Interactions between poloxamer, PEOx-PPOy-PEOx, and non-ionic surfactant, sucrose monolaurate: A study on potential allergenic effect using model phospholipid membrane.

Sugar-based surfactants are involved in skin related allergy cases in the past decade. Skin irritation starts with the interaction of the surfactant with the skin lipids leading to lipid emulsification and eventual barrier damage. Polymers or co-surfactants can be used to mitigate the allergenic effect but the mechanism of formulation mildness on skin remains unclear. We have used the quartz crystal microbalance (QCM) together with dissipative particle dynamics (DPD) simulation, small angle x-ray scattering (SAXS) as well as cell viability tests to decipher the interactions between poloxamers and sucrose monolaurate (SML), and how these interactions could prevent the disruption of a model supported phospholipid bilayer (SLB). Poloxamer addition to the SML solution can delay or totally prevent the disruption of the SLB depending on poloxamer type and concentration. Poloxamer P407 (Pluronic® F127) delays the onset of disruption while poloxamer P188 (Pluronic® F68) does not preserve the bilayer integrity even at high concentration of up to 15% w/w. Preservation of the SLB is likely due to the differences in the aggregates formation between SML-F127 and SML-F68 mixtures with corresponding retarded motion of SML micelles through the SML-F127 polymer matrix that improved cell viability.

High molecular weight hyper-branched PCL-based thermogelling vitreous endotamponades.

Vitreous endotamponades play essential roles in facilitating retina recovery following vitreoretinal surgery, yet existing clinically standards are suboptimal as they can cause elevated intra-ocular pressure, temporary loss of vision, and cataracts while also requiring prolonged face-down positioning and removal surgery. These drawbacks have spurred the development of next-generation vitreous endotamponades, of which supramolecular hydrogels capable of in-situ gelation have emerged as top contenders. Herein, we demonstrate thermogels formed from hyper-branched amphiphilic copolymers as effective transparent and biodegradable vitreous endotamponades for the first time. These hyper-branched copolymers are synthesised via polyaddition of polyethylene glycol, polypropylene glycol, poly(ε-caprolactone)-diol, and glycerol (branch inducing moiety) with hexamethylene diisocyanate. The hyper-branched thermogels are injected as sols and undergo spontaneous gelation when warmed to physiological temperatures in rabbit eyes. We found that polymers with an optimal degree of hyper-branching showed excellent biocompatibility and was able to maintain retinal function with minimal atrophy and inflammation, even at absolute molecular weights high enough to cause undesirable in-vivo effects for their linear counterparts. The hyper-branched thermogel is cleared naturally from the vitreous through surface hydrogel erosion and negates surgical removal. Our findings expand the scope of polymer architectures suitable for in-vivo intraocular therapeutic applications beyond linear constructs.

Self-assembly of didodecyldimethylammonium surfactants modulated by multivalent, hydrolyzable counterions.

The self-assembly behavior of double-chained didodecyldimethylammonium (DDA(+)) surfactants with hydrolyzable phosphate (PO4(3-), HPO4(2-), and H2PO4(-)), oxalate (HC2O4(-) and C2O4(2-)), and carbonate (HCO3(-)/CO3(2-)) counterions was found to depend on both the counterion and its hydrolysis state, as determined by the pH of the system. Carbonate and phosphate ions at all hydrolysis states successfully stabilize an extended isotropic micellar solution region. These micelles are well-described as prolate ellipsoids which vary in size and aspect ratio depending on the surfactant concentration and hydrolysis state of the counterion. Both oxalate counterions form bilayer structures in dilute solution. The structures found with divalent oxalate, C2O4(2-), ions possessed very limited swelling capacity compared to the bilayer structures formed with monovalent oxalate, HC2O4(-), ions. The lamellar (Lα) phase was universally formed at sufficiently high surfactant concentrations for all hydrolyzable counterions. Two intermediate structures corresponding to a disordered mesh (Lα(D)) and tetragonal ordered mesh (T) phase were found to form with DDA2HPO4 prior to the Lα phase but not with other phosphate counterions.

Hexagonal closest-packed spheres liquid crystalline phases stabilised by strongly hydrated counterions.

The sequence and structure of lyotropic liquid crystals formed in C12-C16 alkyltrimethylammonium surfactants with hydrolysable and multivalent phosphate (PO4(3-), HPO4(2-) and H2PO4(-)), oxalate (HC2O4(-) and C2O4(2-)), and carbonate (HCO3(-)/CO3(2-)) counterions were determined using a concentration gradient method coupled with polarising optical microscopy and small angle X-ray scattering. In addition to the discrete cubic (I1, space group Pm3n) and hexagonal (H1, p6m) phases, almost all of these surfactants also formed the (previously) rare hexagonally closest-packed spheres (HCPS, P63/mmc) phase at compositions between the Pm3n cubic and L1 micellar phases. This structure has not been previously observed in cationic surfactants, but is readily achieved by using strongly hydrated counterions to stabilise spherical micelles at high concentrations.

A rocket-like encapsulation and delivery system with two-stage booster layers: pH-responsive poly(methacrylic acid)/poly(ethylene glycol) complex-coated hollow silica vesicles.

Rocket-like vesicles formed are composed of poly(acrylic aicd) (PMAA )/poly(ethylene glycol) (PEG) complex coated hollow silica spheres, and the structure and composition of the vesicles are characterized using TGA, (1)H NMR, FTIR, and TEM. Although only one-third of EG units of PEG brushes grafted to hollow silica spheres form the complex with PMAA via hydrogen bonding, the first "booster" layer composed of PMAA/PEG complex can provide secure encapsulation of model compound calcein blue under an acidic condition. The second "booster" layer composed of PEG brushes can be formed by changing acidic pH to 7.4 through the disassociation of the PMAA/PEG complex. A higher molecular weight PMAA exhibits a faster disassembly due to the formation of a looser PMAA/PEG complex on the surfaces of hollow silica spheres.

Resiliently spherical micelles of alkyltrimethylammonium surfactants with multivalent, hydrolyzable counterions.

A series of C(12)-C(16) alkyltrimethylammonium surfactants with hydrolyzable phosphate (PO(4)(3-), HPO(4)(2-), and H(2)PO(4)(-)), oxalate (HC(2)O(4)(-) and C(2)O(4)(2-)), and carbonate (HCO(3)(-) and CO(3)(2-)) counterions have been prepared, and their micellar solution behavior has been characterized. Critical micelle concentrations were measured using electrical conductivity and were found to depend on both the counterion and its hydrolysis state. All monovalent counterions bind less strongly to the micelle surface than does bromide or chloride, whereas multivalent species bind more strongly. Small-angle neutron scattering reveals that, unlike alkyltrimethylammonium bromides and chlorides, micelles are small and spherical in the presence of hydrolyzable counterions of all valences and remain spherical even in the presence of added electrolyte. This is consistent with the strong solvation of even strongly bound hydrolyzable counterions, which prevents the screening of repulsions between adjacent headgroups necessary for sphere-cylinder transformations. Salts of multivalent hydrolyzable counterions could thus be used to control the micelle structure in novel ways.