Haiqing Yin

Physicochemical characteristics of pH-sensitive poly(l-Histidine)-b-poly(ethylene glycol)/poly(l-Lactide)-b-poly(ethylene glycol) mixed micelles

A novel pH-sensitive polymeric micellar system composed of poly(L-histidine)-b-poly(ethylene glycol) and poly(L-lactide)-b-poly(ethylene glycol) block copolymers was studied by dynamic/static light scattering, spectrofluorimetry and differential scanning calorimetry. The mixed micelles displayed ultra Ph Sensitivity Which Could Be Tuned By Varying The Mixing Ratio Of The Two Polymers. In Particular, Mixed Micelles Composed Of 25 Wt.% Poly(L-lactide)-b-poly(ethylene glycol) exhibited desirable pH dependency which could be used as a drug delivery system that selectively targeted the extracellular pH of acidic solid tumors. Micelles were quite stable from pH 7.4 to 7.0 but underwent a two-stage destabilization as pH decreased further. A significant increase in size and aggregation number was observed when pH dropped to 6.8. Further disruption of the micelle core eventually caused phase separation in the micelle core and dissociation of ionized poly(L-histidine)-b-poly(ethylene glycol) molecules from the micelles as pH decreased to 6.0. Increased electrostatic repulsions which arise from the progressive protonation of imidazole rings overwhelming the hydrophobic interactions among uncharged neutral blocks is considered to be the mechanism for destabilization of the micelle core.

Microstructures and rheological dynamics of viscoelastic solutions in a catanionic surfactant system

Viscoelastic solutions formed in a catanionic surfactant system of dodecyltriethylammonium bromide (DTEAB)/sodium dodecylsulfate (SDS) at the molar ratio of 27/73 were systematically studied using a combination of rheology and dynamic light scattering (DLS). Wormlike micelles began to form above the total surfactant concentration (C(total)) of 120 mM by the growth of small cylindrical micelles. Subsequently the system was found to exhibit linear viscoelasticity with characteristic of a Maxwell fluid in the intermediate concentration range of 170-210 mM, which arose from a 3D entangled network of wormlike micelles. At higher surfactant concentrations, a transition from linear micelles to branched structures probably took place. Finally and significantly, the effect of the surfactant headgroup on the rheological property of catanionic surfactant mixtures was discussed.

Effects of cholesterol incorporation on the physicochemical, colloidal, and biological characteristics of pH-sensitive AB2 miktoarm polymer-based polymersomes

In our previous study, a histidine-based AB2 miktoarm polymer, methoxy poly(ethylene glycol)-b-poly(l-histidine)2 (mPEG-b-(PolyHis)2), was designed to construct pH-sensitive polymersomes that transform in acidic pH; the polymer self-assembles into a structure that mimics phospholipids. In this study, the polymersomes further imitated liposomes due to the incorporation of cholesterol (CL). The hydrodynamic radii of the polymersomes increased with increasing CLwt% (e.g., 70 nm for 0 wt% vs. 91 nm for 1 wt%), resulting in an increased capacity for encapsulating hydrophilic drugs (e.g., 0.92 μL/mg for 0 wt% vs. 1.42 μL/mg for 1 wt%). The CL incorporation enhanced the colloidal stability of the polymersomes in the presence of serum protein and retarded their payload release. However, CL-incorporating polymersomes still demonstrated accelerated release of a hydrophilic dye (e.g., 5(6)-carboxyfluorescein (CF)) below pH 6.8 without losing their desirable pH sensitivity. CF-loaded CL-incorporating polymersomes showed better cellular internalization than the hydrophilic CF, whereas doxorubicin (DOX)-loaded CL-incorporating polymersomes presented similar or somewhat lower anti-tumor effects than free hydrophobic DOX. The findings suggest that CL-incorporating mPEG-b-(PolyHis)2-based polymersomes may have potential for intracellular drug delivery of chemical drugs due to their improved colloidal stability, lower drug loss during circulation, acidic pH-induced drug release, and endosomal disruption.