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The biodistribution and pharmacokinetic characteristics of intravenously administered phenytoin sodium-loaded nanomicelles were assessed and compared to the commercially available phenytoin sodium iv at a dose of 25 mg/kg. In the biodistribution analysis, the phenytoin sodium-loaded nanomicelles displayed a maximum brain drug concentration of 865 ± 1.0 µg after 15 min of administration, whereas the marketed phenytoin sodium iv and phenytoin sodium solution exhibited maximum concentrations of 707.2 ± 65.6 µg and 168.4 ± 10.4 µg, respectively, after 30 min. Furthermore, in vivo biodistribution studies using dye-loaded polymeric nanomicelles demonstrated rapid brain uptake within five minutes of administration. During a 60-min period, the optimized formulation of nanomicelles resulted in higher plasma drug concentrations than the marketed formulation and phenytoin sodium solution, indicating reduced plasma protein binding. Additionally, the optimized nanomicelles exhibited lower drug deposition in peripheral organs when compared to the marketed phenytoin sodium iv, thereby reducing peripheral toxicity. Consequently, these findings suggest that phenytoin sodium-loaded nanomicelles hold promise as a potential treatment option for managing acute seizure emergencies. [ABSTRACT FROM AUTHOR]

Background: Doxorubicin-induced cardiotoxicity (DIC) is a major complication of cancer chemotherapy. Thus, developing effective myocardial protection strategies during doxorubicin (Dox) therapy is a medical necessity.Objectives: To evaluate and compare the cardioprotective effectiveness of free berberine (Ber) and berberine loaded in micelles (mBer) against DIC.Materials and Methods: The study, which was conducted in 2023, employed the H9c2 cell line, derived from embryonic cardiomyocytes, as a model. The study included a control group and six experimental groups: the Ber-treated group, the mBer-treated group, the Dox-treated group, the Ber-Dox combination-treated group, and the mBer-Dox combination-treated group, as well as the void micelles-treated group. The study evaluated the alterations in several cardiotoxicity markers with triplicate measurements: [lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB), and cardiac troponin I (cTn-1)], lipid peroxidation indicator (malondialdehyde (MDA), oxidative stress markers [Reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), inflammatory cytokines (interleukin-1β (IL-1β) and interleukin-6 (IL-6)], and the activity of the apoptosis proteins caspases 3/7. Results: The DOX group demonstrated significant increases in cardiotoxicity enzyme indices, lipid peroxidation, generation of free radicals, inflammatory cytokines, and caspase 3/7 activity relative to the control group. When Ber, or mBer, was co-delivered with Dox, the levels of LDH, CK-MB, cTn-1, and MDA significantly decreased. Whereas the activities of SOD and CAT were significantly improved when Ber, or mBer, was co-delivered with Dox. They reduced the elevation in both IL- β and IL-6 levels as well as the activities of caspases 3 and 7 induced by Dox. Importantly, the utilization of the micellar formulation of Ber in conjunction with Dox significantly enhanced the cardioprotective efficacy of Ber against DIC in H9c2 cells. Conclusion: Our results suggest that mBer offers a novel Ber delivery approach and prospective therapeutic strategy for the treatment of DIC.

Abstract Background Although a large amount of evidence has revealed that amyloid β (Aβ), especially Aβ oligomers, protofibrils, and pyroglutamated Aβs, participate primarily in the pathophysiological processes of Alzheimer’s disease, most clinical trials of anti-Aβ antibody therapy have never acquired successful efficacy in human clinical trials, partly because peripheral administration of antibody medications was unable to deliver sufficient amounts of the molecules to the brain. Recently, we developed polymeric nanomicelles capable of passing through the blood–brain barrier that function as chaperones to deliver larger amounts of heavy molecules to the brain. Herein, we aimed to evaluate the efficacy of newly developed antibody 6H4 fragments specific to Aβ oligomers encapsulated in polymeric nanomicelles on the development of Alzheimer’s disease pathology in Alzheimer’s disease model mice at the age of emergence of early Alzheimer’s disease pathology. Results During the 10-week administration of 6H4 antibody fragments in polymeric nanomicelles, a significant reduction in the amounts of various toxic Aβ species, such as Aβ oligomers, toxic Aβ conformers, and pyroglutamated Aβs in the brain was observed. In addition, immunohistochemistry indicated inhibition of diameters of Aβ plaques, Aβ-antibody immunoreactive areas, and also plaque core formation. Behavioral analysis of the mice model revealed that the 6H4 fragments-polymeric nanomicelle group was significantly better at maintaining long-term spatial reference memory in the probe and platform tests of the water maze, thereby indicating inhibition of the pathophysiological process of Alzheimer’s disease. Conclusions The results indicated that the strategy of reducing toxic Aβ species in early dementia owing to Alzheimer’s disease by providing sufficient antibodies in the brain may modify Alzheimer’s disease progression.

Background: Doxorubicin-induced cardiotoxicity (DIC) is a major complication of cancer chemotherapy. Thus, developing effective myocardial protection strategies during doxorubicin (Dox) therapy is a medical necessity. Objectives: To evaluate and compare the cardioprotective effectiveness of free berberine (Ber) and berberine loaded in micelles (mBer) against DIC. Materials and methods: The study, which was conducted in 2023, employed the H9c2 cell line, derived from embryonic cardiomyocytes, as a model. The study included a control group and six experimental groups: the Ber-treated group, the mBer-treated group, the Dox-treated group, the Ber-Dox combination-treated group, and the mBer-Dox combination-treated group, as well as the void micelles-treated group. The study evaluated the alterations in several cardiotoxicity markers with triplicate measurements: [lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB), and cardiac troponin I (cTn-1)], lipid peroxidation indicator (malondialdehyde (MDA), oxidative stress markers [Reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), inflammatory cytokines (interleukin-1β (IL-1β) and interleukin-6 (IL-6)], and the activity of the apoptosis proteins caspases 3/7. Results: The DOX group demonstrated significant increases in cardiotoxicity enzyme indices, lipid peroxidation, generation of free radicals, inflammatory cytokines, and caspase 3/7 activity relative to the control group. When Ber, or mBer, was co-delivered with Dox, the levels of LDH, CK-MB, cTn-1, and MDA significantly decreased. Whereas the activities of SOD and CAT were significantly improved when Ber, or mBer, was co-delivered with Dox. They reduced the elevation in both ILβ and IL-6 levels as well as the activities of caspases 3 and 7 induced by Dox. Importantly, the utilization of the micellar formulation of Ber in conjunction with Dox significantly enhanced the cardioprotective efficacy of Ber against DIC in H9c2 cells. Conclusion: Our results suggest that mBer offers a novel Ber delivery approach and prospective therapeutic strategy for the treatment of DIC. [ABSTRACT FROM AUTHOR]

Background: Although a large amount of evidence has revealed that amyloid β (Aβ), especially Aβ oligomers, protofibrils, and pyroglutamated Aβs, participate primarily in the pathophysiological processes of Alzheimer's disease, most clinical trials of anti-Aβ antibody therapy have never acquired successful efficacy in human clinical trials, partly because peripheral administration of antibody medications was unable to deliver sufficient amounts of the molecules to the brain. Recently, we developed polymeric nanomicelles capable of passing through the blood–brain barrier that function as chaperones to deliver larger amounts of heavy molecules to the brain. Herein, we aimed to evaluate the efficacy of newly developed antibody 6H4 fragments specific to Aβ oligomers encapsulated in polymeric nanomicelles on the development of Alzheimer's disease pathology in Alzheimer's disease model mice at the age of emergence of early Alzheimer's disease pathology. Results: During the 10-week administration of 6H4 antibody fragments in polymeric nanomicelles, a significant reduction in the amounts of various toxic Aβ species, such as Aβ oligomers, toxic Aβ conformers, and pyroglutamated Aβs in the brain was observed. In addition, immunohistochemistry indicated inhibition of diameters of Aβ plaques, Aβ-antibody immunoreactive areas, and also plaque core formation. Behavioral analysis of the mice model revealed that the 6H4 fragments-polymeric nanomicelle group was significantly better at maintaining long-term spatial reference memory in the probe and platform tests of the water maze, thereby indicating inhibition of the pathophysiological process of Alzheimer's disease. Conclusions: The results indicated that the strategy of reducing toxic Aβ species in early dementia owing to Alzheimer's disease by providing sufficient antibodies in the brain may modify Alzheimer's disease progression. [ABSTRACT FROM AUTHOR]

An acute seizure is a medical condition which, if untreated, can lead to brain damage and even death. Phenytoin sodium is a second-line drug of choice for seizure emergencies. Due to the administration issues as well as pharmacokinetic issues of the drug, it is now being replaced with newer anticonvulsant drugs despite short half life and sedative effects. This study aims to develop a polymeric nanomicelle of phenytoin sodium that decreases administration difficulties, enhances drug availability in the brain, and lowers the dose, all of which could be advantageous in the treatment of seizure emergencies. Phenytoin sodium–loaded polymeric nanomicelle was prepared by thin-film hydration method. A novel polymeric nanomicelle of size less than 20 nm loaded with phenytoin sodium was prepared with pluronic F127. Drug-loaded polymeric nanomicelle showed an immediate release profile with reduced PPB and improved lipid permeation when compared with the marketed iv injection of Phenytoin sodium. The in vivo acute toxicity study results revealed that the optimized formulation is safe for administration. The pharmacodynamic study by the MES model proved the enhanced brain availability as well as the reduced dose, thereby reducing peripheral toxicity. Results from the above studies confirm that the phenytoin sodium–loaded polymeric nanomicelle could potentially to be a better candidate for seizure emergencies, as it could reduce the administration issues, improve the brain availability of phenytoin, and lower the dose requirements. [ABSTRACT FROM AUTHOR]

Ciprofloxacin is a commonly prescribed antibiotic for treatment of pulmonary infections. Nanocarriers such as nanomicelles can increase the drug residence time in the lungs and enhance their antibacterial effects. Dry powder inhalers (DPIs) are the preferred pulmonary drug delivery system and preparation of an optimum nanoaggregate from nanomicelles by means of spray drying would be valuable. The two-level full factorial design was performed in 16 runs. The effects of carrier type, anti-adhesion agent type, carrier to nanoparticle ratio and anti-adhesion agent to carrier ratio on the size of the microparticles, their in vitro pulmonary deposition, and redispersibility were investigated. Its antibacterial effects against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Streptococcus pneumoniae also were investigated. All independent variables were fitted into two-factorial interaction models. The optimum nanoaggregate was prepared using mannitol and L-phenylalanine with a D0.5 of 1.7 µm and 60% fine particles. The process had no negative effect on the stability or drug release profile of the nanomicelles. The antibacterial effects of ciprofloxacin against microorganisms increased significantly. This spray drying process could be used for preparation of an optimum DPI from polymeric nanomicelles. This formulation could increase the efficacy of ciprofloxacin for treatment of pulmonary infections. [ABSTRACT FROM AUTHOR]