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Showing posts from January, 2023

Liposomal Formulations pharmacokinetics and Tissue Distribution

Distribution of chemotherapeutic agents such as Doxorubicin and Paclitaxel into untargeted organs causes toxicity. Non liposomal Doxorubicin formulation causes myocardium damage that is cumulative and irreversible. In clinical practice, the cumulative dose of Doxorubicin must be limited to reduce cardiotoxicity. The development of chemotherapeutic agents to effectively treat solid tumors depends on the ability of these agents to achieve cytotoxic drug exposure within the tumor(s). Encapsulating common anticancer agents into nanoparticle delivery systems, particularly liposomes, provides a promising approach to enhance delivery at target site. Liposomes are phospholipid bilayer vesicles, which can be used as delivery vehicles for chemotherapeutics. Liposomal Doxorubicin formulations have shown significant therapeutic advantages of lower toxicity and equivalent or higher anti-tumor effects compared to free Doxorubicin formulations. Because only free Doxorubicin has toxicological and ph

Intrathecal pharmacokinetics

  The Intrathecal delivery of compounds acting on central nervous system (CNS) has enhanced interest due to the absence of continuous barriers between the cerebrospinal fluid (CSF) and CNS, which makes only fraction of CSF borne compounds delivered to the brain from the CSF through the perivascular channels. This is significant for macromolecules including biopharmaceuticals, for which the access to CNS from the systemic circulation is particularly hindered due to large molecular size and presence of several vascular barriers such as blood brain, blood-arachnoid and blood-CSF.  In the clinical practice, the most routinely practiced routes for accessing the CSF are Intrathecal (IT) lumbar route and more invasive intracerebroventricular (ICV) route through brain parenchyma. Dosing through Intrathecal is less invasive and chronically used with one dose injections directly intra lumbar region for several months over ICV route. The intrathecal route is currently of significant interest

Genetic Toxicology

Genetic toxicology is a branch of toxicology that evaluates the effects of physical and chemical agents on the genetic material ( Deoxyribonucleic acid ; DNA) and on the genetic processes of living cells.  Genotoxicity refers to the ability of harmful substances including chemical, physical, and biological agents to damage genetic information in cells. Being exposed to biological and chemical agents can result in genomic instabilities and epigenetic alterations, which lead to a variety of diseases, including mutation, which ultimately leads to cancer progression. The National and International regulatory agencies have used genotoxicity data as part of a weight-of-evidence (WOE) approach to assess the potential human carcinogenicity and its corresponding mode of action. The testing patterns and strategies of genotoxic substances are discussed with the purpose of identifying potential human carcinogens, as well as compounds capable of inducing heritable mutations in humans.   Healt

All substances are poisons; there is none which is not a poison. The right dose differentiates a poison - Paracelsus

 Anciently toxicology was known as ‘Science of Poison,’ now a days it is defined as, the study of the effect of chemicals on living organisms and their evaluation as whether these entities are harmful or not or estimating a safe range. For the establishment of safety margins from the adverse effects of chemicals, toxicology depends on few factors like dosage, route of exposure and duration of a certain chemical. The safety level of chemical is decided by the execution of sets of step wise experiments.  Toxicology plays major part in drug development to decide the safe dose and drug response on an exposed organism which includes four disciplines like biology, chemistry, pharmacology and lastly medicine with an intervention of information technology up to some extent. In the current scenario toxicology studies are of great importance in the field of Pharmaceuticals, Agrochemicals and Ayurvedic Products. Pharmaceutical Toxicology : Main concern in pharmaceutical industries is the side eff