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The application of intra-articular injections in osteoarthritis management has gained great attention lately. In this work, novel intra-articular injectable hyaluronic acid gel-core vesicles (hyaluosomes) loaded with diacerein (DCN), a structural modifying osteoarthritis drug, were developed. A full factorial design was employed to study the effect of different formulation parameters on the drug entrapment efficiency, particle size, and zeta potential. Results showed that the prepared optimized DCN- loaded hyaluosomes were able to achieve high entrapment (90.7%) with a small size (310 nm). The morphology of the optimized hyaluosomes was further examined using TEM, and revealed spherical shaped vesicles with hyaluronic acid in the core. Furthermore, the ability of the prepared DCN-loaded hyaluosomes to improve the in vivo inflammatory condition, and deterioration of cartilage in rats (injected with antigen to induce arthritis) following intra-articular injection was assessed, and revealed superior function on preventing cartilage damage, and inflammation. The inflammatory activity assessed by measuring the rat’s plasma TNF-α and IL-1b levels, revealed significant elevation in the untreated group as compared to the treated groups. The obtained results show that the prepared DCN-loaded hyaluosomes would represent a step forward in the design of novel intra articular injection for management of osteoarthritis.

The anti-hyperglycemic sodium glucose co-transporter 2 inhibitor Canagliflozin (CFZ) represents a recent antihyperglycemic modality, yet it suffers from low oral bioavailability. The current work aims to formulate CFZ-loaded transdermal nanostructured liquid crystal gel matrix (NLCG) to improve its therapeutic efficiency. Pre-formulation study included the construction of pseudoternary phase diagrams to explore the effect of two conventional amphiphiles against amphiphilic tri-block copolymer in the formulation of NLCG. The influence of different co-solvents was also investigated with the use of monooleine as the oil. Physical characterization, morphological examination and skin permeation were performed for the optimized formulations. The formula of choice was further investigated for skin irritation and chemical stability. Pharmacodynamic evaluation of the successful formula was conducted on hyperglycemic as well as normoglycemic mice. In addition, oral glucose tolerance test was conducted. Results revealed the supremacy of Poloxamer for stabilizing and maximizing liquid crystal gel (LCG) area percentage that reached up to 12.6%. CFZ-NLCG2 isotropic formula showed the highest permeation parameters; maximum flux value of 7460 μg/cm 2  h and Q 24 of 5327 μg/cm 2 . Pharmacodynamic evaluation revealed the superiority of the antihyperglycemic activity of CFZ-NLCG2 in fasting mice and its equivalence in the oral glucose tolerance test (OGTT) compared to the oral one. The obtained results confirmed the success of CFZ-NLCG2 in the transdermal delivery of CFZ in therapeutically effective concentration compared to the oral route, bypassing first pass effect; in addition, eliminates the possible gastrointestinal side effects related to the inhibition of intestinal sodium glucose co-transporter (SGLT) and maximizes its selectivity to the desired inhibition of renal SGLT.

Osteoarthritis (OA) is regarded as one of the most prevealent irreversible joint degenerative disorder worldwide. Recently, considerable interest in utilizing intra-articular (IA) injections for managing OA has been raised. In this study, IA injectable surface modified iron oxide microparticles (SMIOMPs) loaded with Diacerein (DCN) were developed. The effects of formulation parameters on particle size, entrapment efficiency, and zeta potential were explored using factorial design. The optimized formulation was characterized regarding morphology and in vitro release. Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) were done to assess interactions. Further, sterilization and performance in rats with induced arthritis has been performed for the optimized formulation. The selected optimized system included 2M FeCL3 and 1% chitosan as a surface modifier achieved high drug entrapment of 85.25% with a PS of 1.54 µm and sustained DCN release. Morphological examination of the optimized formulation revealed spherical particles with chitosan coat. DSC and FTIR results indicated the absence of undesired interactions between DCN and the used components. No significant change in the measured parameters was observed following sterilization using gamma radiation. assessment revealed superior performance for the optimized formulation in reducing cartilage inflammation and degradation. Plasma levels of tumor necrosis factor α and Interleukin-1 beta, as well as knee diameter, were significantly reduced in the treated groups compared to the untreated ones. Overall, the results suggest that the proposed DCN-loaded SMIOMPs represent a promising advancement in the arena of cartilage regeneration.

The aim of this work was to develop a novel and more efficient platform for sublingual drug delivery using mosapride citrate (MSP) as a model drug. The engineering of this delivery system had two stages, the first stage was tuning of MSP physicochemical properties by complexation with pure phosphatidylcholine or phosphatidylinositol enriched soybean lecithin to form MSP-phospholipid complex (MSP-PLCP). Changes in physicochemical properties were assessed and the optimum MSP-PLCP formula was then used for formulation into a flushing resistant platform using two mucoadhesive polymers; sodium alginates and sodium carboxymethylcellulose at different concentrations. Design of experiment approach was used to characterize and optimize the formulated flushing resistant platform. The optimized formulation was then used in a comparative pharmacokinetics study with the market formulation in human volunteers. Results showed a marked change in MSP physicochemical properties of MSP-PLCP compared to MSP. Addition of mucoadhesive polymers to flushing resistant platform at an optimum concentration balanced between desired mucoadhesive properties and a reasonable drug release rate. The optimized formulation showed significantly a superior bioavailability in humans when compared to the market sublingual product. Finally, the novel developed sublingual flushing resistant platform offers a very promising and efficient tool to extend the use of sublingual route and widen its applications.

The present study deals with the formulation of topical insulin for wound healing with extended stability and sustained release, by applying quality by design concepts. Insulin has been promoted as a promising therapeutic wound healing agent. Topical formulation of insulin faced major problems, as it cannot be delivered safely to the wound with a controlled rate. Formulation of insulin-loaded vesicles in optimized bio-adhesive hydrogels has been explored to ensure a safe delivery of insulin to wounds in a controlled manner. Quality by design (QbD) was applied to study the effect of several critical process parameters on the critical quality attributes. Ishikawa diagram was used to identify the highest risk factors, which were screened by a fractional factorial design and augmented by Box–Behnken design. The optimized formula was incorporated into a mucoadhesive gel, which was further subjected to stability and clinical studies. An optimized formula was obtained with a particle size of 257.751 nm, zeta potential − 20.548 mv, 87.379% entrapment efficiency, and a release rate of 91.521 μg/cm2/h. The results showed that liposomal insulin remained stable for 6 months in aqueous dispersion state at 4°C. Moreover, the release was sustained up to 24 h. The clinical study showed an improvement in the wound healing rate, 16 times, as the control group, with magnificent reduction in the erythema of the ulcer and no signs of hypoglycemia. Insulin-loaded liposomal chitosan gel showed a promising drug delivery system with high stability and sustained release.

The application of minimally invasive surgical techniques in the field of orthopedic surgery has created a growing need for new injectable synthetic materials that can be used for bone grafting. In this work, novel injectable thermosensitive foam was developed by mixing nHAP powder with a thermosensitive polymer with foaming power (Pluronic F-127) and loaded with a water-soluble bisphosphonate drug (risedronate) to promote osteogenesis. The foam was able to retain the porous structure after injection and set through temperature change of PF-127 solution to form gel inside the body. The effect of different formulation parameters on the gelation time, porosity, foamability, injectability, and in vitro degradation in addition to drug release from the prepared foams were analyzed using a full factorial design. The addition of a co-polymer like methylcellulose or sodium alginate into the foam was also studied. Results showed that the prepared optimized thermosensitive foam was able to gel within 1 min at 37°C, and sustain the release of drug for 72 h. The optimized formulation was further tested for any interactions using DSC and IR, and revealed no interactions between the drug and the used excipients in the prepared foam. Furthermore, the ability of the pre-set foam to support osteoblastic-like Saos-2-cell proliferation and differentiation was assessed, and revealed superior function on promoting cellular proliferation as confirmed by fluorescence microscope compared to the plain drug solution. The activity of the foam treated cells was also assessed by measuring the alkaline phosphatase activity and calcium deposition, and confirmed that the cellular activity was greatly enhanced in foam treated cells compared to those treated with the plain drug solution only. The obtained results show that the prepared risedronate-loaded thermosensitive foam would represent a step forward in the design of new materials for minimally invasive bone regeneration.

Manganese, an essential nutrient for male reproductive health, exerts dose-dependent effects, with excessive exposure—particularly to manganese dioxide nanoparticles ( MnO 2 -NPs ) from environmental or industrial sources inducing gonadal damage via oxidative stress, hormonal disruption, and impaired steroidogenesis. This study evaluated rosemary essential oil ( REO ) against MnO 2 -NP -induced reproductive dysfunction in male rats. Seventy-two Sprague–Dawley rats (130 ± 10 g) were divided into six groups ( n  = 12): Group I (deionized water), Group II (saline), Group III ( MnO 2 -NP , 100 mg/kg bw/day), Group IV ( REO , 250 mg/kg/day), Protective Group V ( REO pre-treatment +  MnO 2 -NPs ), and Therapeutic Group VI ( MnO 2 -NPs + REO co-treatment) for 56 days. MnO 2 -NP exposure caused testicular injury, marked by elevated lipid peroxidation (↑malondialdehyde, ↑nitric oxide), suppressed antioxidants (↓total antioxidant capacity, ↓catalase, ↓glutathione), impaired sperm parameters (motility, count, morphology), and altered serum hormone levels (follicle-stimulating hormone, luteinizing hormone, testosterone). These effects correlated with downregulated steroidogenesis genes ( StAR , HSD-3β , CYP11A1 ). Both Protective and Therapeutic REO treatment mitigated MnO 2 -NPs oxidative stress, restored hormonal balance, and normalized gene expression. Histopathology revealed reduced seminiferous tubule degeneration and enhanced spermatogenesis in REO groups. Findings demonstrate REO’s efficacy in alleviating MnO 2 -NPs induced reproductive toxicity via antioxidant and steroidogenic modulation, positioning REO as a promising therapeutic against nanomaterial-induced gonadotoxicity.

Copper oxide nanoparticles (CuO-NPs) are known to trigger systemic toxicity through the disruption of copper homeostasis and the generation of profound oxidative stress. Given their widespread industrial applications, concerns persist regarding environmental and human exposure. This cascade of molecular injury drives multi-organ damage, immune suppression, and genomic instability. To address this concern, the present study systematically evaluates the potential of engineered curcumin nanoparticles (Cur-NPs) against CuO-NPs-induced toxicity in a rodent model as a proof of principle. Sixty adult male Sprague–Dawley rats were randomized into five experimental groups: control, vehicle (corn oil), CuO-NPs (50 mg/kg), Cur-NPs (50 mg/kg), and CuO-NPs + Cur-NPs co-treatment, administered orally for 30 days. Toxicological endpoints included oxidative stress biomarkers, immune functional assays (total leukocyte count, phagocytic index), regulation of apoptotic pathways (Bax/Bcl-2 ratio, caspase-3 activity), DNA integrity via the alkaline comet assay, and detailed histopathological examination of the liver, kidneys, and spleen. Exposure to CuO-NPs alone triggered severe oxidative damage, marked immunosuppression, a pro-apoptotic imbalance, and significant hepatic DNA fragmentation. Histopathology confirmed systemic injury, including hepatic necrosis, renal tubular degeneration, and splenic lymphoid depletion. Co-treatment with Cur-NPs significantly mitigated these effects, restoring antioxidant defences, immune competence, and apoptotic balance, while reducing DNA damage and tissue pathology. Cur-NPs alone maintained profiles comparable to controls, confirming their safety. Collectively, these findings reveal that Cur-NPs confer potent protection primarily by re-establishing redox homeostasis and modulating critical immune and apoptotic pathways, with copper chelation representing a proposed but unconfirmed contributory mechanism. This study provides a strong rationale for a plant-based, nanomaterial-enabled intervention to systemically protect against engineered nanomaterial toxicity in occupational settings, offering a foundation for developing exposure mitigation strategies. Highlights CuO-NPs provoke systemic toxicity: oxidative stress, immunosuppression, and DNA damage. Cur-NPs attenuate CuO-NPs-induced immunotoxicity, restoring leukocyte counts and phagocytic capacity. Cur-NPs protect against genomic instability, significantly reducing DNA damage. Cur-NPs restore apoptotic signalling equilibrium (Bax/Bcl-2 ratio) and ameliorate histopathological damage in the liver, kidneys, and spleen. Initial validation establishes nano-curcumin as a novel phytochemical for systemic protection in contexts relevant to workplace safety.

Manganese, an essential nutrient for male reproductive health, exerts dose-dependent effects, with excessive exposure-particularly to manganese dioxide nanoparticles (MnO -NPs) from environmental or industrial sources inducing gonadal damage via oxidative stress, hormonal disruption, and impaired steroidogenesis. This study evaluated rosemary essential oil (REO) against MnO -NP-induced reproductive dysfunction in male rats. Seventy-two Sprague-Dawley rats (130 ± 10 g) were divided into six groups (n = 12): Group I (deionized water), Group II (saline), Group III (MnO -NP, 100 mg/kg bw/day), Group IV (REO, 250 mg/kg/day), Protective Group V (REO pre-treatment + MnO -NPs), and Therapeutic Group VI (MnO -NPs + REO co-treatment) for 56 days. MnO -NP exposure caused testicular injury, marked by elevated lipid peroxidation (↑malondialdehyde, ↑nitric oxide), suppressed antioxidants (↓total antioxidant capacity, ↓catalase, ↓glutathione), impaired sperm parameters (motility, count, morphology), and altered serum hormone levels (follicle-stimulating hormone, luteinizing hormone, testosterone). These effects correlated with downregulated steroidogenesis genes (StAR, HSD-3β, CYP11A1). Both Protective and Therapeutic REO treatment mitigated MnO -NPs oxidative stress, restored hormonal balance, and normalized gene expression. Histopathology revealed reduced seminiferous tubule degeneration and enhanced spermatogenesis in REO groups. Findings demonstrate REO's efficacy in alleviating MnO -NPsinduced reproductive toxicity via antioxidant and steroidogenic modulation, positioning REO as a promising therapeutic against nanomaterial-induced gonadotoxicity.