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Citrus flavanone (naringenin)-infused transferosome based gel: Development, optimization, characterization with an exploration of diabetic wound healing potential through an integration of network pharmacology, in vitro and in vivo studies
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Flavonoids are widely used natural phenolic compounds, which have shown potential role in wound healing. Many pre-clinical studies have indicated that flavonoids are one of the most promising and important group of natural compounds which can be used to treat acute as well as chronic wounds. Flavonoids can be classified as flavones, isoflavones, flavonols, flavanols, flavanones and anthocyanins respectively. Naringin, the glycone part and naringenin the aglycone part falls under the broad umbrella of flavonoid class (flavanones) which are majorly obtained from various citrus fruits like lemon, orange, grapefruit. Several therapeutic roles have been documented for naringenin, such as anti-inflammatory, antioxidant, antiulcer, anticancer, wound healing activities. Due to challenges in solubility, it is crucial to encapsulate these compounds using nanotechnological platform to deliver and make them bioavailable for the treatment of several diseases. Nanocarriers like transferosomes act as self-adaptable ultra-deformable flexible bilayer vesicles composed of phospholipid and edge activators along with hydration media. The present study has focused on the beneficial role of the flavonoid naringenin with a special emphasis on naringenin encapsulated transferosomal gel towards healing of different diabetic wound conditions and exploring their underlying mechanisms. Quality by design (QbD) employing design expert software to optimize transferosomes and further Dynamic light scattering (DLS) studies, Field emission scanning electron microscopy (FESEM), Fourier-transformed infrared spectroscopy (FT-IR) analysis, X-ray diffraction (XRD) studies, Rheology studies, Percentage entrapment efficiency followed by In vitro drug release studies for naringenin encapsulated transferosomal gel has been evaluated. Development of naringenin embedded transferosomal gel has been carried out along with its in vitro antioxidant, antimicrobial activity evaluation followed by in vivo wound healing studies.

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Development of Folate Receptor (FR-α) Mediated Nano Carrier Sustained Release Formulation for Ameliorating Colorectal Cancer

Background: Colorectal cancer (CRC) remains a significant global health concern, ranking as the third most common cancer worldwide and the second leading cause of cancer-related mortality. The folate receptor-alpha (FR-α), a glycosylphosphatidylinositol (GPI)-anchored membrane protein, this overexpression presents a compelling opportunity for targeted drug delivery. Aim: This research aimed to develop an FR-α targeted nanocarrier system for the precise delivery of an anticancer agent, thereby minimizing off-target effects and systemic cytotoxicity to normal cells. Methodology: The targeted nanocarrier formulations were prepared by conjugating folic acid (FA)/Premetrexed and anticancer agents . Polymeric micelles were developed using an ethanol injection method to achieve a sustained-release formulation. Various excipients and block polymeric materials, including Pluronic P123, D1 lipids, and Transcutorl HP, were utilized. The final formulations were rigorously characterized for particle size, surface charge (zeta potential), morphology, drug loading efficiency, and in vitro drug release kinetics. Furthermore, the cellular inhibitory effects and cytotoxicity were evaluated in vitro against colon cancer cell lines (CT-26 and HT29) and a normal human embryonic kidney cell line (HEK 293). Results: The formulations demonstrated nano size particle range (500 ± 25 nm) and a sustained drug release, with ~ 67 ± 5% of the drug released over 72 hours in PBS (pH 7.4). High drug loading efficiency of 73 ± 2% was achieved, indicating a significant payload capacity. In cellular studies, the targeted formulations achieved 50% cell inhibition (IC50) at a concentration of 0.250 µM, significantly lower than the 0.585 µM observed for non-targeted formulations. Critically, the targeted formulations exhibited markedly reduced cytotoxicity in the normal HEK 293 cell line. Conclusion: Our findings reveal that the FR-α targeted drug delivery system effectively ameliorates colon cancer, even at advanced stages.​ We also find the challenges in conjugation rection, however more hypothetical experiments would be required to establish the chemical conjugation. Upon this issue we had used pemetrexed as potent antifolate ligand instead of folic acid.

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Development of a method for obtaining and quality control of composites nanostructured with AgNPs particles for promising medical applications

Introduction. This paper examines current aspects of the development and medical introduction of new disinfectants based on heterogeneous surface matrices exhibiting microbicidal activity, in the context of increasing resistance to existing drugs. A comprehensive approach is proposed for characterizing the properties of the synthesized matrix samples using both pharmacopoeial techniques and original methods . The purpose of this study was to develop, synthesize, and analyze materials with surface antimicrobial properties based on metallic silver nanoparticles (AgNPs). The study objects included: A nanodispersion containing metallic silver particles (AgNPs) synthesized by the citrate method using a 2 mM AgNO₃ solution (pH 5.4), 0.15 M sodium citrate, and 0.15 M glucose at 60°C; The formation of AgNPs was monitored by UV-Vis spectroscopy by sampling aliquots every 5 minutes during synthesis; A heterogeneous solid medical Paraffinum served as a model material with . It was prepared by adding an AgNPs suspension to molten paraffin (approximately 0.5 cm layer), continuously heated by a horizontal element, using spraying under mixing mimicking vortex water-oil emulsification. After synthesis, the nanostructured heterogeneous paraffin (NGP) sample was left to solidify completely. To assess the quality of both the nanodispersion and NGP, the following methods were applied: Dynamic Light Scattering (DLS, Zetasizer Nano ZS), UV-Vis spectroscopy (Agilent Cary 300), and surface diffuse reflection analysis. Results. The AgNPs in the nanodispersion exhibited an average particle size of approximately 150 nm (intensity distribution). The UV absorption peak at 440 nm corresponds to surface plasmon resonance and 4d‒5sp interband electronic transitions. Chemometric analysis of speckle patterns formed by diffuse reflection from the heterogeneous surface provided a unique descriptor distribution enabling qualitative identification. Conclusions. he results may be valuable for the pharmaceutical industry in the synthesis, quality control, and application of new bactericidal systems. Funding: This research was supported by a grant from the RUDN University Strategic Academic Leadership Programme No. 033320–2-000.

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Conventional and Galactosylated Liposomal Formulations of Ellagic Acid for the Modulation of Cellular Senescence

Ellagic acid (EA) is a natural polyphenolic compound mainly present in Punica granatum L. It has gained increasing interest for its antioxidant and anti-senescence properties, with documented benefits in models of cardiovascular, renal, and neurodegenerative aging. However, its clinical application is hindered by very low aqueous solubility (9.7 µg/mL), poor bioavailability, and limited stability.

This study aimed to overcome these limitations by developing a liposomal formulation (LP-EA), further functionalized with a galactose derivative (Gal-LP-EA) for selective delivery to senescent cells. This targeting strategy exploits the overexpression of β-galactosidase, which cleaves the galactose–liposome bond, enabling the intracellular release of EA specifically in pathological cells.

LP-EA and Gal-LP-EA were prepared by thin-film hydration method and physicochemically characterized for particle size, polydispersity index (PdI), zeta potential, morphology, and encapsulation efficiency (EE%). Stability was assessed over 30 days at controlled temperatures, and in vitro release profile was investigated using the dialysis bag method. Passive permeability across the blood–brain barrier (BBB) was evaluated by PAMPA test.

Encapsulation of EA into LP increased its solubility by approximately 56-fold. LP-EA and GAL-LP-EA showed size, PdI and Zeta potential of 113.2±0.91 nm, 0.21±0.00 and -24.57±0.43 mV and 110.8±0.17 nm, 0.21±0.02 and -24.04±0.04 mV, respectively. EE% was around 80% for both formulations. The physicochemical properties were stable through the study period. Moreover, LP provided a sustained and gradual release over 24 h (~30%), avoiding the burst effect observed for EA solution (52% at 2h), following the Fickian diffusion mechanism. Liposomal formulations significantly enhanced EA BBB permeation, as evidenced by an approximately one order of magnitude increase in the permeability coefficient.

These results indicate that LP improved EA solubility, stability and controlled release, facilitating its transport across the BBB. Thus, GAL-LP-EA could represent a promising nanomedicine-based strategy for age-related diseases.

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IVERMECTIN LOADED SOLID LIPID NANOPARTICLES FOR OVARIAN CANCER TREATMENT: DEVELOPMENT, CHARACTERIZATION AND ENHANCED CYTOTOXIC ACTIVITY

Introduction: The ivermectin is a broad-spectrum antiparasitic drug from the avermectin family, has recently gained attention for its potential anticancer properties. This study focuses on the formulation development of ivermectin-loaded solid lipid nanoparticles (Iv-SLNs) and evaluating release kinetics and nano-sized formulation effect in ovarian cancer cells.

Methods: The Iv-SLNs were formulated using Box-Behnken experimental design and characterized in terms of physicochemical properties (particle size, zeta potential, polydispersity index, and entrapment efficiency), drug release profile, and release kinetics. The anticancer activity of Iv-SLNs was assessed in OVCAR-3 cells and compared to ivermectin in suspension form (Iv-SUSP).

Results: The Iv-SLN formulation was characterized by particle size (154.5 ± 41.3 nm), polydispersity index (0.204 ± 0.02), zeta potential (-17.4 ± 3.93 mV), and entrapment efficiency (81.34 ± 5.67%) respectively. Release kinetics indicated that Iv-SLNs act as a sustained release system and adhering to Higuchi kinetics (r2 = 0.981). In-vitro cytotoxicity studies showed that Iv-SLNs exhibits enhanced anti-cancer effect on OVCAR-3 cells than ivermectin suspension (2.1-fold).

Conclusion: Nano drug delivery systems offer advantages such as biocompatibility, enhancing drug’s solubility, improving drug’s bioavailability, and targeted drug delivery, which may help overcome drug resistance and improve treatment efficacy. This study highlights Iv-SLNs as a promising nano-sized drug delivery system for ivermectin, and potentially enhancing its effectiveness in ovarian cancer therapy.

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Synergistic triple drug co-loaded nanoplatforms for improved cancer treatment

Cancer remains one of the leading causes of death worldwide. Current therapies often have relevant limitations, including low selectivity to tumor tissues, leading to systemic toxicity, and treatment resistance development. In recent years, however, nanotechnology has emerged as a promising approach to improving drug delivery, offering enhanced tumor targeting, better pharmacokinetics and fewer side effects. Additionally, making use of different pharmacological action mechanisms, delivering more than one drug molecule simultaneously can lead to synergistic or additive therapeutic effects. In this context, a scientific literature review was performed, exploring experimental studies that use nanocarriers for triple drug co-delivery in cancer treatment. The analyzed studies employed well-established chemotherapeutic agents and non-classical anticancer agents, such as 2′-deoxy-5-fluorouridine 5′-monophosphate, 5-fluorouracil, alpha-lipoic acid, camptothecin, chlorambucil, cisplatin, combretastatin A4, crizotinib, curcumin, doxorubicin, ellagic acid, erastin, fluvastatin, gemcitabine, honokiol, irinotecan, leucovorin, palbociclib, paclitaxel, pemetrexed, rosuvastatin, sildenafil, silybin, small interfering RNA against programmed death-ligand 1 platinum-based cross-linker, tariquidar, verteporfin, and zinc(II) phthalocyanine. These therapeutic agents were formulated within nanocarriers such as polymeric nanoparticles, polymeric micelles, dendrimers, PEGylated liposomes, lipid–polymer hybrids and inorganic nanoparticles. Each nanocarrier type offers specific advantages in terms of drug loading, drug release control and targeting ability. Overall, this review supports the idea that triple-drug nanocarrier-based strategies are powerful, evolving tools for developing more effective cancer therapies. These strategies offer enhanced synergistic effects, increased therapeutic precision and the potential to modulate the tumor microenvironment.

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ADVANCED TECHNOLOGIES OF THE TWO-DIMENSIONAL DIFFUSE REFLECTION METHOD IN PHARMACEUTICAL QUALITY CONTROL
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In the current context of viral variability driven by their high mutability, comprehensive measures for prevention, control, and treatment with effective antiviral agents are required, along with the development of rapid and reliable methods for quality control. This work is based on an approach employing the kinetics of diffuse light reflection (DLR) from a rough surface, followed by chemometric processing of dynamic speckle patterns. To this end, mathematical descriptors analogous to QSAR models were incorporated into the calculation algorithm: Wiener (W) and Balaban (J) indices in the Trinaystich modification—d1, d2, d3—as well as two triads of root-mean-square deviations sd1, sd2, sd3; r1, r2, r3 (where ri=di/sdi) and . The aim of the study was to develop and validate an analytical method based on 2D-DLR for the quantitative assessment of antiviral drug substances. Materials and Methods. Ribavirin (manufacturer Jiangling Benda Pharmaceutical Co., China) — a synthetic nucleoside analog with prominent antiviral activity and antimetabolic properties; model aqueous solutions (concentrations ranging from 0.25 mg/mL to 5 mg/mL), n=6n=6; proprietary software (Vidan®). Results. A family of 10 descriptors, represented as sequential horizontal bands on the 2D diagram (with didi corresponding to concentration, µg/mL), demonstrated stability of values for a specific sample within intra-laboratory reproducibility, and differentiation among samples with different solution dilutions. Particularly illustrative and statistically significant was the result for the topological descriptor R (correlation coefficient r=0.9998). This enabled the construction of a calibration curve in the coordinates “R-concentration (µg/mL),” based on the linear equation y=170.4+55.7⋅xy=170.4+55.7⋅x, with r=0.982. The method was validated according to ICH Q2 (R1) guidelines, confirming linearity, accuracy (RSD = 7.19%), and repeatability (n=6, P=0.95). The repeatability error (εε) was determined to be 7.55%, indicating acceptable analytical variability. Conclusion. The 2D-DLR method demonstrated reliability for systematic quantification of concentration of the antiviral ribavirin in aqueous solutions.

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Photodynamic inactivation of Candida albicans in different growth forms mediated by BODIPY derivatives

Candida albicans is an opportunistic fungal pathogen that normally exists as a commensal on human skin and mucosal surfaces, but under certain conditions it can develop virulence factors and exhibit antifungal resistance. Photodynamic inactivation (PDI) has emerged as a promising non-conventional approach to control this microorganism. In this study, the PDI activity of two BODIPY derivatives: a compound bearing a dimethylaminopropoxy group attached to a phenylene unit (BDP 1) and its dibrominated analogue (BDP 2) were evaluated against C. albicans in different growth forms. In planktonic cultures, 5.0 µM BDP 1 completely inactivated 1×106 and 1×107 CFU/mL after 30 min of white light irradiation (90 mW/cm2). The same effect was achieved with only 0.25 µM BDP 2 after an irradiation of 15 min. Additionally, a ~2 log reduction was observed in cultures containing 1×108 CFU/mL treated with 5.0 µM BDP 2 and 30 min of irradiation. Mechanistic assays revealed that BDP 1 mainly acts via type I photoprocesses, while BDP 2 predominantly generates singlet molecular oxygen. In pseudohyphae suspended in PBS, 1.0 µM BDP 1 with 15 min of irradiation completely abolished viability, whereas BDP 2 required only 2 min for the same outcome. In biofilms, BDP 1 produced ~1.5 log viability reductions after 60 min of white light. In contrast, BDP 2 caused ~2 log and ~3 log reductions in 18 h old biofilms at 5.0 and 10.0 µM, respectively, and completely eradicated cells when 10.0 µM was applied during proliferation followed by 60 min irradiation. These findings highlight the superior performance of BDP 2 across all C. albicans morphologies, underscoring its potential as an effective photosensitizer for antifungal PDI strategies.

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Porphyrin-based polymers for antifungal photodynamic inactivation of Candida albicans

Fungal infections are a growing health concern, associated with high mortality rates, elevated treatment costs, and an increasing number of hospitalized patients. Consequently, novel therapeutic strategies are urgently needed. In this work, two porphyrin-based polymers, PTPPF16-DAB and PZnTPPF16-DAB, were evaluated as photosensitizers for the photodynamic inactivation (PDI) of Candida albicans. These polymers are constructed from 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TPPF20) or its Zn(II) complex (ZnTPPF20) as porphyrinic units, and N,N,N',N'-tetrakis(3-aminopropyl)-1,4-butanediamine (DAB) as a multifunctional crosslinker. Planktonic yeast suspensions (1 × 106 CFU/mL) in PBS were treated with the polymers (2.5 or 5.0 µM) for 30 min in the dark. Both polymers rapidly bound to yeast cells within 5 min. Complete elimination of planktonic C. albicans was achieved at 5.0 µM after 30 min of irradiation. Experiments with reactive oxygen species scavengers confirmed that singlet molecular oxygen was the main species involved in the photoinactivation process. These polymers were also effective to photoinactivate C. albicans pseudohyphae in PBS, producing a concentration and time-dependent effect with both polymers. A complete loss of cell viability was observed when the cultures were treated with 5.0 µM. The most pronounced inhibitory effects on biofilms occurred when the polymers were incorporated during the proliferation phase. Against 18-h biofilms, PTPPF16-DAB achieved a ~2.3 log reduction, whereas PZnTPPF16-DAB was more effective during the adhesion phase, reducing viability by ~2 log. These results suggest that the antifungal performance of the polymers varies according to the metabolic activity and structural organization of C. albicans biofilms. The results indicate that both porphyrin-based polymers have potential applications as phototherapeutic agents for fungal inactivation under different culture conditions.

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Mechanistic Insights into Drug Release and In Vitro Pharmacokinetics –Vildagliptin, Fast Disintegrating Tablets with Superdisintegrants

Objective: Fast-disintegrating tablets (FDTs) have gained significant attention in pharmaceutical research due to their ability to disintegrate rapidly in the oral cavity without the need for water. This improves patient compliance, particularly in pediatric and geriatric populations. The present study formulated and evaluated FDTs using various Superdisintegrants to enhance drug dissolution and bioavailability.

Methods: The tablets were prepared by direct compression, employing sodium starch glycolate, croscarmellose sodium, and crospovidone as Superdisintegrants at different concentrations. A comprehensive preformulation study assessed the powder blend’s flow properties, including bulk density, tapped density, Carr’s index, Hausner’s ratio, and angle of repose, to ensure uniformity and ease of compression. Post-compression evaluation of the tablets involved weight variation, hardness, friability, thickness, disintegration time, and content uniformity to determine their physicochemical properties.

Results: The results revealed that all formulations exhibited satisfactory pre-compression and post-compression characteristics. However, formulation F6 (containing 15 mg of crospovidone) had the shortest disintegration time (3 min 10 s) and the highest drug release (99.56% in 30 minutes) compared to the other formulations. F6 also showed the lowest friability (0.11%), indicating excellent mechanical strength; its content uniformity was highest (99.81%), ensuring uniform drug distribution in each tablet. In vitro dissolution studies demonstrated that drug release significantly improved with increasing superdisintegrant concentration, with crospovidone being the most effective among those tested. Kinetic analysis indicated that the formulations followed zero-order release kinetics and fit the Higuchi diffusion model, suggesting a diffusion-controlled release mechanism. Based on these findings, the optimized formulation (F6) was identified as the most promising due to its rapid disintegration, enhanced dissolution rate, and superior mechanical properties.

Conclusion: This study highlights the significance of selecting an appropriate superdisintegrant to achieve optimal tablet performance. The use of crospovidone at 15 mg was the most effective in producing FDTs with excellent pharmaceutical characteristics. Formulation F6 is recommended for further in vivo evaluation and potential commercialization, offering significant advantages in improving drug bioavailability and patient compliance.

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