Background Parkinson's disease is a neurodegenerative disorder, and a major cause of disability. Levodopa, a prodrug of dopamine, remains the gold standard in the pharmacological management of Parkinson's disease. Despite several attempts to improve the clinical efficacy of levodopa, new oral levodopa formulations are needed to overcome irregular absorption and variable plasma concentrations. Objective The aim of this study was to evaluate the in vitro and in vivo kinetic properties of chitosan-coated hydroxypropylmethyl cellulose microparticles of levodopa (and carbidopa). Methods Microparticles were formulated by encapsulating levodopa powder in chitosan-coated hydroxypropylmethyl cellulose using the spray-drying method. Levodopa microparticles were evaluated for size, zeta potential, drug loading capacity, encapsulation efficiency and in vitro release. In evaluating in vivo pharmacokinetics, Sprague Dawley rats were administered either levodopa/carbidopa powder, levodopa/carbidopa microparticles, or Sinemet CR (a controlled release formulation of levodopa/carbidopa). The dose of respective formulations administered was 20/5 mg/kg; 20 mg levodopa combined with 5 mg carbidopa per kilogram body weight of animals. Treatments were administered via the oral route every 12 hours. Blood samples were collected after predetermined times following the third dose. Plasma was obtained from blood collected, and levodopa levels determined by HPLC. Pharmacokinetic parameters, including C max , T max , AUC, and t ½ of the various formulations, were estimated. Results The mean (SD) size of levodopa microparticles was 0.5 (0.05) µm with polydispersity index of 0.41 and a zeta potential of 10.8 mV. Of the expected 20% drug loading, the actual drug loading capacity of levodopa microparticles was found to be 19.1%, giving an encapsulation efficiency of 95.7%. The in vitro release kinetics of levodopa microparticles showed a controlled and sustained release, with about 80% release occurring after 12 hours. In vivo pharmacokinetic studies showed that rats administered levodopa/carbidopa microparticles had greater AUC (612.7 [17.42] ng.h/mL) and higher C max (262.4 [38.86] ng/mL) compared with Sinemet CR: AUC 354.7 (98.09) ng.h/mL and C max 95.5 (20.87) ng/mL. However, Sinemet CR had a much longer half-life (6.1 [2.58] hours) compared with levodopa/carbidopa microparticles (2.0 [0.31] hours). Conclusions Findings from this study suggest that chitosan-coated hydroxypropylmethyl cellulose microparticles of levodopa/carbidopa may give relatively high levels of levodopa in circulation. ( Curr Ther Res Clin Exp. 2020; 81:XXX–XXX) © 2020 Elsevier HS Journals, Inc.

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Due to the fact that coronavirus disease 2019 (COVID-19) is still prevalent, and current reports show that some parts of the world have seen increase in incidence, it is relevant that health professionals and scientists know about recent or novel trends, especially drug treatments. Additionally, the safety profiles of these drug treatments need to be documented and shared with the public. Some studies have demonstrated the clinical benefits of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in COVID-19 treatment. On the contrary, others have also reported that NSAIDs and corticosteroids may worsen symptoms associated with COVID-19. While some researchers have suggested that corticosteroids may be helpful if used in the early stages of COVID-19, there are still some conflicting findings regarding the use of corticosteroids in certain viral infections. Our review suggests that methylprednisolone, dexamethasone, and ibuprofen have therapeutic potential in reducing mortality due to COVID-19 among hospitalized patients. This review also highlights the fact that the use of NSAIDs is not associated with adverse outcomes of COVID-19. In reality, evidence suggests that NSAIDs do not increase the risk of COVID-19 infections. Also, the literature reviewed suggests that corticosteroid treatment in COVID-19 was linked with a decrease in all-cause mortality and disease progression, without increase in adverse events when compared to no corticosteroid treatment.

Background: Diabetic cardiomyopathy (DCM) is a major long-term complication of diabetes mellitus, accounting for over 20% of annual mortality rate of diabetic patients globally. Although several existing anti-diabetic drugs have improved glycemic status in diabetic patients, prevalence of DCM is still high. This study investigates cardiac effect of alpha-lipoic acid (ALA) supplementation of anti-diabetic therapy in experimental DCM.Methods: Following 12 h of overnight fasting, 44 male Sprague Dawley rats were randomly assigned to two groups of healthy control (n = 7) and diabetic (n = 37) groups, and fasting blood glucose was measured. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by intraperitoneal (i.p.) administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). After confirmation of T2DM on day 3, diabetic rats received monotherapies with ALA (60 mg/kg; n = 7), gliclazide (15 mg/kg; n = 7), ramipril (10 mg/kg; n = 7) or combination of the three drugs (n = 7) for 6 weeks while untreated diabetic rats received distilled water and were used as diabetic control (n = 9). Rats were then sacrificed, and blood, pancreas and heart tissues were harvested for analyses using standard methods.Results: T2DM induction caused pancreatic islet destruction, hyperglycemia, weight loss, high relative heart weight, and development of DCM, which was characterized by myocardial degeneration and vacuolation, cardiac fibrosis, elevated cardiac damage markers (plasma and cardiac creatine kinase-myocardial band, brain natriuretic peptide and cardiac troponin I). Triple combination therapy of ALA, gliclazide and ramipril preserved islet structure, maintained body weight and blood glucose level, and prevented DCM development compared to diabetic control (p < 0.001). In addition, the combination therapy markedly reduced plasma levels of inflammatory markers (IL-1β, IL-6 and TNF-α), plasma and cardiac tissue malondialdehyde, triglycerides and total cholesterol while significantly increasing cardiac glutathione and superoxide dismutase activity and high-density lipoprotein-cholesterol compared to diabetic control (p < 0.001). Mechanistically, induction of T2DM upregulated cardiac expression of TGF-β1, phosphorylated Smad2 and Smad3 proteins, which were downregulated following triple combination therapy (p < 0.001).Conclusion: Triple combination therapy of ALA, gliclazide and ramipril prevented DCM development by inhibiting TGF-β1/Smad pathway. Our findings can be extrapolated to the human heart, which would provide effective additional pharmacological therapy against DCM in T2DM patients.