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Detailed Calorimetric Analysis of Mixed Micelle Formation from Aqueous Binary Surfactants for Design of Nanoscale Drug Carriers.

ABSTRACT: While numerous papers have been published according to the binary surfactant mixtures, only a few articles provide deeper information on the composition dependence of the micellization, and even less work attempts to apply the enhanced feature of the mixed micelles. The most important parameter of the self-assembled surfactants is the critical micelle concentration (cmc), which quantifies the tendency to associate, and provides the Gibbs energy of micellization. Several techniques are known for determining the cmc, but the isothermal titration calorimetry (ITC) can be used to measure both cmc and enthalpy change (Δ_micH) accompanying micelle formation. Outcomes of our calorimetric investigations were evaluated using a self-developed routine for handling ITC data and the thermodynamic parameters of mixed micelle formation were obtained from the nonlinear modelling of temperature- and composition- dependent enthalpograms. In the investigated temperature and micelle mole fractions interval, we observed some intervals where the cmc is lower than the ideal mixing model predicted value. These equimolar binary surfactant mixtures showed higher solubilization ability for poorly water-soluble model drugs than their individual compounds. Thus, the rapid and fairly accurate calorimetric analysis of mixed micelles can lead to the successful design of a nanoscale drug carrier.

SUBMITTER: Juhasz A

PROVIDER: S-EPMC8703498 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The ability of small interfering RNA (siRNA) to efficiently silence the expression of specific genes provides the basis for exciting new therapies based on RNA interference (RNAi). The efficient intracellular delivery of siRNA from cell uptake through the endosomal trafficking pathways into the cytoplasm remains a significant challenge. Previously we described the synthesis of a new family of diblock copolymer siRNA carriers using controlled reversible addition-fragmentation chain transfer (RAFT) polymerization. The carriers were composed of a positively charged block of dimethylaminoethyl methacrylate (DMAEMA) to mediate siRNA binding and a second pH-responsive endosome releasing block composed of DMAEMA and propylacrylic acid (PAA) in roughly equimolar ratios and butyl methacylate (BMA). Here we describe the development of a new generation of siRNA delivery polymers based on this design that exhibit enhanced transfection efficiency and low cytotoxicity. This design incorporates a longer endosomolytic block with increased hydrophobic content to induce micelle formation. These polymers spontaneously form spherical micelles in the size range of 40 nm with CMC (critical micelle concentration) values of approximately 2 μg/mL based on dynamic light scattering (DLS), (1)H NMR, electron microscopy, and selective partitioning of the small molecule pyrene into the hydrophobic micelle core. The siRNA binding to the cationic shell block did not perturb micelle stability or significantly increase particle size. The self-assembly of the diblock copolymers into particles was shown to provide a significant enhancement in mRNA knockdown at siRNA concentrations as low as 12.5 nM. Under these conditions, the micelle-based systems showed an 89% reduction in GAPDH mRNA levels as compared to only 23% (10 nM siRNA) for the nonmicelle system. The reduction in mRNA levels becomes nearly quantitative as the siRNA concentration is increased to 25 nM and higher. Flow cytometry analysis of fluorescent-labeled siRNA showed uptake in 90% of cells and a 3-fold increase in siRNA per cell compared to a standard lipid transfection agent. These results demonstrate the potential utility of this carrier design for siRNA drug delivery.

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Detailed Calorimetric Analysis of Mixed Micelle Formation from Aqueous Binary Surfactants for Design of Nanoscale Drug Carriers.

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