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This study investigated the development and characterization of leucine and magnesium stearate (MgSt) embedded wet milled inhalable ibuprofen (IBF) dry powder inhaler (DPI) formulations. IBF microparticles were prepared by a wet milling homogenization process and were characterized by SEM, FTIR, DSC, XRD and TGA. Using a Twin-Stage Impinger (TSI), the in vitro aerosolization of the formulations with and without carrier lactose was studied at a flow rate of 60± 5 L/min and the IBF was determined using a validated HPLC method. The flow properties were determined by the Carr’s Index (CI), Hausner Ratio (HR) and Angle of Repose (AR) of the milled IBF with 4–6.25% leucine and leucine containing formulations showed higher flow property than those of formulations without leucine. The fine particle fraction (FPF) of IBF from the prepared formulations was significantly (p = 0.000278) higher (37.1 ± 3.8%) compared to the original drug (FPF 3.7 ± 0.9%) owing to the presence of leucine, which enhanced the aerosolization of the milled IBF particles. Using quantitative phase analysis, the XPRD data revealed the crystallinity and accurate weight percentages of the milled IBF in the formulations. FTIR revealed no changes of the structural integrity of the milled IBF in presence of leucine or MgSt. The presence of 2.5% MgSt in the selected formulations produced the highest solubility (252.8 ± 0.6 µg/mL) of IBF compared to that of unmilled IBF (147.4 ± 1.6 µg/mL). The drug dissolution from all formulations containing 4–6.25% leucine showed 12.2–18.6% drug release in 2.5 min; however, 100% IBF dissolution occurred in 2 h whereas around 50% original and dry milled IBF dissolved in 2 h. The results indicated the successful preparation of inhalable IBF microparticles by the wet milling method and the developed DPI formulations with enhanced aerosolization and solubility due to the presence of leucine may be considered as future IBF formulations for inhalation.

This review focuses on the biomedical application of mesoporous silica nanoparticles (MSNs), mainly focusing on the therapeutic application of MSNs for cancer treatment and specifically on overcoming the challenges of currently available anthelmintics (e.g., low water solubility) as repurposed drugs for cancer treatment. MSNs, due to their promising features, such as tunable pore size and volume, ability to control the drug release, and ability to convert the crystalline state of drugs to an amorphous state, are appropriate carriers for drug delivery with the improved solubility of hydrophobic drugs. The biomedical applications of MSNs can be further improved by the development of MSN-based multimodal anticancer therapeutics (e.g., photosensitizer-, photothermal-, and chemotherapeutics-modified MSNs) and chemical modifications, such as poly ethyleneglycol (PEG)ylation. In this review, various applications of MSNs (photodynamic and sonodynamic therapies, chemotherapy, radiation therapy, gene therapy, immunotherapy) and, in particular, as the carrier of anthelmintics for cancer therapy have been discussed. Additionally, the issues related to the safety of these nanoparticles have been deeply discussed. According to the findings of this literature review, the applications of MSN nanosystems for cancer therapy are a promising approach to improving the efficacy of the diagnostic and chemotherapeutic agents. Moreover, the MSN systems seem to be an efficient strategy to further help to decrease treatment costs by reducing the drug dose.

The clinical utilization of fenbendazole (FBZ) as a potential anticancer drug has been limited due to its low water solubility, which causes its low bioavailability. The development of a drug nanoformulation that includes the solubilizing agent as a drug carrier can improve solubility and bioavailability. In this study, Mobil Composition of Matter Number 48 (MCM-48) nanoparticles were synthesized and functionalized with succinylated β-lactoglobulin (BLG) to prevent early-burst drug release. The BLG-modified amine-functionalized MCM-48 (MCM-BLG) nanoparticles were loaded with FBZ to produce the drug nanoformulation (FBZ-MCM-BLG) and improved the water solubility and, consequently, its anticancer effects against human prostate cancer PC-3 cells. The prepared FBZ-MCM-BLG was characterized in terms of size, zeta potential, drug loading capacity, morphology, thermal and chemical analyses, drug release, cellular uptake, cell viability, cell proliferation, production of reactive oxygen species (ROS), and cell migration. The results demonstrated that the FBZ-MCM-BLG nanoparticles have a spherical morphology with a size and zeta potential of 369 ± 28 nm and 28 ± 0.4 mV, respectively. The drug loading efficiency of the new nanoformulation was 19%. The release of FBZ was pH-dependent; a maximum cumulative release of about 76 and 62% in 12 h and a burst release of 53 and 38% in the first 0.5 h was observed at pH 1.2 and 6.8, respectively. The prepared FBZ-MCM-BLG formulation demonstrated higher cytotoxicity effects against PC-3 cells by 5.6- and 1.8-fold, respectively, when compared to FBZ and FBZ-MCM nanoparticles. The new formulation also increased the production of ROS by 1.6- and 1.2-fold and inhibited the migration of PC-3 cells when compared to the FBZ and FBZ-MCM nanoparticles, respectively. Overall, FBZ-MCM-BLG nanoparticles improved FBZ delivery to PC-3 cells and have the potential to be evaluated for the treatment of prostate cancer following a comprehensive in vivo study.

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.