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The hepatoprotective effect of β-Sitosterol (BSS), a natural phytosterol, after being formulated into a suitable pharmaceutical drug delivery system has not been widely explored. BSS was isolated from Centaurea pumilio L., identified and formulated as lipid-polymer hybrid nanoparticles (LPHNPs) using the poly(D,L-lactide-co-glycolide) polymer and DSPE-PEG-2000 lipid in different ratios. The selected formulation, prepared with a lipid: polymer: drug ratio of 2:2:2, had an entrapment efficiency (EE%) of 94.42 ± 3.8, particle size of 181.5 ± 11.3 nm, poly dispersity index (PDI) of 0.223 ± 0.06, zeta potential of −37.34 ± 3.21 and the highest drug release after 24 h. The hepatoprotective effect of the formulation at two different doses against CCl4 induced hepatotoxicity was evaluated in rats. The results showed that the BSS-LPHNPs (400 mg/kg) have the ability to restore the liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), liver lipid peroxidation markers (malondialdehyde (MDA) and catalase (CAT)), total bilirubin and albumin to their normal levels without inhibitory effect on the CYP2E1 activity. Also, the formulation could maintain the normal histological structure of liver tissue and decrease the cleaved caspase-3 expression. LPHNPs formulation encapsulating natural BSS is a promising hepatoprotective drug delivery system.

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Gallic acid (GA) is a naturally occurring compound with valuable antioxidant activity. Its oral bioavailability is limited by its high metabolism and rapid clearance. In this paper, GA was conjugated with two different materials, phosphatidylcholine (PC) and polyamidoamine (PAMAM) dendrimer. The prepared conjugates were characterized by FTIR, DSC, and SEM. Also, they were tested for drug content and in vitro drug release. It was found that GA conjugation with both materials have significantly prolonged its release up to 12 h. In vivo hepatoprotective activity of free and conjugated GA was studied in rats after carbon tetrachloride (CCl4)-induced oxidative damage in rat liver through measurement of different liver marker enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT)), in addition to the total protein and albumin level in rat serum. Also, histopathological examination of liver cell of all rat groups was done. Results showed that both prepared conjugates have significantly reduced the hepatic marker enzymes accompanied by normalizing total protein and albumin levels in rat serum and with respect to CCl4-induced group (p < .05). Histopathological examination showed that pretreatment of rats with GA-PC or GA-PAMAM before CCL4 could reduce the induced cellular histopathological changes. It appears that conjugation of GA could enhance its bioavailability and increase its hepatoprotective effect.

Enhancement of zolmitriptan bioavailability through development of micronized zolmitriptan pressurized metered dose inhaler (MDI) as an alternative to its traditional drug delivery systems. A reversed phase HPLC method for zolmitriptan determination was developed and evaluated. Micronized zolmitriptan MDI formulations were prepared using two different propellants. The prepared formulations were evaluated for mean shot weight, drug content, and leakage rate in addition to in-vitro deposition using next generation impactor where mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), fine particle dose, fine particle fraction (FPF), emitted dose (ED), and dispersibility were determined. The selected formulation was evaluated for in-vivo bronchial absorption in rats. The physicochemical characters of the prepared formulations were found to be dependent mainly on the vapor pressure of the used propellant. MDI formulation prepared with HFA 134a propellant was found to have the lowest MMAD (3.47 ± 0.65) with GSD of 2.3 ± 0.4. It also had the highest FPF (41.9), ED (89.26 ± 2.35) with dispersibility of 46.9%. This formulation, when applied to rats, resulted in faster T max (27 ± 5 min) with higher C max (1236 ± 116 ng/mL) and AUC (0-12) (3375 ± 482 ng/mL·h) over the oral tablet. Its relative bioavailability was 72.7% which was 1.25 times higher than the oral tablet relative bioavailability. Zolmitriptan MDI formulation was developed using micronized zolmitriptan powder without further modification or particle engineering. The developed formulation using HFA 134a propellant could be favorable alternative, with enhanced bioavailability, to zolmitriptan oral tablet for acute migraine treatment.