The last few years have witnessed a great advance in the development of nonviral systems for in vivo targeted delivery of nucleic acids. Lipid nanoparticles (LNPs) are the most promising carriers for producing clinically approved products in the future. Compared with other systems used for nonviral gene delivery, LNPs provide several advantages including higher stability, low toxicity, and greater efficiency. Additionally, systems based on LNPs can be modified with ligands and devices for controlled biodistribution and internalization into specific cells. Efforts are ongoing to improve the efficiency of lipid-based gene vectors. These efforts depend on the appropriate design of nanocarriers as well as the development of new lipids with improved gene delivery ability. Several ionizable lipids have recently been developed and have shown dramatically improved efficiency. However, enhancing the ability of nanocarriers to target specific cells in the body remains the most difficult challenge. Systemically administered LNPs can access organs in which the capillaries are characterized by the presence of fenestrations, such as the liver and spleen. The liver has received the most attention to date, although targeted delivery to the spleen has recently emerged as a promising tool for modulating the immune system. In this review, we discuss recent advances in the use of LNPs for cell-specific targeted delivery of nucleic acids. We focus mainly on targeting liver hepatocytes and spleen immune cells as excellent targets for gene therapy. We also discuss the potential of endothelial cells as an alternate approach for targeting organs with a continuous endothelium.

The last few years have witnessed a great advance in the development of nonviral systems for in vivo targeted delivery of nucleic acids. Lipid nanoparticles (LNPs) are the most promising carriers for producing clinically approved products in the future. Compared with other systems used for nonviral gene delivery, LNPs provide several advantages including higher stability, low toxicity, and greater efficiency. Additionally, systems based on LNPs can be modified with ligands and devices for controlled biodistribution and internalization into specific cells. Efforts are ongoing to improve the efficiency of lipid-based gene vectors. These efforts depend on the appropriate design of nanocarriers as well as the development of new lipids with improved gene delivery ability. Several ionizable lipids have recently been developed and have shown dramatically improved efficiency. However, enhancing the ability of nanocarriers to target specific cells in the body remains the most difficult challenge. Systemically administered LNPs can access organs in which the capillaries are characterized by the presence of fenestrations, such as the liver and spleen. The liver has received the most attention to date, although targeted delivery to the spleen has recently emerged as a promising tool for modulating the immune system. In this review, we discuss recent advances in the use of LNPs for cell-specific targeted delivery of nucleic acids. We focus mainly on targeting liver hepatocytes and spleen immune cells as excellent targets for gene therapy. We also discuss the potential of endothelial cells as an alternate approach for targeting organs with a continuous endothelium.

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.

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.