RESUMO
Resistance to isoniazid (INH) is common and increases the possibility of acquiring multidrug-resistant tuberculosis. For this study, isoniazid-loaded nanostructured lipid carriers (INH-NLCs) were developed and effectively functionalized with mannose (Man) to enhance the residence time of the drug within the lungs via specific delivery and increase the therapeutic efficacy of the formulation. The mannose-functionalized isoniazid-loaded nanostructured lipid carrier (Man-INH-NLC) formulation was evaluated with respect to various formulation parameters, namely, encapsulation efficiency (EE), drug loading (DL), average particle size (PS), zeta potential (ZP), polydispersity index (PDI), in vitro drug release (DR), and release kinetics. The in vitro inhalation behavior of the developed formulation after nebulization was investigated using an Andersen cascade impactor via the estimation of the mass median aerosolized diameter (MMAD) and geometric aerodynamic diameter (GAD) and subsequently found to be suitable for effective lung delivery. An in vivo pharmacokinetic study was carried out in a guinea pig animal model, and it was demonstrated that Man-INH-NLC has a longer residence time in the lungs with improved pharmacokinetics when compared with unfunctionalized INH-NLC, indicating the enhanced therapeutic efficacy of the Man-INH-NLC formulation. Histopathological analysis led us to determine that the extent of tissue damage was more severe in the case of the pure drug solution of isoniazid compared to the Man-INH-NLC formulation after nebulization. Thus, the nebulization of Man-INH-NLC was found to be safe, forming a sound basis for enhancing the therapeutic efficacy of the drug for improved management in the treatment of pulmonary tuberculosis.
RESUMO
The current study was planned to investigate the pharmacological basis of Solanum virginianum extract (SV.CR) pertaining to anxiolytic, antidepressant and memory-enhancing effects in rats. The SV.CR was analyzed in-vitro for phytoconstituents, antioxidant potential and anticholinesterase activity. The rats treated in a dose-dependent manner (25, 50 and 100 mg/kg of SV.CR) were subjected to behavioral tests for anxiety, depression and memory judgment followed by biochemical studies. A notable dose-dependent anxiolytic potential of SV.CR was observed in elevated plus maze and open field tests (P < 0.05). The decreased immobility time of the treated rats in the forced swim test (P < 0.01) unveiled the plant's potential to reduce depression. Moreover, SV.CR treatment also reversed scopolamine-impaired cognition (P < 0.05) in various deployed memory and learning tasks. Biochemical studies of brain homogenates of SV.CR treated animals demonstrated decreased anticholinesterase activity and lipid peroxidation levels whereas increased levels of superoxide dismutase and glutathione peroxidase (P < 0.05 vs scopolamine group) were noted. The scientific validation of the study supported the use of Solanum virginianum in reducing anxiety, depression and amnesia in experimental models. Phytoconstituents in SV.CR such as oleanolic acid and caffeic acid might have played a significant neuroprotective role via modulation of oxidative stress and neurochemical aspects.
RESUMO
The essential oil of Meriandra dianthera (Konig ex Roxb.) Benth. (Synonym: Meriandra bengalensis, Lamiaceae) collected from Saudi Arabia was studied utilizing GC and GC/MS. Forty four constituents were identified, representing 96.8% of the total oil. The M. dianthera essential oil (MDEO) was characterized by a high content of oxygenated monoterpenes (76.2%). Camphor (54.3%) was the major compound in MDEO followed by 1,8-cineole (12.2%) and camphene (10.4%). Moreover, MDEO was assessed for its cytotoxic, antimicrobial, and antioxidant activities. MDEO demonstrated an interesting cytotoxic activity against all cancer cell lines with IC50 values of 83.6 to 91.2 µg/mL, especially against MCF-7 cancer cells. Using labeling with annexin VFITC and/or propidium iodide (PI) dyes and flow cytometer analysis, the apoptosis induction was quantitatively confirmed for MCF-7 cells. The MDEO exhibited a considerable antimicrobial activity against all bacterial and fungal strains with minimum inhibitory concentration (MIC)-values of 0.07 to 1.25 mg/mL. The most sensitive microbial strain was Staphylococcus aureus (MIC: 0.07 mg/mL). Minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) values were determined one time higher than that of MIC's. Additionally, the MDEO revealed a strong activity for reducing ß-carotene bleaching with a total antioxidant value of 72.6% and significant DPPH free radical scavenging activity (78.4%) at the concentration 1000 µg/mL.