Public Defense of a Ph.D Research Scholar at Department of Pharmacy
- 10:00 am
- Department of Pharmacy, UoP
Hyperlipidemia is among the most common chronic pathological condition, associated with atherogenic events such as blood vessels occlusion, hypertension and plaque formation. The excessive release of cellular reactive oxygen species (ROS) in hyperlipidemia results in blood endogenous antioxidants depletion and oxidative stress. Various treatment protocols of synthetic and natural compounds were developed and applied. Among which the combination therapies were found more effective than individual therapies due to synergistic effects. Natural antioxidants have well reported efficiency in scavenging ROS, preventing the lipid peroxidation and blood antioxidants depletion. Based on different mechanism of actions, availability in local food items and cost, we applied selected dietary antioxidants (AOX) in various combination dose ratios to determine the extent of synergism in hyperlipidemic animal model.
Hyperlipidemia was induced in adult male albino rabbits and alteration in blood lipid profiles and endogenous antioxidants such as glutathione, methionine, N-acetylcysteine, ascorbic acid and α-tocopherol were observed. Further treatments with blends of selected three antioxidants (Oligomeric proanthocyanidins (OPC), niacin (NA) and pterostilbene (PT)) in various ratios were evaluated to get maximum effects. The therapies were designed in individual, two drug and three drug combinations and applied for 12 weeks using atorvastatin for comparison. The total dose of AOX was maintained at 100 mg/kg in each therapy. Blood samples were analyzed periodically to observe change in lipid profiles.
Results showed the effectiveness of natural antioxidants blends treatments and validated the superiority of low dose blends over individual high dose therapies. The two drug combinations (OPC with NA, OPC with PT and NA with PT) were able to reduce LDL/HDL ratio and AI down to levels from -43.2% to -50.30% p <0.001 max and -15.24% to -23.63% p <0.001 max respectively. In individual therapies, the maximum results achieved were -37.08% p <0.001 and -18.52 p <0.001 respectively. The three drug combinations delivered more pronounced effects and retarded LDL/HDL and AI by -59.30% and -25.09% p <0.001 max respectively, observed in 50:30:20 blend of OPC, NA and PT.
Evaluating antioxidants levels in blood, compared to individual therapies, significant up-regulation was observed in methionine, GSH and NAC up to 35.08 ± 1.60 μmol/l, 3.82 ± 0.47 μmol/l and 4.21 ± 0.425 μmol/l (p < 0.001 each) respectively in combination therapies against the disease control (19.30 ± 1.18 μmol/l, 3.01 ± 0.28 μmol/l and 3.73 ± 0.412 μmol/l). The all-trans retinoic acid level raised parallel with the lipid levels in disease control (4.48 ± 0.24 μmol/l) while retarded by treatment down to 3.26 ± 0.12 μmol/l (p <0.001) max. Similarly homocysteine levels were also significantly controlled. The results were comparable with the statin therapy regarding lipid lowering effects while more significant in sparing endogenous antioxidants.
For optimized AOX blend, stable formulations in half doses will least excipients number and quantities were developed. The compatibility tests via FTIR, drug content and physical consistency of the admixtures were conducted. A novel HPLC-UV method was developed using cetrimide as amphiphilic ion pairing agent for NA and PT analysis. Method was successfully applied to plasma and dissolution samples. The OPC was analyzed using reported muriatic acid method.
By reason of wetting problem and poor flowability, the granulation technique was followed using dry granulation, wet granulation with deionized water and with 2% PVP-K30. Mixtures were compressed into oblong shallow concave punches at the adjusted weight of 880 mg/tab. Lab formulations produced fair to good results regarding precompresion properties, disintegration and in-vitro release. Using cross carmellose sodium individually (F6) in high quantity or in low ratio combination with sodium starch glycolate (F7) produced good disintegration and drug release profiles. However all the formulations released all three drugs within the standard limits of uncoated units.
The present study supports and signifies the use of natural AOX blends besides conventional therapies for superior controlled outcome. This will ultimately lead to the reduced side effects of conventional drugs in concurrent long term use.