Dasatinib and Quercetin: Short-term Simultaneous Administration Yields Senolytic Effect in Humans | Chapter 04 | Issues and Developments in Medicine and Medical Research Vol. 2

 Background: The higher the number of cell divisions, the more senescent cells. In human and animal beings, senescent cells are one of the most poisonous cells. When their number reaches a certain level, it causes a lot of ageing indicators to appear. During the division phase, the cell's generation reaches ultimate morphogenetic state, according to the citogenetic centriolar hypothesis of ageing. As a result, programmed cell death (apoptosis) must be triggered; otherwise, the cell would enter a senescent state if it does not kill itself.

Senescent cells are responsible for age-related diseases. Partially eliminating senescent cells should theoretically result in increased life capacity. On Ercc1 -/ mice, this idea was confirmed. Dasatinib and quercetin were given to Ercc1 -/ mice on a regular basis, extending their lifespan and postponing age-related signs and diseases. We decided to put dasatinib and quercetin together to see if they had a senolytic effect in humans.

The clinical trial was conducted on 64 male volunteers over the age of 36 for this objective. To put things in perspective, our volunteers were divided into four groups, each with 16 members. Within 5 days, the D+Q group was given 50 mg of dasatinib and 500 mg of quercetin orally.

Methods: The entire trial was supplemented with thorough medical screening and a stair ascending test in order to register and analyse changes caused by the medication components.

As a consequence, 50mg of dasatinib combined with 500 mg of quercetin had a clear senolytic effect, which was supported by improved stair ascending test results and a calmed state of systolic blood pressure. This dosage combination of these two drugs is almost certainly safe.

Author(S) Details

Tkemaladze Jaba
International Longevity Centre- 0131, King Demetre Tavdadebuli 81, Tbilisi, Georgia.

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Determining the Enhancement of Oral Bioavailability VIA Solid Lipid Nanoparticles of Anticancer Drug Dasatinib - An In-vitro Cytotoxicity and Pharmacokinetic Study | Chapter 14 | Current Aspects in Pharmaceutical Research and Development Vol. 2

 Dasatinib (DST) is a Biopharmaceutics Classification System Class II medication with a high permeability and very low solubility. DST's low water solubility and poor dissolution result in low bioavailability. As a result, restricted aqueous solubility represents a bottleneck for DST's therapeutic success. Due to a large first-pass effect, animal research suggests that DST has an absolute bioavailability of 14–34 percent. Lipid-based drug delivery technologies, such as solid lipid nanoparticles (SLNs), can be utilised to circumvent hepatic first-pass metabolism and improve oral bioavailability. Methods: Submicron colloidal carriers with a size range of 50–1000 nm are known as SLNs. These are made from physiological lipids that have been distributed in water or an aqueous surfactant solution. By utilising intestinal lymphatic transport, DST can be easily loaded into SLNs to boost oral bioavailability. In a bioavailability research in rats, an ideal system was compared to that of DST suspension (SUS). Results: ATCC cell lines were used in an in vitro cytotoxicity research using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay technique, the percent inhibition was higher in SLN than in SUS. The pharmacokinetics of DST-SLNs in male Wistar rats following oral administration were investigated. When compared to a DST SUS, DST's bioavailability was improved by 2.28 times. Conclusion: The findings suggest that SLNs are a good lipid-based carrier system for increasing DST oral bioavailability.

Author(s) Details

A. A. Mohamed Yasir Arafath      
Department of Pharmacy Practice, Vinayaka Mission’s College of Pharmacy, Salem, Tamil Nadu, India.

B. Jaykar
Vinayaka Mission’s Research Foundation (Deemed to be University), Salem, Tamil Nadu, India.

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