Therapeutic approaches to drug targets in atherosclerosis

AbstractNon-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPARα, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis

DEVELOPMENT OF RITONAVIR LOADED NANOPARTICLES: IN VITRO AND IN VIVO CHARACTERIZATION

 Objective: The purpose of the present investigation was to develop a nanosuspension to improve dissolution rate and oral bioavailability of ritonavir.Methods: Extended-release ritonavir loaded nanoparticles were prepared using the polymeric system by nanoprecipitation technique. Further, the effect of Eudragit RL100 (polymeric matrix) and polyvinyl alcohol (surfactant) was investigated on particle size and distribution, drug content, entrapment efficiency, and in vitro drug release from nanosuspension where a strong influence of polymeric contents was observed. Drug-excipient compatibility and amorphous nature of drug in prepared nanoparticles were confirmed by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies, respectively.Results: Hydrophobic portions of Eudragit RL100 could result in enhanced encapsulation efficiency. However, increase in polymer and surfactant contents lead to enlarged particle size proportionately as confirmed by transmission electron microscopy. Nanosuspension showed a significant rise in dissolution rate with complete in vitro drug release as well as higher bioavailability in rats compared to the pure drug.Conclusion: The nanoprecipitation technique used in present research could be further explored for the development of different antiretroviral drug carrier therapeutics

Assessment of anti-inflammatory potential of Sesbania bispinosa Linn. leaf extracts and fractions by acute and

Aim and objectives: Leaf extracts and fractions of S. bispinosa were evaluated for anti-inflammatory activity in mice using acute and chronic anti-inflammatory models with aspirin as a reference drug. Materials and methods: Methanol, chloroform and hexane were used to prepare leaf extracts by soxhlet extraction method, while acetone, ethyl acetate and petroleum ether were used to prepare fractions of most active extract. These extract and fractions were evaluated by using carrageenan and formalin-induced inflammation models in albino mice. Extracts and fractions at the dose 250 mg/kg/p.o. and aspirin at 100 mg/kg/p.o. were used for the study. Results: Methanolic extract of S. bispinosa (MELSB) revealed significant anti-inflammatory activity which is indicated by 15.22% inhibition of paw edema at 180 min in carrageenan model, while ethyl acetate fraction of methanolic extract showed 16.26% and 15.50% inhibition of paw edema and thickness in carrageenan and formalin models respectively. In chronic model, just like aspirin, time-dependent activity was observed with acetone and ethyl acetate fractions; the greater reduction in paw thickness was observed with ethyl acetate fraction (∗∗p < 0.01). Conclusion: The results of the present study suggest that leaves of S. bispinosa possess significant level of anti-inflammatory activity and ethyl acetate fraction may be further explored as an anti-inflammatory remedy as it was found to possess higher anti-inflammatory activity among all extracts and fractions as demonstrated in both acute and chronic models

Antiarthritic Potential of <i>Calotropis procera</i> Leaf Fractions in FCA-Induced Arthritic Rats: Involvement of Cellular Inflammatory Mediators and Other Biomarkers

Calotropis procera (commonly known as Swallow wort) is described in the Ayurvedic literature for the treatment of inflammation and arthritic disorders. Therefore, in the present work, the antiarthritic activity of potential fractions of Swallow wort leaf was evaluated and compared with standards (indomethacin and ibuprofen). This study was designed in Wistar rats for the investigation of antiarthritic activity and acute toxicity of Swallow wort. Arthritis was induced in Wistar rats by injecting 0.1 mL of Freund’s complete adjuvant (FCA) on the 1st and 7th days subcutaneously into the subplantar region of the left hind paw. Evaluation of our experimental findings suggested that antiarthritic activity of methanol fraction of Swallow wort (MFCP) was greater than ethyl acetate fraction of Swallow wort (EAFCP), equal to standard ibuprofen, and slightly lower than standard indomethacin. MFCP significantly reduced paw edema on the 17th, 21st, 24th, and 28th days. It also showed significant effect (p < 0.01) on arthritic score, paw withdrawal latency, and body weight. The inhibition of serum lysosomal enzymes and proinflammatory cytokines along with improvement of radiographic features of hind legs was also recorded with MFCP. Finally, it was concluded that MFCP can be a feasible therapeutic candidate for the treatment of inflammatory arthritis