European Journal of Molecular & Clinical Medicine

Background:Ulcerative colitis (UC) is a chronic inflammatory disease of large intestine.
Overproduction of free radicals, lowered antioxidant capacity, inflammation and
abnormal apoptosis are involved in its pathogenesis. Propranolol and carvedilol, β-
blockers with antioxidant and anti-inflammatory effects which may have a protective role
in UC.
The study aimed to evaluate and compare the effects of propranolol and carvedilol on UC
development and to distinguish which of them have greater beneficial effect on
experimentally-induced UC in male albino rats.
Methods: Fifty male albino rats were randomly allocated to five groups with each group
comprising eleven rats except control group composed of six rats. Group (1): control
group, Group (2): ulcerative colitis group, Group (3): propranolol-pretreated (30
mg/kg/d), Group (4): carvedilol-pretreated (30 mg/kg/d) and Group (5): mesalazinepretreated
(300 mg/kg/d). Treated groups received drugs by oral gavage for seven days
before and three days after induction of colitis. UC was induced in groups 2 to 5 by
intrarectal administration of 1ml of 4% Acetic Acid (AA), while group (1)received 1 ml of
normal saline solution administered intrarectally instead. To estimate the severity of AAinduced
UC and the effect of propranolol and carvedilol, the following parameters were
measured: colon weight/length (W/L) ratio, colon weight/body weight (CW/BW) ratio,
colonic malondialdehyde (MDA) and colonic markers of inflammation [tumor necrosis
factor (TNF-α) and nuclear factor kappa B (NF-κB)] and macroscopic and microscopic
scorings.
Results:In UC group, colon W/L ratio, CW/BW ratio, macroscopic and microscopic
scorings and colonic levels of MDA, TNF-α and NF-κBwere significantly increased.
Pretreatment with propranolol, carvedilol and mesalazine significantly reduced these
parameters when compared to UC group. However, colon W/L ratio, CW/BW ratio,
macroscopic scoring of mucosal damage and colonic MDA, TNF-α and, NF-κB levels in
carvedilol-pretreated group were significantly lower than propranolol-pretreated group.
Conclusion:Both propranolol and carvedilol had a coloprotective effect againstAAinduced
UC depending on their ability to decreases inflammation and oxidative stress
state in rat colon; butcarvedilol had better effects than propranolol. Thus, carvedilol can
be considered the β-blocker of benefit in patients with UC who have other co-existing
diseases indicatingthe use of β-blockers.

The aim of the present study was focused on the development of nanoemulsion of carvedilol, an antihypertensive drug, to be administered through oral route. Twelvenanoemulsionformulations of carvedilol containing different oily phases and different proportions of surfactant-Tween 80 and co-surfactant- PEG 400 were prepared by ultrasonication method and after preliminary evaluation four formulations (F1, F2, F3& F4) were selected for further study. Prepared carvedilol containing nanoemulsions were evaluated for-droplet size and shape through Transmission Electron Microscopy, drug contents and in-vitro drug release patterns through dissolution studies. The entrapment efficiency for various formulations was found to be between 61.02±0.231% to 96.57±0.212%. The drug showed better release rate in comparison to conventional dosage form. All the formulations showed better results in terms of stability. Among the four formulations the best results were found with F1 formulation of carvedilol which gave the highest release of drug 31.28±3.46% after 1 hr and 88.41±2.72% after 24 hrs. The droplet size range in optimized formulation F1, F2, F3 and F4 was found to be between 20.76 to 107.38nm. The droplets were uniform and spherical in shape. It can be concluded that for oral administration of carvedilol a better solubility and bioavailability can be achieved by use of nanoemulsion formulation of the drug which otherwise has poor solubility and bioavailability.