Chirality seems to be a pivotal technique in the field of science. Research teams are quite well versed in empirical separation, however, at the same time, they are clueless about the evolution of chiral separation. As per the guidelines of the United States Food and Drug Administration (US FDA), chiral drugs must be untangled before they are sold to the public. Stereogenic separation has gained prominence during the last 10 decades due to the disparate biological function of enantiomers in the stereogenic environment. Chiral drugs exhibit a wide range of bioavailability, distribution, and pharmacodynamic properties concomitantly they exert divergent pharmacological and toxicological properties. Enantiomeric chiral products could be considered safe and potent in combating various diseases including metabolic diseases like diabetes. Several studies have delineated the development of a novel analytical and bioanalytical method to detect/segregate/quantify chiral chemical components in medicinal chemistry. The same physicochemical characteristics of enantiomers have been proven to be beneficial to the estrangement of stereogenic compounds. Furthermore, the advancement of bioanalytical methods is also critical to shedding light on the destiny of distinct enantiomers in the biological environment. HPLC (High-Performance Liquid Chromatography) and CE (Capillary Electrophoresis) have been the most commonly employed separation techniques. But the technical advances are required to enhance the efficiency of detection and quantification of chiral molecules on a large scale. The current review delineates the need for the chiral separation of stereogenic antidiabetic drug compounds with technical advances. Furthermore, this research is focused on the enantioseparation of chiral antidiabetic drugs and a brief overview of the analytical and bioanalytical methods conducted on distant chiral antidiabetic drugs to improve the efficiency of chiral separation.
Background Cyclosporine (CsA)is used as an antifungal, immunosuppressant administered orally. But it exhibit poor aqueous solubility due to the presence of lipophilic, cyclic endecapeptide in large fraction, which makes poor permeability across the membranes. So, liquid crystallinenano formulation could enhance the solubility properties. However, to date, there is no analytical method development or validation pertinent to cyclosporine (CsA) as liquid crystalline Nano formulations. Objective To develop and validate a simple and quick reverse phase, high-performance liquid chromatographic method for determination of cyclosporine (CsA) using UV detector. Employ the method to determine drug loading (%DL), drug entrapment efficiency (%DEE) and to quantify drug release samples. Methods The mobile phase included acetonitrile and 10Mm ammonium acetate as a buffering media. In the ratio 90:10 (ACN: Ammonium Acetate, pH 4) using Shim-pack GIST C18 (4.6 x 100 mm, 5 µm). Column with flow rate of 0.8ml/min, with column temperature (50 ºC), the eluent detected at 215nm with injection volume 20µl. Results The determination of cyclosporine (CsA) was accurate and precise based on the data pertinent to system adaptability, accuracy, linearity, precision, specificity, and robustness. This approach was validated in accordance with ICH guidelines. The LOD & LOQ found to be 0.12 µg/ml and 0.15µg/ml. According to the approach, the linearity was in the range of 1–64 µg/ml. It has been claimed that cyclosporine (CsA) recovery rates range from 98 to 100%. Because there was no invasion from excipients or mobile phase, the strategy was proven to be accurate. Cyclosporine (CsA) has a run time of around 10 minutes. The calibration curve was accurate. Cyclosporine (CsA) elution time was 4.56 minutes. The accuracy of the system was 98.2% respectively, and the %RSD was less than 2%. The % entrapment efficiency of CsA -LCN was found to be 83.13%. Whereas the % DL for CsA -LCN was found to be 5.90 ± 0.31. Drug release profile showed a sustained release pattern for CsA -LCN in comparison to pure drug Conclusion RP-HPLC method is a sensitive, precise, accurate method for analytical method development and validation specifically for (CsA) in liquid crystalline nanoparticles.
: Peroxisome proliferator activated receptors (PPARs) activity exhibit significant implications for the development of novel therapeutic modalities against neurodegenerative diseases. PPAR-α, PPAR-β/δ, and PPAR-γ nuclear receptors expression are significantly reported in the brain, their implications in brain physiology and other neurodegenerative diseases still require extensive studies. PPAR signaling can modulate various cell signaling mechanisms involved inside the cells contributing to on- and -off target actions selectively to promote therapeutic effects as well as the adverse effects of PPAR ligands. Both natural and synthetic ligands for the PPARα, PPARγ, and PPARβ/δ have been reported. PPARα (WY 14.643) and PPARγ agonists can confer neuroprotection by modulating mitochondrial dynamics through the redox system. The pharmacological effect of these agonists may deliver effective clinical responses by protecting vulnerable neurons to Aβ toxicity in Alzheimer’s disease (AD) patients. Therefore, the current review delineated the ligands interaction with 3D- PPARs to modulate neuroprotection and also deciphered the efficacy of numerous drugs viz., Aβ aggregation inhibitors, vaccines, and γ-secretase inhibitors against AD; this review elucidated the role of PPAR and their receptor isoforms in neural systems, and neurodegeneration in human beings. Further, we have substantially discussed the efficacy of PPREs as potent transcription factors in the brain, and the role of PPAR agonists in neurotransmission, PPAR gamma coactivator-1α (PGC-1α), and mitochondrial dynamics in neuroprotection during AD conditions. This review concludes with the statement; development of novel PPARs agonists may benefit patients with neurodegeneration mainly in AD patients to mitigate the pathophysiology & dementia subsequently to improve overall patient’s quality of life.
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