Antibody Conjugated Nano-Enabled Drug Delivery Systems Against Brain Tumors.

The use of antibody-conjugated nanoparticles for brain tumor treatment has gained significant attention in recent years. Nanoparticles functionalized with anti-transferrin receptor antibodies have shown promising results in facilitating nanoparticle uptake by endothelial cells of brain capillaries and post-capillary venules. This approach offers a potential alternative to the direct conjugation of biologics to antibodies. Furthermore, studies have demonstrated the potential of antibody-conjugated nanoparticles in targeting brain tumors, as evidenced by the specific binding of these nanoparticles to brain cancer cells. Additionally, the development of targeted nanoparticles designed to transcytoses the blood-brain barrier (BBB) to deliver small molecule drugs and therapeutic antibodies to brain metastases holds promise for brain tumor treatment. While the use of nanoparticles as a delivery method for brain cancer treatment has faced challenges, including the successful delivery of nanoparticles to malignant brain tumors due to the presence of the BBB and infiltrating cancer cells in the normal brain, recent advancements in nanoparticle-mediated drug delivery systems have shown potential for enhancing the efficacy of brain cancer therapy. Moreover, the development of brain-penetrating nanoparticles capable of distributing over clinically relevant volumes when administered via convection-enhanced delivery presents a promising strategy for improving drug delivery to brain tumors. In conclusion, the use of antibody-conjugated nanoparticles for brain tumor treatment shows great promise in overcoming the challenges associated with drug delivery to the brain. By leveraging the specific targeting capabilities of these nanoparticles, researchers are making significant strides in developing effective and targeted therapies for brain tumors.

Nanoparticle-containing lyophilized dry powder inhaler formulations optimized using central composite design with improved aerodynamic parameters and redispersibility.

Objectives: The aim of this study was to improve the aerodynamic behavior and redispersibility of a lyophilized dry powder inhaler (DPI) formulation containing nanoparticles.Methods: Paclitaxel (PTX)-human serum albumin (HSA) nanoparticles were used as a model, and DPIs containing the nanoparticles were produced by lyophilization using different carriers and carrier ratios. A central composite design was employed to optimize the formulation. L-leucine and mannitol were chosen as independent variables, and mass median aerodynamic diameter (MMAD), emitted fraction, fine particle fraction (FPF), nanoparticle size, polydispersity index (PDI), zeta potential were selected as dependent variables.Results: The water content of DPIs was less than 5% for all DPIs. The cytotoxicity of the DPIs, determined using A549 cells, was due to PTX alone. Particle sizes of 204.3 ± 1.65 nm and 94.3-1353.0 nm were obtained before and after lyophilization, respectively. The developed method resulted in a reduction in the MMAD from 8.148 µm to 5.274 µm, an increase in the FPF from 17.63% to 33.60%, and an increase in the emitted fraction from 77.68% to 97.03%. The physico-chemical characteristics of the optimized formulation were also assessed.Conclusions: In conclusion, this study demonstrates that lyophilization can be used to produce nanoparticle-containing DPI formulations with improved redispersibility and aerodynamic properties.

Development and characterization of metformin hydrochloride- and glyburide-containing orally disintegrating tablets.

Diabetes is characterized by chronic hyperglycemia. Although metformin hydrochloride (MHCl)- and glyburide (GLB)-containing conventional tablets are available in the market and used to treat diabetes, orally disintegrating tablets (ODTs) containing the combination of these drugs are not commercially available. Therefore, the aim of this study was to prepare ODTs containing MHCl and GLB by direct-compression (DC-ODTs) and freeze-drying (FD-ODTs) methods. Physical properties of the powder mixture of DC-ODT formulation were determined (Angle of repose: 37.18 ± 1.27°; compressibility index: 20.31 ± 1.06%; Hausner ratio: 1.25 ± 0.03). Its moisture content was 0.3 ± 0.09%. The hardness values and the disintegration times for DC-ODTs and FD-ODTs were 221.60 ± 40.82 and 66.54 ± 2.68 N, and 80 and 30 s, respectively. Friability values were 0.24% for DC-ODTs and 0.38% for FD-ODTs. In uniformity-of-mass for single-dose-preparations test, the average weight was 684.38 ± 1.97 mg for DC-ODTs and 342.93 ± 2.4 mg for FD-ODTs, with less than 5% deviation for all 20 tablets. Water-absorption ratio for DC-ODTs was 1.30 ± 0.05. More than 90% of MHCl and GLB were dissolved within 5 min in both DC-ODTs and FD-ODTs. Although Caco-2 permeability of MHCl was influenced by the ODTs, GLB permeability was not. These results indicated that MHCl- and GLB-containing ODTs may be used as promising formulations for the treatment of diabetes.

Development of an Anti-Inflammatory Drug-Incorporated Biomimetic Scaffold for Corneal Tissue Engineering.

Purpose: The aim of this study was to design naproxen sodium (NS)-containing, biomimetic, porous poly(lactide-co-glycolide) (PLGA) scaffolds for regeneration of damaged corneal epithelium. Methods: NS-incorporated PLGA scaffolds were prepared using the emulsion freeze-drying method and then coated with collagen or poly-l-lysine. Porosity measurements of the scaffolds were performed by the gas adsorption/desorption method and the scaffolds demonstrated highly porous, open-cellular pore structures with pore sizes from 150 to 200 µm. Results: The drug loading efficiency of scaffolds was found to be higher than 84%, and about 90%-98% of NS was released at the end of 7 days with a fast drug release rate at the initial period of time and then in a slow and sustained manner. The corneal epithelial cells were isolated from New Zealand white rabbits. The obtained cells were seeded onto scaffolds and continued to increase during the time period of the study, indicating that the scaffolds might promote corneal epithelial cell proliferation without causing toxic effects for at least 10 days. Conclusions: The NS-loaded PLGA scaffolds exhibited a combination of controlled drug release and biomimetic properties that might be attractive for use in treatment of corneal damage both for controlled release and biomedical applications.

Cyber-physical-based PAT (CPbPAT) framework for Pharma 4.0.

Industry 4.0 aims to integrate manufacturing operations into a seamless digital whole by incorporating flexibility, agility, re-configurability, and sustainability. The result of this integration is a "smart factory" that is more lean, agile, and flexible in operations. There are valid reasons, and perhaps requirements, for pharmaceutical industries to embrace smart factory and to "borrow" the concept of Industry 4.0 to give rise to "Pharma 4.0" (i.e., the pharmaceutical version of Industry 4.0). This paper proposes a cyber-physical-based PAT framework called CPbPAT for implementing smart manufacturing systems in the pharmaceutical industry. The framework has been developed using an agent-based system and is presented by a standard system modeling language called the Unified Modeling Language (UML). The pharmaceutical manufacturing system shown in "Quality by Design for ANDAs" is used as a case study to illustrate the application of the proposed framework.