Unveiling the tyrosinase inhibitory potential of phenolics from Centaurium spicatum: Bridging in silico and in vitro perspectives.

Phenolics, abundant in plants, constitute a significant portion of phytoconstituents consumed in the human diet. The phytochemical screening of the aerial parts of Centaurium spicatum led to the isolation of five phenolics. The anti-tyrosinase activities of the isolated compounds were assessed through a combination of in vitro experiments and multiple in silico approaches. Docking and molecular dynamics (MD) simulation techniques were utilized to figure out the binding interactions of the isolated phytochemicals with tyrosinase. The findings from molecular docking analysis revealed that the isolated phenolics were able to bind effectively to tyrosinase and potentially inhibit substrate binding, consequently diminishing the catalytic activity of tyrosinase. Among isolated compounds, cichoric acid displayed the lowest binding energy and the highest extent of polar interactions with the target enzyme. Analysis of MD simulation trajectories indicated that equilibrium was reached within 30 ns for all complexes of tyrosinase with the isolated phenolics. Among the five ligands studied, cichoric acid exhibited the lowest interaction energies, rendering its complex with tyrosinase the most stable. Considering these collective findings, cichoric acid emerges as a promising candidate for the design and development of a potential tyrosinase inhibitor. Furthermore, the in vitro anti-tyrosinase activity assay unveiled significant variations among the isolated compounds. Notably, cichoric acid exhibited the most potent inhibitory effect, as evidenced by the lowest IC50 value (7.92 ± 1.32 µg/ml), followed by isorhamnetin and gentiopicrin. In contrast, sinapic acid demonstrated the least inhibitory activity against tyrosinase, with the highest IC50 value. Moreover, cichoric acid exhibited a mixed inhibition mode against the hydrolysis of l-DOPA catalyzed by tyrosinase, with Ki value of 1.64. Remarkably, these experimental findings align well with the outcomes of docking and MD simulations, underscoring the consistency and reliability of our computational predictions with the actual inhibitory potential observed in vitro.

Development and Evaluation of Sodium Alginate/Carbopol 934P-Co-Poly (Methacrylate) Hydrogels for Localized Drug Delivery.

This research was carried out to create a pH-responsive polymeric system for the targeted drug delivery of Diloxanide furoate. It relied on sodium alginate (Na-Alg) and Carbopol 934P as building blocks. Using an aqueous free radical polymerization method, SCH1-SCH12 was created with varying polymer, MAA, and MBA input ratios. Positive outcomes were seen in the swelling and release profiles at higher pH levels. Hydrogel formation, as well as component compatibility, thermal stability, and Diloxanide furoate loading, were all validated by instrumental characterization. A drug loading percentage of 83.56% was determined, with the swelling reaching 743.19%. For the formulation with MBA, the gel fraction was 94.58%. The release of diloxanide furoate increased to 91.77% at neutral pH. The formulation containing Carbopol 934P provided the highest mucoadhesion force (3993.42 dynes/cm2). The created hydrogel has been shown to be biocompatible by toxicological testing of the network. Based on the findings, the created polymeric nexus proved promising for pH-dependent localized and regulated delivery of Diloxanide furoate.

Development of a Novel Methotrexate-Loaded Nanoemulsion for Rheumatoid Arthritis Treatment with Site-Specific Targeting Subcutaneous Delivery.

Rheumatoid arthritis (RA) is a systemic, chronic autoimmune disease that causes disability due to progressive inflammation and destruction of the tissues around the joints. Methotrexate is mainly used to prevent the progression of joint destruction and reduce the deformity. The major challenge in treating RA with methotrexate is the systemic side effects that limit dose escalation. Hence, a novel formulation of a methotrexate-loaded nanoemulsion for subcutaneous administration was developed that aims to deliver methotrexate into the system via the lymph. The methotrexate-loaded nanoemulsion was prepared by using the aqueous-titration method. The prepared nanoemulsion was investigated for particle size, surface charge, surface morphology, entrapment efficiency, DSC (differential scanning colorimetry), drug release, hemocompatibility assay, and cytotoxicity, as well as anti-arthritic and stability studies. The vesicle size, zeta potential, PDI (polydispersity index), and entrapment efficiency of the optimized nanoemulsion were 87.89 ± 2.86 nm, 35.9 ± 0.73 mV, 0.27, and 87 ± 0.25%, respectively. The DSC study showed that the crystalline methotrexate was converted to an amorphous form and the drug was fully incorporated into the vesicles. After 72 h, the optimized nanoemulsion showed a drug release of 96.77 ± 0.63%, indicating a sustained-release dosage form. Cytocompatibility testing by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay on macrophage cell lines showed that the nanoemulsion was non-toxic. The formulation showed significant anti-arthritic activity compared to the marketed drug solution. In addition, the nanoemulsion containing methotrexate remained stable for three months when stored at a low temperature. Since the nanoemulsion containing methotrexate has excellent physicochemical properties and lowers systemic side effects by targeted delivery, it is a desirable technology for subcutaneous drug delivery.

Unique Properties of Surface-Functionalized Nanoparticles for Bio-Application: Functionalization Mechanisms and Importance in Application.

This review tries to summarize the purpose of steadily developing surface-functionalized nanoparticles for various bio-applications and represents a fascinating and rapidly growing field of research. Due to their unique properties-such as novel optical, biodegradable, low-toxicity, biocompatibility, size, and highly catalytic features-these materials are considered superior, and it is thus vital to study these systems in a realistic and meaningful way. However, rapid aggregation, oxidation, and other problems are encountered with functionalized nanoparticles, inhibiting their subsequent utilization. Adequate surface modification of nanoparticles with organic and inorganic compounds results in improved physicochemical properties which can overcome these barriers. This review investigates and discusses the iron oxide nanoparticles, gold nanoparticles, platinum nanoparticles, silver nanoparticles, and silica-coated nanoparticles and how their unique properties after fabrication allow for their potential use in a wide range of bio-applications such as nano-based imaging, gene delivery, drug loading, and immunoassays. The different groups of nanoparticles and the advantages of surface functionalization and their applications are highlighted here. In recent years, surface-functionalized nanoparticles have become important materials for a broad range of bio-applications.

Mucormycosis in Indian COVID-19 Patients: Insight into Its Patho-Genesis, Clinical Manifestation, and Management Strategies.

Mucormycosis in patients who have COVID-19 or who are otherwise immunocompromised has become a global problem, causing significant morbidity and mortality. Infection is debilitating and fatal, leading to loss of organs and emotional trauma. Radiographic manifestations are not specific, but diagnosis can be made through microscopic examination of materials collected from necrotic lesions. Treatment requires multidisciplinary expertise, as the fungus enters through the eyes and nose and may even reach the brain. Use of the many antifungal drugs available is limited by considerations of resistance and toxicity, but nanoparticles can overcome such limitations by reducing toxicity and increasing bioavailability. The lipid formulation of amphotericin-B (liposomal Am-B) is the first-line treatment for mucormycosis in COVID-19 patients, but its high cost and low availability have prompted a shift toward surgery, so that surgical debridement to remove all necrotic lesions remains the hallmark of effective treatment of mucormycosis in COVID-19. This review highlights the pathogenesis, clinical manifestation, and management of mucormycosis in patients who have COVID-19.

Formulation and in vivo evaluation of diclofenac sodium sustained release matrix tablet: effect of compression force.

In the present study, Diclofenac Sodium (DS) matrix tablets were prepared by direct compression method under different compression forces (5, 10, 15 and 20 KN), using ethylcellulose as matrix forming material. The produced tablets were characterized on the foundation of satisfactory tablet properties such as hardness, friability, drug content, weight variations and in vitro drug release rate. Differential scanning calorimetry (DSC), Fourier Transform Infrared (FT-IR) spectroscopy and X-ray diffraction have been used to investigate any incompatibilities of the tablet's ingredients. Additionally, in vivo bioavailability has been investigated on beagle dogs. Data obtained revealed that, upon increasing compression force the in vitro drug release was sustained and the T(max) value was four hours (for formulations compressed at 15 and 20 kN) compared to the conventional voltarine(®) 50 tablets (T(max) value of 2 hours).

Controlled-release carbamazepine matrix granules and tablets comprising lipophilic and hydrophilic components.

The objective of this study was to investigate the effect of lipophilic (Compritol 888 ATO) and hydrophilic components (combination of HPMC and Avicel) on the release of carbamazepine from granules and corresponding tablet. Wet granulation followed by compression was employed for preparation of granules and tablets. The matrix swelling behavior was investigated. The dissolution profiles of each formulation were compared to those of Tegretol CR tablets and the mean dissolution time (MDT), dissolution efficiency (DE%), and similarity factor (f(2) factor) were calculated. It was found that increase in the concentration of HPMC results in reduction in the release rate from granules and achievement of zero-order is difficult from the granules. The amount of HPMC plays a dominant role for the drug release. The release mechanism of CBZ from matrix tablet formulations follows non-Fickian diffusion shifting to Case II by the increase of HPMC content, indicating significant contribution of erosion. Increasing in drug loading resulted in acceleration of the drug release and in anomalous controlled-release mechanism due to delayed hydration of the tablets. These results suggest that wet granulation followed by compression could be a suitable method to formulate sustained release CBZ tablets.

Controlled-release carbamazepine granules and tablets comprising lipophilic and hydrophilic matrix components.

The objective of this study was to investigate the effect of lipophilic (Compritol 888 ATO) and hydrophilic components (combination of HPMC and Avicel) on the release of carbamazepine from granules and corresponding tablet. Wet granulation followed by compression was employed for preparation of granules and tablets. The matrix swelling behavior was investigated. The dissolution profiles of each formulation were compared to those of Tegretol CR tablets and the mean dissolution time (MDT), dissolution efficiency (DE %) and similarity factor (f(2) factor) were calculated. It was found that increase in the concentration of HPMC results in reduction in the release rate from granules and achievement of zero-order is difficult from the granules. The amount of HPMC plays a dominant role for the drug release. The release mechanism of CBZ from matrix tablet formulations follows non-Fickian diffusion shifting to case II by the increase of HPMC content, indicating significant contribution of erosion. Increasing in drug loading resulted in acceleration of the drug release and in anomalous controlled-release mechanism due to delayed hydration of the tablets. These results suggest that wet granulation followed by compression could be a suitable method to formulate sustained release CBZ tablets.

Formulation, release characteristics and bioavailability study of oral monolithic matrix tablets containing carbamazepine.

This study examined the release of carbamazepine (CBZ) from hydrophobic (Compritol 888 ATO) and hydrophilic-hydrophobic matrix combination (Compritol 888 ATO-hydroxpropyl methylcellulose, HPMC). Hydrophobic matrix tablets were prepared by hot fusion technique, while hydrophilic-hydrophobic matrix tablets were prepared by wet granulation technique. The properties of the compressed matrix tablets were determined according to the US Pharmacopoeia. Both matrix formulations displayed a controlled-release profile when compared to the reference formulation (Tegretol CR 200). The bioavailability of CBZ formulations and Tegretol CR 200 were evaluated in beagle dogs. Carbamazepine presented a significant higher bioavailability from matrix tablets containing hydrophilic polymer (HPMC) than that obtained from Tegretol CR200. The average inter-subject plasma concentration variability CV% was the least with tablet containing hydrophilic polymer (HPMC) and was the highest with Tegretol CR 200 (33.8 and 54.1, respectively). Analysis of variance applied to log AUC(0-alpha) and log C(max) showed statistical significant differences among the three formulations (P < 0.05). Plotting the fraction of CBZ released in vitro and fraction absorbed showed a statistically significant relationship (R(2) = 0.935-0.975) for the three matrix tablets examined.