Switching from endogenous to exogenous delivery of a model drug to DNA through micellar engineering

Abstract

A potential strategy has been demonstrated, for the first time, for switching the mode of delivery of drugs or small molecular systems from endogenous to exogenous, simply by engineering the chain length of micellar carriers. Ethidium bromide (EB) is exploited as the model drug which has been successfully delivered to natural DNA through endogenous and exogenous modes by tuning the chain length of anionic sodium n-alkyl sulfate micelles. β-cyclodextrin (β-CD) is exploited as an extrinsic stimulant for the exogenous delivery of EB to DNA. Multi-spectroscopic techniques involving absorption, emission, fluorescence anisotropy, fluorescence decay analysis, circular dichroism, DNA helix melting etc. have established tuning of the delivery mode between endogenous and exogenous. Differential binding affinity of the model drug with different micelles of varying chain length relative to that with DNA is capitalized to make the switching feasible. Although endogenous mode avoids external stimulant and associated problems, a regulation of the stimulant concentration makes the other mode controllable and quantitative. With appropriate choice of carrier micelle and modulation of this developed strategy can radically change the therapeutic research enabling one to take a control over the drug delivery mode to exploit the advantage of one or the other selectively, whenever required.

Keywords: Bioactive probe; DNA; Endogenous and exogenous delivery; Ethidium bromide; Micellar engineering; Targeted drug delivery.