Lornoxicam (LX) is a potent non-steroidal anti-inflammatory drug (NSAID) whose long-term oral administration is limited by gastrointestinal adverse effects. The present study aimed to develop and evaluate LX-loaded proniosomal topical gels as a strategy to enhance dermal permeation and anti-inflammatory efficacy, with direct comparison to a conventional LX gel. LX-loaded proniosomal Gels were formulated by combining lecithin, cholesterol, and a non-ionic surfactant. A conventional gel formulation was also prepared to compare its effectiveness with the proniosomal gel formulation. The vesicle size, Polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency, morphology, in vitro LX release, ex vivo, and finally, the anti-inflammatory efficacy of both formulations was thoroughly characterized. For the proniosomal variants, vesicle sizes were recorded at 373 ± 29 nm for Span 60-based proniosomes (NS) and 230 ± 28 nm for Tween 80-based proniosomes (NT), with corresponding PDI values of 0.23 and 0.31 and zeta potentials of −26 mV and −28 mV, respectively. Encapsulation efficiency exceeded 88% across both formulations. Notably, ex vivo evaluations demonstrated markedly improved skin permeation in the proniosomal gels. The Fluxes measured 51. µg/cm2/h. for NS, 18.7 relative to the standard gel (12.4). These findings were corroborated by anti-inflammatory efficacy studies, which revealed statistically significant improvements with the proniosomal gel (p < 0.05) compared to the standard formulation.

Rosuvastatin is a BCS class II drug effective in the management of atherosclerosis. To enhance solubility and efficacy, Rosuvastatin-β-Cyclodextrin complex-loaded chitosan nanoparticles (R-CD-CNs) were developed. β-cyclodextrin was crosslinked with Citric acid to impart stability to the inclusion complex. Rosuvastatin was incorporated into lyophilized crosslinked β-cyclodextrin by kneading method. R-CD complex was loaded into chitosan-tripolyphosphate nanoparticles. The R-CD-CNs were optimized by 32 full factorial design with independent variables Chitosan, Sodium Tripolyphosphate as crosslinking agent and their effects were checked on dependent variables. Optimized R-CD-CNs showed Particle size 265 ± 17 nm, PDI 0.251 ± 0.02, EE 80 ± 7.5%, and Zeta potential +19.8 ± 3.8 mV. The results of DSC confirmed that drug gets incorporated into chitosan nanoparticles. XRD confirmed amorphous form of drug into chitosan nanoparticles. SEM study confirmed the sphericity of R-CD-CNs. The in vitro release profile was found to be 91 ± 2.5% at the end of 10 h, indicating sustained release characteristics. R-CD-CNs showed a more prominent effect compared to plain Rosuvastatin calcium and the disease control group. The synergistic effect of chitosan was confirmed by the in vivo antihyperlipidemic study. The results of stability study reveal good stability of R-CD-CNs. R-CD-CNs were developed successfully and will be helpful for the effective management of hyperlipidemia.

Nanozymes are engineered nanoparticles that mimic enzyme-like catalytic activities and have gained significant attention in bioanalytical and biomedical applications. A broad range of nanomaterials has been explored for their intrinsic catalytic properties, and with suitable optimization, these systems can exhibit enzyme-comparable activity in biological environments. Consequently, nanozymes offer substantial potential as versatile catalytic platforms in nanomedicine. This review highlights recent advances in nanozyme research, emphasizing mechanistic understanding rather than strict kinetic equivalence to natural enzymes. Fundamental catalytic principles, including electron transfer, redox cycling, and surface-confined active-site behavior, are discussed to elucidate nanozyme function in complex biological systems. Particular focus is placed on the influence of structural features, surface functionalization, and cascade catalytic architectures on the activity of metal oxide- and carbon-based nanozymes. In addition, nanozymes responsive to tumor microenvironmental stimuli such as pH, hydrogen peroxide, and glutathione are examined for targeted redox modulation. Pharmacokinetic behavior and biosafety considerations are critically evaluated, addressing unresolved concerns related to long-term toxicity and biodistribution. Overall, nanozymes represent a promising class of catalytic nanomaterials for future nanomedicine platforms, provided systematic efforts ensure mechanistic rigor, standardized evaluation, and regulatory-aligned safety assessment.

Ledipasvir is one of the direct-acting antiviral agents used for treating hepatitis C virus (HCV) infection. To achieve dose reduction and cost-effective therapy, this study aimed to enhance the interaction of ledipasvir with HCV-infected hepatocytes through the development of cationic bilosomes (CBs) and galactosylated bilosomes (GBs). These delivery systems were designed to promote hepatocellular targeting via the asialoglycoprotein receptors (ASGPRs). Eight bilosomal formulations were developed by the ethanol injection method following a 2³ full factorial design, and numerical optimization using Design Expert® software identified the optimized formulation. In parallel, galactosylated stearylamine (GSA) was synthesized through conjugation of stearylamine (SA) with lactobionic acid (LB). The successful synthesis of GSA was verified through FTIR and 1H NMR spectroscopic analyses. SA and GSA were subsequently incorporated into the optimized bilosomes to obtain CBs and GBs, respectively. The prepared systems were evaluated for particle size, polydispersity index, entrapment efficiency, and zeta potential, and their morphology was identified using transmission electron microscopy. Following 8-h incubation with HepG2 cells, CBs and GBs achieved significantly higher cumulative cellular uptake of ledipasvir (31.79% ± 3.11% and 20.62% ± 2.12%, respectively) compared to the ledipasvir free dispersion (11.02% ± 3.02%). These findings highlight CBs and GBs as promising nanocarriers for targeted delivery of ledipasvir to hepatocytes.

Redox-responsive nanocarriers exploit the unique intracellular redox environment to enable targeted and controlled release of therapeutic agents. The present study comprises the fabrication of Palbociclib-bearing Bovine serum albumin-based redox-responsive nanoparticles (RR-PAL-NPs) through self-crosslinking using the desolvation technique. The optimisation of the formulation was achieved using the Box–Behnken design of experiment. The RR-PAL-NPs particle size, PDI, zeta potential, and percentage entrapment efficiency are 195.56 ± 9.99 nm, 0.22 ± 0.01, 3.9 ± 0.12 mV, and 91.23 ± 3.8%, respectively. In the presence of 10 mM glutathione, at pH of 5.5 and 7.4, nearly all the PAL was released from RR-PAL-NPs, making a release of 88.98 ± 3.00 and 82.41 ± 3.9%, respectively. Furthermore, dilution study, turbidimetric analysis, UV and spectrofluorescence analysis, circular dichroism, stability study, pH titration, and hemocompatibility study were also performed, which deemed the formulation satisfactory. RR-PAL-NPs depicted an exceptional in vitro cytotoxic and apoptotic profile. An outstanding mitochondrial depolarisation, ROS generation, inhibition of colony formation, wound healing, and glutathione depletion were seen. In the 3D mammosphere study, it caused a 3.57-fold reduction in the 3D mammosphere diameter as compared to PAL, along with higher apoptosis and uptake efficiency. Immunofluorescence assays depicted an upregulation of BAX and downregulation of Bcl2 protein expression. In the cell cycle study, the RR-PAL-NPs showed remarkable G0/G1 phase arrest due to the decreased phosphorylation of retinoblastoma protein.

Persistent postoperative pain is commonly occurred after surgical procedures, while over half of patients suffer from poorly controlled pain, due to the limited therapeutic period of commercial drugs and suboptimal drug delivery strategy. Herein, an injectable sustained-release gel was developed by a combination of ropivacaine (a local anesthetic) and lornoxicam (a nonsteroidal anti-inflammatory drug), which formulated by poly(ortho esters) (POE) to regulate the sustained-release behavior. POE with low molecular weight was synthesized and employed to prepare the ropivacaine and lornoxicam sustained-release gel (RL-SRG) with the rheological characteristics of temperature-sensitivity. In vitro release studies demonstrated that RL-SRG exhibited sustained release for 72 h. The RL-SRG was stable for 3 months at 40 ± 2 °C and a relative humidity of 75 ± 5%. In vivo pharmacokinetic studies in rats indicated that RL-SRG maintained the plasma concentrations of ropivacaine and lornoxicam for 3 days. Compared to commercial products, RL-SRG prolonged the time of peak concentration (T max), mean residence time (MRT), and elimination half life (t 1/2), as well as possessed similar the area under the plasma concentration–time curve (AUC0– t ). Therefore, RL-SRG has been validated as a novel sustained release system to the application for the long-term treatment of postoperative pain.

Coenzyme Q10 (CoQ10) is an essential molecule that plays a role in mitochondrial oxidative phosphorylation and acts as a powerful antioxidant. In this study, CoQ10-loaded nanofibers were developed and characterized via electrospinning method. SEM analyses showed that the fiber diameters ranged between 487 and 2163nm, and that CoQ10 loading did not disrupt the fiber structure but reduced the diameter. It was determined that bead formation was observed only in the F1 formulation due to the low viscosity (73.09mPas) and conductivity (1.66mS/cm) values. The F4 formulation, containing Eudragit RL100 and Kollidon 90F, was selected as the final formulation because it exhibited the highest tensile strength (1.49MPa) and the smallest fiber diameter (1306nm). In vitro drug release studies demonstrated that the F4 formulation released only 4% of CoQ10 within 24 hours, indicating a controlled release profile. The biocompatibility of this formulation was evaluated through a cytotoxicity assay using the SH-SY5Y neuroblastoma cell line. After seven days of treatment, the CoQ10-loaded nanofiber group showed a cell viability of 101.65%. This result indicates that the nanofibers did not exhibit any cytotoxic effect; on the contrary, they demonstrated potential to support cell proliferation. These findings suggest that CoQ10-loaded nanofibers hold promise for biomedical applications.

Pyrazinamide (PYZ), a nicotinamide derivative, is an essential first-line anti-TB drug. However, its dose-dependent hepatotoxicity poses a considerable challenge, accentuating the need for improved delivery approaches. The key objective of the research work was to develop mannose-appended pyrazinamide-containing solid-lipid nanoparticles (Mn-PYZ-SNs) for the targeted management of TB. The developed Mn-PYZ-SNs depicted a particle size of 422±09 nm, which was slightly higher than that of unconjugated PYZ-SNs (Un-PYZ-SNs)(401±08 nm), with a minimal reduction in entrapment efficiency(83.64±1.42%). The in vitro drug release studies demonstrated comparable sustained release patterns for both formulations, with a similarity factor (f2) of 77.33, indicating that the structural integrity of PYZ-SNs was maintained during mannose conjugation. Fluorescence imaging and flow cytometric analysis revealed significantly enhanced cellular uptake of Mn-C6-SNs, with a 1.60-fold increase compared to Un-C6-SNs. The in vivo pharmacokinetic studies conducted on Sprague-Dawley rats showed a 4.7-fold improvement in relative bioavailability for Mn-PYZ-SNs. Biodistribution studies demonstrated significantly higher lung accumulation of Mn-PYZ-SNs (1.93-fold) compared to Un-PYZ-SNs at 24 hours. The aforementioned results imply that the developed Mn-PYZ-SNs could be a promising carrier for the treatment of TB. via the oral intestinal lymphatic pathway, circumventing its hepatic first-pass metabolism, and thereby preventing hepatic adverse effects.

The goal of this study was to explore the fabrication of a combination drug product containing two poorly soluble active pharmaceutical ingredients (APIs), carvedilol (CAR) and simvastatin (SIM), in therapeutically relevant doses (25 mg of each API) with a distinct, easily distinguishable shape. Fused deposition modeling, combined with hot-melt extrusion (HME), was used to produce hollow heart-shaped dual-loaded tablets in which the two APIs were spatially separated with an intermediate API-free layer. Water-soluble hydroxypropyl methylcellulose of varying molecular weights was used as the primary polymer for HME. The incorporation of a processability-improving polymer, such as polycaprolactone, was necessary to facilitate the printing of these delicate geometries and lower the printing temperature. The 3D-printed tablets contained the therapeutic doses of both APIs; however, further optimization of manufacturing processes is required to improve drug content uniformity. The drug release from the printed tablets was sustained, with complete release of CAR observed after 24 h, demonstrating the suitability of the designed drug products for oral delivery.

Alzheimer’s disease (AD) is a neurodegenerative disease that is associated with neuroinflammation. Dextromethorphan (DXM) exerts neuroprotective effects in many central nervous system injuries and neurodegenerative diseases. The cell wall of Saccharomyces cerevisiae is a cell-based drug delivery system that can be a suitable candidate for targeted drug delivery to the site of inflammation. In this study, nanoparticles (NPs) were prepared from Saccharomyces cerevisiae cell walls, coated with polysorbate-80, and loaded with DXM. NPs had favorable hemolytic behavior with a particle size distribution of 187.25 ± 73.37 nm and a zeta potential of +4.3 mV. Pathological examination in a mouse model of neuroinflammation showed that NPs had the ability to reduce brain inflammation and the adverse effects of DXM.