development and Industrial Pharmacy最新文献

Objective: To enhance the anticancer activity of the repurposed drug mebendazole (MBZ) against A549 cell lines by developing nanostructured lipid carriers (NLCs).

Significance: MBZ, an anthelmintic drug, exhibits anticancer properties primarily through the inhibition of Ran GTPase and mitotic spindle assembly. Enhancing its delivery and efficacy via NLC could provide a novel and effective approach for lung cancer treatment.

Methods: NLCs were prepared by mixing different ratios of solid lipid (stearic acid) and liquid lipid (oleic acid) with surfactants and emulsifiers. The NLCs were fully characterized to ensure stability, particle size, zeta potential, and encapsulation efficiency (EE%). The stability of the NLCs was monitored over a 3-week period. The anticancer activity of MBZ-NLCs was evaluated using IC₅₀ assays and in vitro scratch assays.

Results: The NLCs exhibited an average particle size of 300 ± 10 nm and a zeta potential of -27 ± 0.5 mV, indicating good stability. EE% significantly improved from 40% in conventional liposome formulations to 90.7% in NLCs. The anticancer activity of MBZ-NLCs was markedly enhanced, with an IC₅₀ of 62 nM compared to 581 nM for free MBZ, representing a 10-fold increase in potency. Additionally, in vitro scratch assays revealed that MBZ-NLCs effectively prevented cell-cell contact, further supporting their potential for improved therapeutic efficacy.

Conclusion: MBZ-NLCs exhibit significantly improved stability, EE%, and anticancer activity compared to free MBZ. These promising results suggest that MBZ-NLCs could be a potent therapeutic approach for lung cancer treatment, warranting further in vivo studies and exploration of different administration routes.

Objective: To study the efficacy of co-administration of Arshogrit (AG) and Jatyadi Ghrit (JG), two herb-based Ayurvedic medicines, in rat model of croton oil-induced hemorrhoids.

Significance: Hemorrhoids refer to a pathological condition affecting the recto-anal region causing pain, swelling, bleeding and protrusion. The available therapies for hemorrhoids are symptomatic or invasive but are expensive and associated with adverse effects. Hence, there exists a need for efficacious and safer pharmacotherapies.

Methods: Ultra high performance liquid chromatography detected nine phytocompounds in AG and seven in JG. Seven fatty acids were additionally identified in JG by Gas Chromatography-Mass Spectrometry analysis. The in-vivo efficacy of the co-administration of AG, which was administered orally at the doses of 20, 60 and 200 mg/kg/day and JG, which was topically applied (100 mg/animal/day) was evaluated in Wistar rats by inducing hemorrhoids development with the application of croton oil preparation (COP) in the recto-anal area. Prednisolone was employed as the standard drug and was administered orally at the dose of 1 mg/kg/day.

Results: AG and JG were able to attenuate the croton oil-induced macro and microscopic anomalies. Gross pathological observation demonstrated remarkable decrease in croton oil-induced swelling, hemorrhage and formation of pseudomembrane, with the escalating doses of AG. Microscopic observation revealed alleviation in the histopathological lesions (necrosis, inflammation, hemorrhage/congestion, degeneration and dilatation of blood vessels). AG and JG additionally reduced COP-induced increase in the serum levels of pro-inflammatory cytokines.

Conclusion: This study convincingly demonstrates that co-administration of AG and JG is a potential therapy against hemorrhoids, warranting further investigations.

Background: Wu-Lan Thirteen-Flavour decoction (WLTd), a traditional Mongolian medicine, has been used for treating hypertension in clinical practice, but the chemical basis and underlying mechanisms remain unknown.

Methods: The main components of WLTd were identified and quantified using HPLC and UPLC-MS/MS techniques. A compound-target-disease network was constructed using network pharmacology analysis to forecast the potential anti-hypertension targets. In vivo animal and in vitro cellular experiments were performed to validate the efficacy and molecular mechanisms of renal protection of WLTd and its main active components in spontaneous hypertension.

Results: A total of 136 active compounds in WLTd were collected through relevant databases, and network pharmacology analysis identified that the aryl hydrocarbon receptor (AhR) signaling pathway may serve as a potential anti-hypertension targets. Eight of the active components, including vitexin, kaempferol, toosendanin, ursolic acid, matrine, oxymatrine, gardenoside and quercetin, were identified and quantified by HPLC and UPLC-MS/MS. WLTd effectively lowered the mean blood pressure (159.16 ± 13.91 vs 135 ± 13.37 mmHg), reduced the BUN (391.55 ± 59.96 vs 240.88 ± 51.15 mmol/L) and creatinine (1.78 ± 0.41 vs 0.67 ± 0.34 nmol/L) levels, and reduced hypertension-induced renal damage in SHR. AhR and related key gene expression changes predicted by network pharmacology analysis were validated by immunohistochemistry, RT-qPCR, and Western blot analyses. In vitro, studies also showed that WLTd up-regulated AhR expression in angiotensin II-induced HEK293 cell injury.

Conclusions: Wu-Lan Thirteen-Flavour decoction effectively protects hypertension-induced renal injury by regulating the Aryl Hydrocarbon Receptor signaling pathway.

Background: Due to the toxicity and serious side effects of chemical incorporated in topical dosage form used for treatment of wound healing, there is a need to use natural preparation as wound healing preparation.

Aims: Seeds of Trigonella foenum-graecum (TFG) are used to synthesize eco-friendly silver nanoparticles (SNPs) in an appropriate way to heal wounds.

Methods: To synthesize SNPs, TFG was incubated with AgNO₃ to produce SNP-TFG. The obtained SNP-TFG was characterized for their wavelength, size and ζ-potential, surface morphology, and yield production. Then, SNP-TFG was formulated as a topical cream (O/W), characterized, and applied to the rats' groups to examine its wound-healing activity. Finally, a skin biopsy was performed to assess all rats' immunostaining and histopathological (HP) alterations in skin lesions on days 3, 7, 10, and 14.

Results: The prepared SNP-TFG showed non-aggregated nano-formulation, with a λ_max of 396 nm. SNP-TFG recorded a size of 43.65 ± 2.1 nm, a charge of -15.03 ± 3.2 mV, and showed yield of 52.61 ± 1.41% while the release was continued for more than 12 h. During the biosynthesis process, the compounds present in TFG are capable of reducing silver ions (Ag⁺) to form SNPs. SNP-TFG cream showed a pH nearly equal to the skin's pH, with suitable viscosity and homogeneity and an apparent permeability of 0.009 ± 0.001. Further, the HP of the SNP-TFG showed a substantial reduction in wound mass, wound granulation tissue growth enhancement, and epidermal re-epithelialization (proliferation) compared to the control group.

Conclusion: The obtained SNP-TFG is considered a novel skin wound-healing natural and eco-friendly nano-formulation.

Objectives: Nanosuspensions are increasingly recognized as a valuable technology for enhancing poorly water-soluble drugs' solubility and dissolution rate, thereby improving their bioavailability. In this study, we employed ultrasonic-assisted precipitation to fabricate nanosuspensions of indomethacin (IND), utilizing Soluplus^® (Sol) as a stabilizing agent. Our objectives were driven by hypotheses centered on optimizing formulation variables and developing predictive models for optimal IND formulations.

Significance: This research highlights the Box-Behnken design (BBD) as a powerful tool that optimizes the properties of IND nanosuspensions, thus significantly enhancing their dissolution rate.

Methods: The impacts of the independent variables on the mean particle size (MPS), polydispersity index (PDI), and zeta potential (ZP) were investigated using BBD. The optimized nanosuspension was freeze-dried with 3% trehalose to produce a dry nanosuspension (DNS). The DNS was characterized by SEM, DSC, XRPD, solubility, and dissolution.

Results: The IND: Sol ratio and sonication power significantly affected the MPS and ZP of the nanosuspensions. The optimized formulation showed MPS, PDI, and ZP of 144.77 ± 6.68 nm, 0.26 ± 0.08, and -24.6 ± 1.90 mV, respectively. The DNS exhibited spherical particle morphology. The DSC and XRPD confirmed the amorphous state of IND with enhanced solubility and dissolution of IND. DNS showed a 3.7-fold increase in drug release in the first 15 min compared with raw IND.

Conclusions: This study demonstrated the critical role of BBD in accurately predicting the values of independent variables essential for formulating optimal nanosuspensions. These formulations possess specific properties that can be effectively integrated into various dosage forms tailored for different routes of administration.

Objective: The study aimed at designing a pH sensitive Lipid polymeric Hybrid nanoparticle (LPHNP) for targeted release of Paclitaxel (PTX) and Curcumin (CUR) in breast cancer.

Significance: Such systems shall result in controlled triggered release in acidic microenvironment of tumor cells with improved pharmacokinetic profile.

Methods: Chitosan-coated CUR and PTX coloaded pH-sensitive LPHNPs were synthesized employing nanoprecipitation technique. The synthesized NPs were characterized in terms of particle size, polydispersity index (PDI), zeta potential, and morphology.

Results: LPHNPs co-loaded with curcumin (CUR) and paclitaxel (PTX) were successfully formulated, achieving a size of 146 nm, a PDI of 0.18, and an entrapment efficiency exceeding 90%. In vitro release studies demonstrated controlled release of CUR and PTX under tumor pH conditions showing 1.6 fold and 1.7 fold higher release in ABS pH 5 in comparison to PBS 7.4 for PTX and CUR respectively. MTT-assay studies revealed enhanced cytotoxicity of CUR and PTX as LPHNPs showing IC₅₀ value of free CUR & PTX 480.06 µg/mL decreasing to 282.97 µg/mL for CS-CUR-PTX-LPHNPs. In vivo pharmacokinetic evaluations in rats confirmed significantly improved bioavailability, with a 3.8-fold increase in AUC for CUR and a 6.6-fold increase for PTX. Additionally, the LPHNPs demonstrated controlled release and prolonged retention, evidenced by a 2.2-fold increase in the half-life (t1/2) of CUR and a 1.3-fold increase in the half-life of PTX.

The results underscores potential of chitosan-coated LPHNP as a promising delivery platform, offering high drug loading, optimal size for cellular penetration, and prolonged blood circulation for cancer.

Introduction and purpose: Despite the attractive properties of hyaluronic acid (HA), The preparation of HA beads is still challenging. This article reports the preparation of pH-sensitive gel HA beads. The ionic gelation method was used to prepare the HA gel beads using ferric ions. This cross-linking type is based on forming coordination bonds, which enhance the mechanical properties of the prepared beads.

Methods: The developed beads were characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) examined the bead's morphology. Furthermore, the potential of HA gel beads as an oral drug delivery system was investigated using metformin as a hydrophilic model drug. The entrapment efficiency and in vitro, release, and release kinetics were evaluated. The crosslinking density and HA concentration effect on drug release and bead swelling capacity under pH 1.2 and 7.4 were also investigated.

Results: The entrapment efficiency of metformin in HA beads was found to be 79.56 ± 3.89%. FTIR analysis indicated the ionic interaction between ferric ions and the carboxylic groups on the HA molecule. At the same time, there was no substantial interaction between metformin and the polymeric bead. Morphological evaluation and DSC analysis suggested the successful incorporation of metformin within the beads. The in vitro drug release evaluation showed pH-dependent extended release where the release kinetics followed the first-order mathematical model.

Conclusions: This study provides a value-added formulation with the potential for drug delivery use, which can be further investigated for biomedical applications.

Objective: It was aimed to formulate minocyline. HCI loaded electrospun polyurethane/collagen (PU/Col) and polyurethane/collagen/polycaprolactone (PU/Col/PCL) nanofibers are intended for use as a wound dressing.

Methods: The effect of polymer ratio and addition of PCL on the morphology, diameter, drug delivery, encapsulation efficiency, mechanical properties, antibacterial activity against Escherichia coli and Staphylococcus aureus, cytotoxicity, cell adhesion and proliferation were investigated. 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to test the cytotoxicity of the nanofibers on the human dermal fibroblast (HDF) cell line. Cell proliferation/adhesion was also determined by imaging HDF cells seeded on mats with scanning electron microscopy/fluorescence microscopy.

Results: All nanofibers were bead-free and smooth in the diameter range of 866.7-882.4 nm. They had favorable encapsulation efficiency (≥79.3%), controlled drug release up to 24 h and did not have cytotoxic effects. Although collagen was preferred for cell adhesion and proliferation, its spinnability and mechanical properties were poor. While PU improved the spinnability of collagen, its mechanical properties also enhanced with the addition of PCL. Nevertheless, all mats led to favorable cell adhesion and proliferation. All the nanofibers had antimicrobial activity against Escherichia coli and Staphylococcus aureus.

Conclusion: In conclusion, PU/Col and PU/Col/PCL nanofiber mats, which had favorable encapsulation efficiency, controlled drug release and antibacterial activity at least 24 h, cell viability, proliferation, adhesion, mechanical properties to be used as wound dressing, were successfully prepared.

Introduction: Fast melt tablets (FMTs) provide a convenient dosage form that rapidly dissolves on the tongue without the need for water. Cocoa butter serves as a suitable matrix system for FMTs formulation, facilitating rapid disintegration at body temperature.

Objectives: This study aimed to formulate FMTs using cocoa butter as a base and investigate the effect of various disintegrants and superdisintegrants on their characteristics.

Methods: Cocoa butter-based FMTs were prepared via the fusion molding technique. Different disintegrants and superdisintegrants were added at varying concentrations and subjected to characterization. The optimal formulation was selected and incorporated with 10 mg memantine hydrochloride.

Results: The optimal FMT formulation consisted of 340 mg cocoa butter, 75 mg starch, and 75 mg crospovidone, exhibiting a hardness of 17.12 ± 0.31 N and a disintegration time of 32.67 ± 0.17 s. Furthermore, FMTs demonstrated a faster release profile compared to the commercially available product, Ebixa. SEM micrographs revealed homogenous blending of individual ingredients within the cocoa butter matrix and FT-IR analysis confirmed the chemical stability of memantine hydrochloride in the formulation. The dissolution profile of F17 suggested that the drug in FMTs released faster compared to Ebixia. Memantine hydrochloride achieved 98.07% of drug release in FMTs at 10 min. Moreover, the prepared FMTs exhibited stability for at least 6 months.

Conclusion: The successful development of cocoa butter-based FMTs containing memantine hydrochloride highlights the potential of cocoa butter as viable alternative matrix-forming material for FMTs production. This innovative formulation offers patients a convenient alternative for medication administration.