Small-angle neutron scattering studies of microenvironmental and structural changes of Pluronic micelles upon encapsulation of paclitaxel

Abstract

Pluronic micelles represent a novel type of nanocarriers that enhance the therapeutic efficacy of paclitaxel (PTX) by increasing its solubility and circulation time. However, encapsulation or incorporation of a drug influences the micellar structure and subsequently alters the pharmacokinetic behavior of the drug delivery system. In this study, we investigated the structural properties of micelles after micellar solubilization of PTX. Proton nuclear magnetic resonance ( 1 H NMR) and Fourier transform infrared spectroscopy (FTIR) studies showed that PTX was incorporated into the poly (propylene oxide) (PPO) blocks of the micelle cores. Smallangle neutron scattering (SANS) was used to probe changes in the core-shell structure of Pluronic P123 micelles as a function of increasing PTX and Pluronic concentration. Modelindependent analyses and cryogenic-transmission electron microscopy (cryo-TEM) confirmed that both pure and PTX-incorporated micelles were spherical. However, an increase in PTX concentration led to a slight increase in the micellar dimension and was associated with the appearance of the larger Pluronic-drug aggregates as confirmed by evaluation of cryo-TEM images. At higher Pluronic concentration and a constant PTX concentration, the dimensions of micelles increased, most likely due to the altered hydrophobic environment promoting the interaction of PPO and poly (ethylene oxide) (PEO) blocks.

Formulation of Poloxamers for Drug Delivery

“…The emulsion droplet size depends on surface tension and viscosity and so can be tuned by variation of the organic solvent type to influence the droplet surface area. The structure of micellar solutions of Pluronic ® P123 and Paclitaxel formed via the emulsification-solvent evaporation method using acetonitrile was studied by small-angle neutron scattering (SANS) at concentrations above the cmc [ 141 ]. The micelles formed were stable and well-described by a core-shell model, but the core radius (ranging from 34 to 37 Å) did not change significantly upon increasing the concentration of Paclitaxel despite the fact that the quantity of the solubilized drug increased [ 141 ].…”

“…The structure of micellar solutions of Pluronic ® P123 and Paclitaxel formed via the emulsification-solvent evaporation method using acetonitrile was studied by small-angle neutron scattering (SANS) at concentrations above the cmc [ 141 ]. The micelles formed were stable and well-described by a core-shell model, but the core radius (ranging from 34 to 37 Å) did not change significantly upon increasing the concentration of Paclitaxel despite the fact that the quantity of the solubilized drug increased [ 141 ]. The finding was attributed to Paclitaxel crystal growth as the acetonitrile was evaporated from the system (the solutions were centrifuged to remove large crystals).…”

“…The finding was attributed to Paclitaxel crystal growth as the acetonitrile was evaporated from the system (the solutions were centrifuged to remove large crystals). TEM imaging showed that P123 adsorbed along large Paclitaxel crystals (when they were not removed via centrifugation) [ 141 ].…”

Dual Interactions of Amphiphilic Gelatin Copolymer and Nanocurcumin Improving the Delivery Efficiency of the Nanogels

“…The emergence of micelle packing with well-design at the higher level complex formulation, which comes from the approaching the concept of biological macromolecules as protein, have proven to be an excellent candidate in drug delivery system field of amphiphilic block copolymer [5,6]. Various supramolecular micelles as the large complex micelles [7,8,9], multicompartment micelles [10,11] and large compound micelles/vesicles [12] have been received via the modification of amphiphilic block copolymer. Among these, we have developed several approaches to obtain complex self-assemblies of amphiphilic block copolymer [4,8], in which specific interactions, mainly hydrophobic–hydrophobic interactions connect the core and shell.…”

“…Self-assemble offers tremendous potential as a method to fabricate the complex micelles in the form of multicore [7,8,9,10,11,12]. In particular, the self-assembled process, the uniform structure with the controllable size of these particles are still the remaining problem [9].…”