Critical Association Concentration Values Research Articles

Carboxybetaine and Carboxybetaine Ester Derivatives of Tetra(dodecyloxyphenyl)-calix[4]resorcinarene: Synthesis, Self-Assembly and In Vitro Toxicity

Amphiphilic calix[4]resorcinarenes are a class of macrocyclic compounds with broad potential utility including nanomedicine. Here the synthesis of new carboxybetaine and carboxybetaine ester calix[4]resorcinarene bearing 4-(dodecyloxy)phenyl groups on the lower rim is presented. The compounds were characterized by 1H-NMR, 13C-NMR, 2D NMR, IR, ESI and elemental analysis. The critical association concentration values are 1.00 × 10−5 and 1.18 × 10−5 mol·L−1 for carboxybetain and ester, respectively. The hemolytic activity of the macrocycles and their cytotoxicity against normal (WI-38, Chang liver) and tumor cells (M-HeLa) are also estimated.

Synthesis, evaluation and aqueous solution behavior of the cationic fluorinated hydrophobically associating polyacrylamide

Hydroxypropyl acrylate-N-diethyl-perfluorooctane sulfonamide (HAF), a novel surface active cationic fluorinated monomer, is designed and synthesized in this study. The structure of HAF and its intermediate product are characterized by FT-IR and 1H-NMR. Then the hydrophobically associating polyacrylamide (PMHAF) is prepared by free radical polymerization of acrylamide, 2-Acrylamido-2- methylpropane sulfonic acid and HAF in an aqueous solution. The structure and composition of PMHAF are characterized by FT-IR, 1H-NMR, XPS and Tg. Macroscopic and microscopic self-assembly associative properties in solutions of PMHAF are studied via viscosimetry, SEM and AFM. The result show that with the polymer concentration increase, the viscosity increased and the critical association concentration (CAC) is about 1.09 g.L−1. Moreover, the active of PMHAF solution are examined with surface tension, interfacial tension (IFT) and contact angle. The CAC values of PMHAF in water and in salt from surface tension are 1.39 g.L−1 and 1.22 g.L−1 respectively. Copolymers can reduce the interfacial tension between crude oil from Xinjiang Oilfield /water, and the final values of IFT is around 0.0243 mN.m−1 and PMHAF solution has good potential on change of wettability. All of these properties indicate that the fluorinated hydrophobically associating polyacrylamide is an excellent chemical for chemical enhanced oil recovery.

PEG-b-poly (carbonate)-derived nanocarrier platform with pH-responsive properties for pancreatic cancer combination therapy.

A pH-responsive nanoparticle platform, based on PEG-b-poly (carbonate) block copolymers have been proposed that can respond to low pH as found in many cancer micro- and intracellular environment, including that in pancreatic cancer. The hydrophobic domain, i.e., the poly (carbonate) segment has been substituted with tertiary amine side chains, such as N, N'-dibutylethylenediamine (pKa = 4.0, DB) and 2-pyrrolidin-1-yl-ethyl-amine (pka = 5.4, Py) to generate two different sets of block copolymers namely PEG-DB and PEG-PY systems. These side-chain appended amines promote disassembly of nanoparticles and activation of drug release in response to pH conditions mimicking extra- (pH 6.9-6.5) and intracellular compartments (5.5-4.5, from early endosome to lysosome) of cancer tissues respectively. A frontline chemotherapy used for pancreatic cancer, i.e., gemcitabine (GEM) and a Hedgehog inhibitor (GDC 0449) has been used as the model combination to evaluate the encapsulation and pH-dependent release efficiency of these block copolymers. We found that, depending on the tertiary amine side chains appended to the polycarbonate segment, these block copolymers self-assemble to form nanoparticles with the size range of 100-150 nm (with a critical association concentration value in the order of 10-6 M). We also demonstrated an approach where GEM and GDC 0449-encapsulated PEG-DB and PEG-PY nanoparticles, responsive to two different pH conditions, when mixed at a 1:1 vol ratio, yielded a pH-dependent co-release of the encapsulated contents. We envision that such release behaviour can be exploited to gain spatiotemporal control over drug accumulation in pathological compartments with different pH status. The mixture of pH-responsive nanoparticles was found to suppress pancreatic cancer cell proliferation when loaded with anticancer agents in vitro. Cell-proliferation assay showed that both variants of PEG-b-polycarbonate block copolymers were inherently non-toxic. We have also immobilized iRGD peptide on intracellularly activable PEG-DB systems to augment cellular uptake. These targeted nanoparticles were found to promote selective internalization of particles in pancreatic cancer cells and tumor tissue.

Preparation and in vitro characterization of retinoic acid-loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) micelles.

In order to achieve the controlled release of all-trans-retinoic acid (ATRA), poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) copolymer with average molecular weight of 5.34 kDa was synthesized. The nanosized micelles were prepared from copolymer by nano-precipitation method. Critical association concentration (CAC) of micelles was measured by fluorimetry and results indicated low CAC value of micelles (1.9 × 10-3 g/L). ATRA was encapsulated in the core of micelles using different ratios of drug to copolymer. In the case of 10% drug to polymer ratio, more than 80% of the drug was released within 3 days, whereas for ratio of 2% more than 90% of the drug was released within 3 h. The cytotoxic study performed by MTT assay showed that H1299 survival percent decreased significantly (P ≤ 0.05) after exposure to drug-loaded micelles, while no proliferation inhibition effect was observed by either free ATRA or blank PCL-PEG-PCL micelles.

Effect of block lengths on the association behavior of poly(l-lactic acid)/poly(ethylene glycol) (PLA–PEG–PLA) micelles in aqueous solution

A series of poly(l-lactic acid)/poly(ethylene glycol) triblock copolymers with a PLA–PEG–PLA architecture were synthesized by a ring-opening polymerization (ROP) process. The copolymers were characterized by 1H NMR and GPC. The total number average molecular weights were in the range of 4,700–50,000, whereas the degrees of polymerization of the PLA and PEG blocks varied from 15 to 359 and from 68 to 136, respectively. The self-association of these copolymers in aqueous environment was studied by emission fluorescence spectroscopy of anilinonaphthalene probe and the critical association concentration (CAC) of the copolymers was measured. It was found that the micellization process of these copolymers was mainly determined by the length of the hydrophobic LA block, while the length of the hydrophilic PEG block had little effect. Furthermore, the low CAC values of the copolymers suggest that the copolymers form stable supramolecular structures in aqueous solutions.

Synthesis and Self-Assembly of Well-Defined Poly(amino acid) End-Capped Poly(ethylene glycol) and Poly(2-methyl-2-oxazoline)

Poly(ethylene glycol) (PEG) and poly(2-methyl-2-oxazoline) (PMOx) are water-soluble, biocompatible polymers with stealth hemolytic activities. Poly(amino acid) (PAA) end-capped PEG and PMOx were prepared using amino-terminated derivatives of PEG and PMOx as macroinitiators for the ring-opening polymerization of γ-benzyl protected l-glutamate N-carboxyanhydride and S-benzyloxycarbonyl protected l-cysteine N-carboxyanhydride, respectively, in the presence of urea, at room temperature. The molecular weight of the PAA moiety was kept between M(n) = 2200 and 3000 g mol(-1). PMOx was polymerized by cationic ring-opening polymerization resulting in molecular weights of M(n) = 5000 and 10,000 g mol(-1), and PEG was a commercial product with M(n) = 5000 g mol(-1). Here, we investigate the self-assembly of the resulting amphiphilic block copolymers in water and the effect of the chemical structure of the block copolymers on the solution properties of self-assembled nanostructures. The PEG-block-poly(amino acid), PEG-b-PAA, and PMOx-block-poly(amino acid), PMOx-b-PAA, block copolymers have a narrow and monomodal molecular weight distribution (PDI < 1.3). Their self-assembly in water was studied by dynamic light scattering and fluorescence spectroscopy. In aqueous solution, the block copolymers associate into particles with hydrodynamic radii (R(H)) ranging in size from R(H) 70 to 130 nm, depending on the block copolymer architecture and the polymer molecular weight. Larger R(H) and critical association concentration values were obtained for copolymers containing poly(S-benzyloxycarbonyl-l-cysteine) compared to their poly(γ-benzyl-L-glutamate) analogue. FTIR investigations revealed that the poly(γ-benzyl-L-glutamate) block adopts a helical conformation, while the poly(S-benzyloxycarbonyl-L-cysteine) block exists as β-sheet.

Solubilization of methacrylic acid based polymers by surfactants in acidic solutions

The effect of various surfactants on the solubility of methacrylic acid based polyelectrolytes that are insoluble in water at low pH, i.e. isotactic poly(methacrylic acid), i-PMA, Luviflex Soft and Luviflex Silk, was studied by surface tension, fluorescence spectroscopy, potentiometric titration and dynamic light scattering, DLS, measurements. Results show that Luviflex Silk and Luviflex Soft form polymeric micelles in aqueous solutions above a well-defined concentration, whereas both i-PMA and Luviflex Soft undergo a pH-induced conformational transition. The critical association concentration values for each surfactant in the presence of completely ionized polyions were determined. Potentiometric and DLS measurements show that the addition of an anionic and a nonionic surfactant significantly increases the solubility of the polymers at low pH, while the presence of a cationic surfactant results in a formation of an insoluble polymer-surfactant aggregate. The present results could help in regulating the removal of hair-setting polymers by water.

Characterization of hydrophobized pullulan with various hydrophobicities

In this study, we prepared self-assembling nanospheres of hydrophobized pullulan. Pullulan acetate (PA), as hydrophobized pullulan, was synthesized by the acetylation of pullulan. PA derivatives were synthesized by changing the degree of acetylation. PA was characterized by Fourier transform infrared (FT-IR), X-ray diffractometry (XRD), and differential scanning calorimetry (DSC). The particle size distribution of the PA was determined using photon correlation spectroscopy (PCS) and the number-average particle size was found to depend upon the degree of acetylation of PA. Morphology by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed the PA nanospheres were spherical in shape. The fluorescence probe technique was used to study the self-association behavior of hydrophobized pullulans in water using pyrene as a hydrophobic probe. The critical association concentration (CAC) values were determined from the fluorescence excitation spectra, CAC values were dependent upon the degree of acetylation. Drug release studies using clonazepam (CNZ) as a hydrophobic model drug showed that the increased drug contents and increased degree of acetylation resulted in a slower release rate of drug from the nanospheres.

Clonazepam release from core-shell type nanoparticles of poly(ε-caprolactone)/poly(ethylene glycol)/poly(ε-caprolactone) triblock copolymers

The triblock copolymer based on poly(ε-caprolactone) (PCL) as hydrophobic part and poly(ethylene glycol) (PEG) as hydrophilic one was synthesized and characterized. Core-shell type nanoparticles of poly(ε-caprolactone)/poly(ethylene glycol)/poly(ε-caprolactone) (CEC) block copolymer were prepared by a dialysis technique. According to the amphiphilic characters, CEC block copolymer can self-associate at certain concentration and their critical association concentration (CAC) was determined by fluorescence probe technique. CAC value of the CEC-2 block copolymer was evaluated as 0.0030 g/l. CAC values of CEC block copolymer decreased with the increase of PCL chain length, i.e. the shorter the PCL chain length, the higher the CAC values. From the observation of transmission electron microscopy (TEM), the morphologies of CEC-2 core-shell type nanoparticles were spherical shapes. Particle size of CEC-2 nanoparticles was 32.3±17.3 nm as a monomodal and narrow distribution. Particle size, drug loading, and drug release rate of CEC-2 nanoparticles were changed by the initial solvents and the molecular weight of CEC. The degradation behavior of CEC-2 nanoparticles was observed by 1H NMR spectroscopy. It was suggested that clonazepam (CNZ) release kinetics were dominantly governed by diffusion mechanism.