Rofecoxib (ROF), a potent selective COX-II inhibitor NSAID, has been withdrawn from the market due to its high risk on patients with cardiovascular disorders (CVD). In the current study, an attempted to re-introduce ROF into the market via co-formulation with the antiplatelet drug, Aspirin, to neutralize ROF effect on the platelet function has been investigated. Solubility and dissolution profiles of ROF were studied and improved through formulation into solid dispersions with Soluplus® before being mixed with a low dose of Aspirin. The novel drug combination was incorporated into oral tablets with various compositions to optimize the tablets physico-chemical performance. In addition, a new validated HPLC method was developed for simultaneous assessment of both drugs in the tablets. The optimized tablets demonstrated satisfactory physico-chemical performance. The developed HPLC method was accurate, precise, robust and sensitive with limits of detection (LODs) of 2.96 and 0.25 μg/mL and limits of quantitation (LOQs) of 8.77 and 0.77 μg/mL for Aspirin and ROF, respectively. The novel co-therapy showed normal platelet function in rabbits in opposite to ROF monothrapy. The data presented in this study can be promising to re-utilize ROF as an effective and selective NSAID, to satisfy the market's demand, while ensuring its safety in CVD patients.

Rofecoxib (ROF), a potent selective COX-II inhibitor NSAID, has been withdrawn from the market due to its high risk on patients with cardiovascular disorders (CVD). In the current study, an attempted to re-introduce ROF into the market via co-formulation with the antiplatelet drug, Aspirin, to neutralize ROF effect on the platelet function has been investigated. Solubility and dissolution profiles of ROF were studied and improved through formulation into solid dispersions with Soluplus® before being mixed with a low dose of Aspirin. The novel drug combination was incorporated into oral tablets with various compositions to optimize the tablets physico-chemical performance. In addition, a new validated HPLC method was developed for simultaneous assessment of both drugs in the tablets. The optimized tablets demonstrated satisfactory physico-chemical performance. The developed HPLC method was accurate, precise, robust and sensitive with limits of detection (LODs) of 2.96 and 0.25 μg/mL and limits of quantitation (LOQs) of 8.77 and 0.77 μg/mL for Aspirin and ROF, respectively. The novel co-therapy showed normal platelet function in rabbits in opposite to ROF monothrapy. The data presented in this study can be promising to re-utilize ROF as an effective and selective NSAID, to satisfy the market's demand, while ensuring its safety in CVD patients.

Rofecoxib (ROF), a potent selective COX-II inhibitor NSAID, has been withdrawn from the market due to its high risk on patients with cardiovascular disorders (CVD). In the current study, an attempted to re-introduce ROF into the market via co-formulation with the antiplatelet drug, Aspirin, to neutralize ROF effect on the platelet function has been investigated. Solubility and dissolution profiles of ROF were studied and improved through formulation into solid dispersions with Soluplus® before being mixed with a low dose of Aspirin. The novel drug combination was incorporated into oral tablets with various compositions to optimize the tablets physico-chemical performance. In addition, a new validated HPLC method was developed for simultaneous assessment of both drugs in the tablets. The optimized tablets demonstrated satisfactory physico-chemical performance. The developed HPLC method was accurate, precise, robust and sensitive with limits of detection (LODs) of 2.96 and 0.25 μg/mL and limits of quantitation (LOQs) of 8.77 and 0.77 μg/mL for Aspirin and ROF, respectively. The novel co-therapy showed normal platelet function in rabbits in opposite to ROF monothrapy. The data presented in this study can be promising to re-utilize ROF as an effective and selective NSAID, to satisfy the market's demand, while ensuring its safety in CVD patients.

Rofecoxib (ROF), a potent selective COX-II inhibitor NSAID, has been withdrawn from the market due to its high risk on patients with cardiovascular disorders (CVD). In the current study, an attempted to re-introduce ROF into the market via co-formulation with the antiplatelet drug, Aspirin, to neutralize ROF effect on the platelet function has been investigated. Solubility and dissolution profiles of ROF were studied and improved through formulation into solid dispersions with Soluplus® before being mixed with a low dose of Aspirin. The novel drug combination was incorporated into oral tablets with various compositions to optimize the tablets physico-chemical performance. In addition, a new validated HPLC method was developed for simultaneous assessment of both drugs in the tablets. The optimized tablets demonstrated satisfactory physico-chemical performance. The developed HPLC method was accurate, precise, robust and sensitive with limits of detection (LODs) of 2.96 and 0.25 μg/mL and limits of quantitation (LOQs) of 8.77 and 0.77 μg/mL for Aspirin and ROF, respectively. The novel co-therapy showed normal platelet function in rabbits in opposite to ROF monothrapy. The data presented in this study can be promising to re-utilize ROF as an effective and selective NSAID, to satisfy the market's demand, while ensuring its safety in CVD patients.

Sulpiride (SUL), anti-dopaminergic drug, has a specific site for absorption located in the upper portion of the gastrointestinal tract hence, its oral delivery represents a challenge regarding SUL absorption and bioavailability. So, a gastro-retentive oral platform of SUL was developed to increase its gastric residence time, release SUL at a controlled rate in the stomach and consequently, enable it to reach its specific absorption site. Floating microsponges were prepared via quasi-emulsion solvent diffusion method and characterised for their physico-chemical properties. In addition, Taguchi design of experiment was utilised to optimise some independent variables affecting microsponges performance. The optimised SUL microsponges showed a yield of 79.82 ± 2.37%, an encapsulation efficiency of 89.11 ± 2.28% and in vitro time for floatation of 8.0 h. Additionally, pharmacokinetics were investigated in rabbits and compared with the commercial SUL formulation, Dogmatil® capsules. Optimised SUL microsponges showed a significantly (p  .05) higher Cmax, AUC and 2-fold increase in oral bioavailability compared with the commercial product. Moreover, the optimised SUL microsponges remained present in the stomach up to 8.0 h post administration when viewed via X-ray radiographs in rabbits. It could be concluded that the floating microsponges could be useful as an oral platform to enhance the sulpiride absorption and bioavailability.

Sulpiride (SUL), anti-dopaminergic drug, has a specific site for absorption located in the upper portion of the gastrointestinal tract hence, its oral delivery represents a challenge regarding SUL absorption and bioavailability. So, a gastro-retentive oral platform of SUL was developed to increase its gastric residence time, release SUL at a controlled rate in the stomach and consequently, enable it to reach its specific absorption site. Floating microsponges were prepared via quasi-emulsion solvent diffusion method and characterised for their physico-chemical properties. In addition, Taguchi design of experiment was utilised to optimise some independent variables affecting microsponges performance. The optimised SUL microsponges showed a yield of 79.82 ± 2.37%, an encapsulation efficiency of 89.11 ± 2.28% and in vitro time for floatation of 8.0 h. Additionally, pharmacokinetics were investigated in rabbits and compared with the commercial SUL formulation, Dogmatil® capsules. Optimised SUL microsponges showed a significantly (p  .05) higher Cmax, AUC and 2-fold increase in oral bioavailability compared with the commercial product. Moreover, the optimised SUL microsponges remained present in the stomach up to 8.0 h post administration when viewed via X-ray radiographs in rabbits. It could be concluded that the floating microsponges could be useful as an oral platform to enhance the sulpiride absorption and bioavailability.

Sulpiride (SUL), anti-dopaminergic drug, has a specific site for absorption located in the upper portion of the gastrointestinal tract hence, its oral delivery represents a challenge regarding SUL absorption and bioavailability. So, a gastro-retentive oral platform of SUL was developed to increase its gastric residence time, release SUL at a controlled rate in the stomach and consequently, enable it to reach its specific absorption site. Floating microsponges were prepared via quasi-emulsion solvent diffusion method and characterised for their physico-chemical properties. In addition, Taguchi design of experiment was utilised to optimise some independent variables affecting microsponges performance. The optimised SUL microsponges showed a yield of 79.82 ± 2.37%, an encapsulation efficiency of 89.11 ± 2.28% and in vitro time for floatation of 8.0 h. Additionally, pharmacokinetics were investigated in rabbits and compared with the commercial SUL formulation, Dogmatil® capsules. Optimised SUL microsponges showed a significantly (p  .05) higher Cmax, AUC and 2-fold increase in oral bioavailability compared with the commercial product. Moreover, the optimised SUL microsponges remained present in the stomach up to 8.0 h post administration when viewed via X-ray radiographs in rabbits. It could be concluded that the floating microsponges could be useful as an oral platform to enhance the sulpiride absorption and bioavailability.

Treatment for hepatocellular carcinoma (HCC) is currently limited to early stages where surgical intervention is applicable. Meanwhile, the response for most chemotherapies is still low, leaving patients in advanced stages without an effective therapeutic approach. Other therapeutic strategies based on immunotherapies or radiotherapy have a narrow spectrum with multiple limitations. These collective drawbacks necessitate the development of alternative strategies. Gene therapy has achieved a breakthrough in the treatment of several diseases, especially tumors. In the current review, a discussion is provided on the various strategies that have been developed for HCC gene therapy, the functional and genetic materials used, and their diverse delivery systems, with a special focus on novel targeting strategies based on biomaterials, peptide libraries, and aptamers. In addition, animal models that have been used in preclinical evaluation of HCC gene therapies are highlighted and compared. Lastly, ongoing clinical trials and future perspectives for these strategies are discussed.

Treatment for hepatocellular carcinoma (HCC) is currently limited to early stages where surgical intervention is applicable. Meanwhile, the response for most chemotherapies is still low, leaving patients in advanced stages without an effective therapeutic approach. Other therapeutic strategies based on immunotherapies or radiotherapy have a narrow spectrum with multiple limitations. These collective drawbacks necessitate the development of alternative strategies. Gene therapy has achieved a breakthrough in the treatment of several diseases, especially tumors. In the current review, a discussion is provided on the various strategies that have been developed for HCC gene therapy, the functional and genetic materials used, and their diverse delivery systems, with a special focus on novel targeting strategies based on biomaterials, peptide libraries, and aptamers. In addition, animal models that have been used in preclinical evaluation of HCC gene therapies are highlighted and compared. Lastly, ongoing clinical trials and future perspectives for these strategies are discussed.

Hepatocellular carcinoma (HCC) is a fatal disease with limited therapeutic choices. The stroma-rich tumor microenvironment hinders the in vivo delivery of most nanomedicines. Ultra-small lipid nanoparticles (usLNPs) were designed for the selective co-delivery of the cytotoxic drug, sorafenib (SOR), and siRNA against the Midkine gene (MK-siRNA) to HCC in mice. The usLNPs composed of a novel pH-sensitive lipid, a diversity of phospholipids and a highly-selective targeting peptide. A microfluidic device, iLiNP, was used and a variety of factors were controlled to tune particle size aiming at maximizing tumor penetration efficiency. Optimizing the composition and physico-chemical properties of the usLNPs resulted in an enhanced tumor accumulation, selectivity and in vivo gene silencing. The optimized usLNPs exerted potent gene silencing in the tumor (median effective dose, ED50~0.1 mg/Kg) with limited effect on the healthy liver. The novel combination synergistically-eradicated HCC in mice (~85%) at a surprisingly-low dose of SOR (2.5 mg/Kg) which could not be achieved via individual monotherapy. Toxicity studies revealed the biosafety of the usLNPs upon either acute or chronic treatment. Furthermore, the SOR-resistant HCC established in mice was eradicated by 70% using this approach. We conclude that our strategy is promising for potential clinical applications in HCC treatment.