Glyceryl behenate-based solid lipid nanoparticles as a carrier of haloperidol for nose to brain delivery: formulation development, in-vitro, and in-vivo evaluation

Abstract This study was aimed to develop the haloperidol (HPL) loaded solid lipid nanoparticles (SLNs) for brain targeting through the intranasal route. SLNs were fabricated by the emulsification diffusion technique using glyceryl behenate as lipid and tween 80 as a surfactant. SLNs were evaluated for particle size, zeta potential, structure, entrapment efficiency, solid state characterization by differential scanning calorimetry (DSC), and in-vitro release. In-vivo biological evaluation was performed on albino Wistar rats for the determination of pharmacokinetic as well as brain targeting parameters. Particle size, PDI, zeta potential, and entrapment efficiency of optimized formulation (HPL-SLNs 6) were found to be 103±09 nm, 0.190±0.029, -23.5±1.07 mV, and 79.46±1.97% respectively. In-vitro drug release studies exhibited that 87.21± 3.63% of the entrapped drug was released from the SLNs within 24 h. DSC curves confirmed that during entrapment in SLNs, the drug was solubilized in the lipid matrix and converted into the amorphous form. Enhanced HPL targeting to the brain was observed from HPL-SLNs as compared to HPL-Sol when administered intranasally. The value of AUC 0-∞ in the brain for HPL-SLNs i.n. was found to be nearly 2.7 times higher than that of HPL-Sol i.v., whereas 3.66 times superior to HPL-Sol administered i.n. Stability studies revealed that the formulation remains unchanged when stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months. Finally, it could be concluded that SLN is a suitable carrier for HPL with enhanced brain targeting through i.n administration, as compared to the HPL-Sol, administered i.n. and i.v.

Investigation of the potential anti-influenza activity of five plants grown in Sudan and used folklorically for respiratory infections

Respiratory tract infections caused by influenza viruses have challenged clinicians due to shortages of ideal antiviraltherapy or rapid development of resistance to available drugs. The development of new medications, especially fromnatural sources, is particularly important to combat the highly mutagenic influenza virus. This study was conducted totest the activity of some medicinal plants used traditionally in Sudan for the treatment of respiratory tract infectionsand other various diseases. Balanites aegyptiaca, Cordia africana, Aristolochia bracteolata, Boscia senegalensis, andLeptadenia arborea were extracted by water and methanol and tested against influenza virus strain A/WSN/33(H1N1)using zanamivir as a standard. The effective concentrations for methanol and water extracts were found in the rangesof 0.25–20 mg/ml and 10–35 mg/ml, respectively. The toxicities of all extracts were evaluated against Madin–Darbycanine kidney cells, and the cytotoxic concentration for all extracts was 80 mg/ml. Plants’ extracts at a concentrationof 2.5–20 mg/ml prevented hemagglutinin-assisted viral adsorption to RBCs using hemagglutination inhibitionassay. The proven anti-influenza activity of the tested plants could explain their folkloric use. It would be valuableto standardize the plants’ extracts and conduct in vivo studies so as to develop a safe and effective herbal formula forinfluenza.