Nanosolvated microtubule-modulating chemotherapeutics: a case-to-case study.

About 10% of the drugs in the preclinical stage are poorly soluble, 40% of the drugs in the pipeline have poor solubility, and even 60% of drugs coming directly from synthesis have aqueous solubility below 0.1 mg/ml. Out of the research around, 40% of lipophilic drug candidates fail to reach the market despite having potential pharmacodynamic activities. Microtubule-modulating chemotherapeutics is an important class of cancer chemotherapy. Most chemotherapeutics that belong to this category are plant-derived active constituents, such as vincristine, vinblastine, colchicine, docetaxel, paclitaxel, and noscapinoids. The pKa of a drug considerably affects its solubility in physiological fluids and consequently bioavailability. It usually ranges from 5 to 12 for microtubule-modulating drugs. Hence, the solubility of these drugs in physiological fluids is considerably affected by a change in pH. However, because of unpredictable parameters involved in poor solubility and the low oral bioavailability of these chemotherapeutics during the early phases of drug development, they often have an unusual pharmacokinetic profile. This makes the development process of novel chemotherapeutics slow, inefficient, patient-unfriendly, and very costly, emphasizing a need for more rational approaches on the basis of preclinical concepts. Nanosolvation is a process of increasing the polarity of a hydrophobic molecule either by solvation or cavitization in a hydrophilic macrocycle. The present review therefore focuses on the techniques applied in nanosolvation of microtubule-modulating chemotherapeutics to enhance solubility and bioavailability. The methodologies described will be highly beneficial for anticancer researchers to follow a trend of rational drug development.

Antipsychotic activity of aqueous ethanolic extract of tinospora cordifolia in amphetamine challenged mice model.

Tinospora cordifolia is reported to have CNS active principle and is used for the treatment of various neurological disorders. Hence, the effect of aqueous ethanolic extract of Tinospora cordifolia was investigated for its putative antipsychotic activity using amphetamine challenged mice model. Haloperidol (1 mg/kg i.p.) was administered acutely to mice as standard drug. Control animals received vehicle (10% DMSO). The in vivo receptor binding studies were carried out to correlate the antipsychotic activity of the extract with its capacity to bind to the DAD2 receptor. The results in SLA showed that the hydro alcoholic extract of the stems of Tinospora cordifolia at a dose level of 250 mg/kg and 500 mg/kg showed no significant antipsychotic activity in amphetamine induced hyperactivity in mice when compared to standard. Extract alone treated group at a dos level of 250 mg/kg and 500 mg/kg showed a decreased in locomotor activity when compared to the control. The plant extract increased the DAD(2) receptor binding in a dose dependent manner in treated mice compared to the control group.