Pramod Sarpotdar

Percutaneous Absorption Enhancement by Nonionic Surfactants

The influence of nonionic surfactants (polysorbates) on hydrocortisone penetration through hairless mouse skin in vitro has been determined. Permeation was quite slow from purely aqueous media containing surfactants following finite dose application. However, if the vehicle contained high propylene glycol concentrations (40% or more), inclusion of a surfactant increased permeation rate significantly. Similar effects were noted following application of a large donor volume (infinite dose). Synergism was attributed to enhancement of surfactant absorption by the stratum corneum leading to changes in skin barrier resistance. With vehicles containing a surfactant, penetration was higher after finite dose application due to compositional changes within the vehicle.

Tumor Models and the Discovery and Secondary Evaluation of Solid Tumor Active Agents

AbstractEach independently arising tumor is a separate and unique biologic entity with its own unique histologic appearance, biologic behavior, and drug response profile. Thus, in drug discovery, no single tumor has been a perfect predictor for any other tumor. For this reason, new agents are evaluated in a variety of tumor models which is known as breadth of activity testing. In recent years, human tumors implanted in athymic nude mice and SCID mice have also become available for breadth of activity testing. In studies carried out in these laboratories, it was found that 10 human tumors metastasized in the SCID mice, but failed to metastasize in nude mice. In addition, tumor growth and tumor takes were superior in the SCID mice. The strengths and weaknesses of xenograft model systems are discussed. For example, most human tumor xenograft models are excessively sensitive to alkylating agents as well as to a new class of DNA binders (XE840 and XP315). Using human tumor models that are the least sensitive t...