Micellar Structure In Aqueous Solution Research Articles

Amphiphilic block copolymers of poly(N-vinyl pyrrolidone) and poly(isobornyl methacrylate). Synthesis, characterization and micellization behaviour in selective solvents

Block copolymers of N-vinyl pyrrolidone (NVP) and isobornyl methacrylate (IBMA), PIBMA-b-PNVP, were prepared employing the RAFT polymerization technique. IBMA was polymerized first followed by the polymerization of NVP in the presence of a suitable fluoroalcohol to accelerate the crossover reaction. The copolymers were characterized by Size Exclusion Chromatography (SEC) and NMR spectroscopy. The thermal stability of these copolymers was studied via Thermogravimetric Analysis (TGA) and Differential Thermogravimetry (DTG), showing unique characteristics compared to the respective PIBMA and PNVP homopolymers. The micellization behavior was studied in THF, which is a selective solvent for the PIBMA blocks. The corresponding statistical copolymers, PNVP-stat-PIBMA were also examined to elucidate the effect of the macromolecular architecture on the micellar properties. Furthermore, the self-assembly behavior in aqueous solutions was studied for the PIBMA-b-PNVP block copolymers. Water is a selective solvent for the PNVP blocks. Static (SLS) and dynamic light scattering (DLS) were employed to study the micellar assemblies. The encapsulation of the hydrophobic compound curcumin within the micellar core of the micellar structures in aqueous solutions was investigated by UV–Vis spectroscopy and DLS measurements.

An Antigen Capture Assay for the Detection of Mycolactone, the Polyketide Toxin of Mycobacterium ulcerans.

Mycolactone is a cytotoxin responsible for most of the chronic necrotizing pathology of Mycobacterium ulcerans disease (Buruli ulcer). The polyketide toxin consists of a 12-membered lactone ring with a lower O-linked polyunsaturated acyl side chain and an upper C-linked side chain. Mycolactone is unique to M. ulcerans and an immunological Ag capture assay would represent an important tool for the study of Buruli ulcer pathogenesis and for laboratory diagnosis. When testing sets of mycolactone-specific mouse mAbs, we found that Abs against the hydrophobic lower side chain only bind mycolactone immobilized on a solid support but not when present in solution. This observation supports previous findings that mycolactone forms micellar structures in aqueous solution with the hydrophobic region sequestered into the inner core of the aggregates. Although an Ag capture assay typically requires two Abs that recognize nonoverlapping epitopes, our search for matching pairs of mAbs showed that the same mAb could be used both as capture and as detecting reagent for the detection of the mycolactone aggregates. However, the combination of a core-specific and a core/upper side chain-specific mAb constituted the most sensitive ELISA with a sensitivity in the low nanogram range. The results of a pilot experiment showed that the sensitivity of the assay is sufficient to detect mycolactone in swab samples from Buruli ulcer lesions. Although the described capture ELISA can serve as a tool for research on the biology of mycolactone, the assay system will have to be adapted for use as a diagnostic tool.

Synthesis and Self-Assembly of Double-Hydrophilic and Amphiphilic Block Glycopolymers.

In this report, we present double-hydrophilic block glycopolymers of poly(2-hydroxyethyl methacrylate)-b-poly(2-(β-glucosyloxy)ethyl methacrylate) (PHEMA-b-PGEMA) and amphiphilic block glycopolymers of poly(ethyl methacrylate)-b-PGEMA (PEMA-b-PGEMA) synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization. The block glycopolymers were prepared in two compositions of P(H)EMA macro-chain transfer agents (CTAs) and similar molecular weights of PGEMA. Structural analysis of the resulting polymers as well as the conversion of (H)EMA and GEMA monomers were determined by 1H NMR spectroscopy. Size exclusion chromatography measurements confirmed both P(H)EMA macro-CTAs and block glycopolymers had a low dispersity (Đ ≤ 1.5). The synthesized block glycopolymers had a degree of polymerization and a molecular weight up to 222 and 45.3 kg mol–1, respectively. Both block glycopolymers self-assembled into micellar structures in aqueous solutions as characterized by fluorescence spectroscopy, ultraviolet–visible spectroscopy, and dynamic light scattering experiments.

ЗАКОНОМІРНОСТІ КИСЛОТНОГО ГІДРОЛІЗУ БЛОК-КОПОЛІМЕРІВ, ЩО МІСТЯТЬ ПОЛІАКРИЛАМІД ТА ПОЛІЕТИЛЕНОКСИД

Polymeric micelles self-assembled from amphiphilic block copolymers have been intensively investigated as nano-carrier systems for tumor-targeted drug delivery. Diblock copolymers PEO-b-PAAm (DBC) and thriblock copolymers PAAm-b-PEO-b-PAAm (TBC) contained biocompatible chemically complementary polyacrylamide and poly(ethylene oxide) formed micellar structures in aqueous solutions which have hydrophobic complex “core” formed by the hydrogen-bonded PEO/PAAm chains and hydrophilic “corona” of the surplus segments of PAAm blocks. The ability of DBCs and TBCs to bind the anticancer drug doxorubicin was established. This opened the new prospects for using such copolymers as nanocontainers for toxic and poorly soluble drugs. Successful implementation of DBC and TBC micelles for drug delivery requires the presence a special vectors, particularly galactose, in the micellar “corona”. Such vectors can recognize corresponding receptors on a cellular surface, interact with them, and penetrate into the intracellular space by the endocytosis pathway. In order to introduce the galactose vectors into DBC or TBC micelles, the corona forming PAA blocks have to contain the corresponding active groups, such as –OH, –COO–, –NH2. Therefore, the methods of DBCs (TBCs) functionalization are particularly important since it allows to input the necessary saccharides and also to expand the applications of micellar nanocarriers to encapsulate and delivery of both the drug substances and genetic materials. In the present work, the polymer-analogous conversion of DBCs and TBCs by the acid hydrolysis of PAAm blocks at 50°C was studied. Kinetic investigations of the hydrolysis reaction of DBCs (TBCs) in comparison with pure PAAm were performed by potentiometric titration. It was established that the process of acid hydrolysis of diblock- and thriblock copolymers depends on the blocks length and occurs more intensive in the block copolymers which have longest PEO and PAA chains. The reasons for this phenomenon are discussed. The fact is that hydrolysis of DBCs samples develops efficiently in comparison with TBCs ones attributed to the steric obstacles which appears in TBCs micelles because of their more complicated structure.

Stimuli-responsive properties of special micellar nanocarriers and their application for delivery of vitamin E and its analogues

Stimuli-responsive micelles were formed by asymmetric diblock and triblock copolymers, which comprised chemically complementary (methoxy)poly(ethylene oxide) and poly(acrylic acid) blocks of different length. They were used as nanocarriers to encapsulate and deliver in vivo a poorly soluble homolog of α-tocopheryl acetate (α-TOCAh), commonly known as an analogue of vitamin E. Self-assembly of the copolymer macromolecules into special micellar structures in aqueous solutions depended on the solution pH. The micellar structures arising at pH < 5 due to hydrogen bonds between the blocks and the subsequent segregation of the hydrophobic bound segments in the aqueous medium were stable in the temperature range 20–60 °C and with dilution of the solution. The micelle formation/destruction in the copolymer solutions at pH alteration was shown to be an equilibrium process. Various morphological forms of micelles depending on the copolymer structure and the blocks’ asymmetry were revealed by the TEM method. All types of micelles showed high binding degrees (about 100%) of α-TOCAh, which did not depend on the encapsulation pathway (“in situ” or “ex situ”). Encapsulation of α-TOCAh resulted in hydrophobization of the micelle surface, thereby enhancing the aggregation of micelles in aqueous solution. Encapsulated α-tocopheryl acetate was in vivo fully digested by the animals (white mice) and showed increased biological activity, which allowed reducing its therapeutic dose by 25 times.

Peroxidase chemically attached on polymeric micelle and its reaction with phenolic compounds.

Horseradish peroxidase was chemically modified with comb-shaped polymaleic anhydride-alt-1-tetradecene (PMA-TD) in microemulsion systems to produce surface-active peroxidase that has capability to form micellar structures in aqueous solutions and can be concentrated at liquid/liquid interfaces without unfolding of the enzyme. For chemical modification oil-in-water (O/W) and water-in-oil (W/O) microemulsion systems composed of n-butyl acetate and a buffer solution were prepared because n-butyl acetate turned out to be less detrimental to the activity of peroxidase at high degree of modification compared to other organic solvents. The modification degree of amine groups on the surface of peroxidase by maleic anhydride groups on PMA-TD was reached at equilibrium after 1h reaction at 0°C, and 42% of amine groups were modified with 7-fold amount of PMA-TD to peroxidase (wt/wt). The activity of the PMA-TD-modified peroxidase measured with 2,4-dichlorophenol at pH 7.0 was increased by approximately 2-fold compared to native peroxidase. There was no significant shift in optimum pH after modification, and optimum pH measured with 2,4-dichlorophenol was observed at pH 7.0. For all six phenolic compounds tested, there was a significant increase in the reaction efficiency with the PMA-TD-modified peroxidase. The remarkable enhancement of the reaction efficiency by the modification was presumably because of micellar structures of PMA-TD that could concentrate hydrophobic phenolic oligomers into the core of the micelles. Overall, horseradish peroxidase chemically attached to the surface of PMA-TD micelles was found to be significantly effective for the oxidative polymerization of phenolic compounds.

Self-assembly of well-defined fatty acid based amphiphilic thermoresponsive random copolymers

Side-chain stearic acid containing thermoresponsive and crystalline random copolymers are synthesized via RAFT technique, which self-assembled to spherical micellar structures in aqueous solution depending on stearate content in the copolymer.

Polymeric supra-amphiphiles based on terminal group electrostatic interactions: fabrication of micelles with modifiable surfaces.

On the basis of terminal group electrostatic interactions (TGEI), a supra-amphiphile is formed between a homopolymer of polylactic acid with carboxyl group at one end (PLA-COOH) and hepta-6-hydrazyl-β-cyclodextrin (HH-CD). The amphiphile can self-assemble into a micellar structure in aqueous solution. The outer surface of the micelle, which is composed of cyclodextrins, can be further modified via host-guest interactions. Considering the biocompatibility of the building blocks, the application of the micelles in a nanocarrier of anticancer drugs is further explored.

KillerFLIP: a novel lytic peptide specifically inducing cancer cell death

One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killerFLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using electron microscopy demonstrated that killerFLIP-E triggers cell death accompanied by rapid (within minutes) plasma membrane permeabilization. Studies of the structure of the active core of killerFLIP (-E) indicated that it possesses amphiphilic properties and self-assembles into micellar structures in aqueous solution. The biochemical properties of killerFLIP are comparable to those of cationic lytic peptides, which participate in defense against pathogens and have also demonstrated anticancer properties. We show that the pro-cell death effects of killerFLIP are independent of its sequence similarity with c-FLIPL as killerFLIP-induced cell death was largely apoptosis and necroptosis independent. A killerFLIP-E variant containing a scrambled c-FLIPL motif indeed induced similar cell death, suggesting the importance of the c-FLIPL residues but not of their sequence. Thus, we report the discovery of a promising synthetic peptide with novel anticancer activity in vitro and in vivo.

PH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors

Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (∼7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.

Micellar ordered structure effects on high‐resolution CE‐SSCP using Pluronic triblock copolymer blends

Pluronic F108 block copolymers have shown a great promise to achieve the desirable high resolution in the conformation-sensitive separation of ssDNA using CE-SSCP. However, fundamental understanding of the structures and properties of Pluronic matrix affecting the resolution is still limited. Unlike conventional gel-forming homopolymers, Pluronic F108 block copolymers are amphiphilic macromolecules consisting of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymers, which are capable of forming a highly ordered micellar structure in aqueous solution. In this study, we have performed a series of experiments by blending different types of Pluronic polymers to control the formation of micelles and to study the correlation between separation and rheological characteristics of Pluronic gels affecting the resolution of CE-SSCP. Our experiments have been specifically designed to elucidate how the micellar structure affects the resolution of CE-SSCP upon altering the size uniformity and constituent homogeneity of the micelles. Our results suggest that uniformly sized micelle packing is the primary structural feature of Pluronic gel matrix for the high-resolution separation, while the size and constituent of the micelle themselves need to be considered as secondary factors.

Synthesis and self‐assembly of amphiphilic brush‐dendritic‐linear poly[poly(ethylene glycol) methyl ether methacrylate]‐b‐ polyamidoamine‐b‐poly(ε‐caprolactone) copolymers

AbstractA series of novel amphiphilic brush‐dendritic‐linear poly[poly(ethylene glycol) methyl ether methacrylate]‐b‐polyamidoamine‐b‐poly(ε‐caprolactone) copolymers (PPEGMEMA‐b‐Dm‐b‐PCL) (m = 1, 2, and 3: the generation number of dendron) were synthesized by the combination techniques of click chemistry, atom transfer radical polymerization (ATRP), and ring‐opening polymerization (ROP). The brush‐dendritic copolymers bearing hydrophilic brush PPEGMEMA and hydrophobic dendron polyamidoamine protected by the tert‐butoxycarbonyl (Boc) groups [Dm‐(Boc) (m = 1, 2, and 3)] were for the first time prepared by ATRP of poly(ethylene glycol) methyl ether methacrylate monomer (PEGMEMA) initiated with the dendron initiator, which was prepared from 2′‐azidoethyl‐2‐bromoisobutyrate (AEBIB) and Dm‐(Boc) terminated with a clickable alkyne by click chemistry. Then, the brush‐dendritic copolymers with primary amine groups (PPEGMEMA‐b‐Dm) were obtained from the removal of the protected Boc groups of the brush‐dendritic copolymers in the presence of trifluoroacetic acid. The brush‐dendritic‐linear PPEGMEMA‐b‐Dm‐b‐PCL copolymers were synthesized from ROP of ε‐caprolactone monomer using PPEGMEMA‐b‐Dm as the macroinitiators and stannous octoate as catalyst in toluene at 130 °C. To the best of our knowledge, this is the first report that integrates hydrophilic brush polymer PPEGMEMA with hydrophobic polyamidoamine (PAMAM) dendron and PCL to form amphiphilic brush‐dendritic‐linear copolymers. The amphiphilic brush‐dendritic‐linear copolymers can self‐assemble into spherical micellar structures in aqueous solution. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Synthesis, characterization and micellization of heterograft copolymers based on phosphoester functionalized macromonomers via “grafting through” method

AbstractNovel amphiphilic heterograft copolymers consisting of phosphoester functionalized PEG (phosPEG) and PCL (phosPCL) were synthesized by the ring‐opening polymerization via “grafting through” method. The heterograft structure and thermal properties of these copolymers with various compositions were characterized by 1H‐NMR, 31P NMR, size exclusion chromatography (SEC), and differential scanning calorimetry (DSC) in detail. These amphiphilic copolymers could self‐assemble into micellar structures in aqueous solution, and their critical micellization concentrations (CMC) were determined to be 0.69–1.25 mg/L by fluorescence technique. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements show that these heterograft copolymer micelles are spherical in shape with the particle size ranging from 20 to 60 nm, which has potential in biomedical application. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

A novel dextran-oleate-cRGDfK conjugate for self-assembly of nanodrug

We report a novel synthetic biocompatible material: a conjugate with a fatty acid-substituted dextran decorated with cRGDfK peptide, which was used as a stable coating material instead of the conventional poly(ethylene glycol) for nanodrug preparation. This novel dextran-oleate-cRGDfK conjugate (DO-cRGDfk) could self-assemble into a micellar structure in aqueous solution, and was used as a surfactant to formulate nanodrug with poly(d,l-lactic- co-glycolic) acid as matrix to encapsulate paclitaxel with high drug-loading efficiency. The conjugate allowed the fabrication of nanodrug with a targeting moiety on its surface in a simple and robust step. The resultant nanoparticles could induce cellular apoptosis more effectively than that of the commercial paclitaxel formulation, Taxol. Thus, DO-cRGDfk could be used as an alternative to poly(ethylene glycol) as a biocompatible surface coating polymeric material for nanoparticle preparation. From the Clinical Editor The authors describe a novel synthetic biocompatible conjugate, which consists of a fatty acid-substituted dextran decorated with cRGDfK peptide. This conjugate was used as a stable coating material for nanodrug preparation, and can be used in place of conventional PEG.

Synthesis and morphology transformation of amphiphilic diblock polyurethane copolymers in aqueous solution

Amphiphilic block copolymers possess both hydrophobic and hydrophilic properties and can form versatile micellar structures in aqueous solution. The aim of the research presented was to prepare a series of non-ionic amphiphilic diblock polyurethane copolymers (PUn) based on isophorone diisocyanate, monoallyl-end-capped poly(ethylene oxide) and poly(propylene oxide) (PPO), followed by an investigation of their micellization properties and morphology transformation in aqueous solution. The PUn samples were synthesized by condensation polymerization. These polyurethanes exhibit surface tension as low as 33.7–37.0 mN m−1. There is an obvious decrease in critical micelle concentration as the hydrophobic PPO molecular weight increases. According to transmission electron microscopy, the morphology of aggregates of the copolymers can be tuned by varying the concentration in aqueous solution rather than organic solvent. For example, for PU7, large compound micelles are produced instead of vesicles. For PU17, the concentration can be used to control the size and thickness of vesicles. Vesicle size increases from 60 to 500 nm and vesicle thickness from 40 to 60 nm with concentration ranging from 0.003 to 0.03 wt%. The study shows that the copolymers in aqueous solution have excellent surface activities. In addition, they can self-assemble into large compound micelles or vesicles at certain concentrations. Moreover, the synthesis method described allows one to obtain a desired morphology of aggregates by adjusting the composition of hydrophilic and hydrophobic segments, which provides a novel and simple way to obtain particles on the nanometer scale. Copyright © 2010 Society of Chemical Industry

One-Pot Syntheses of Amphiphilic Centipede-like Brush Copolymers via Combination of Ring-Opening Polymerization and “Click” Chemistry

Amphiphilic centipede-like brush copolymers with biodegradable poly(e-caprolactone) and poly(ethyl ethylene phosphate) side segments were prepared by a one-pot syntheses strategy. The syntheses combined ring-opening polymerization of 2-ethoxy-2-oxo-1,3,2-dioxaphospholane through a “grafting from” strategy and “click” reaction with α-propargyl-ω-acetyl-poly(e-caprolactone) through a “grafting to” strategy, using multifunctional poly(tert-butyl methacrylate)-co-poly(2-hydroxy-3-azidopropyl methacrylate) that bears hydroxyl and azide groups from junction points. The reactions are controllable, and the structure of obtained centipede-like brush copolymer is well characterized. These brush copolymers are amphiphilic and self-assemble into spherical micellar structure in aqueous solution with critical aggregation concentration around 10−3 mg mL−1 and average diameters of 50−90 nm. Such micelles formed from centipede-like brush copolymers can be used as drug carriers for biomedical applications.

Beta-casein nanovehicles for oral delivery of chemotherapeutic drugs

Bovine β-casein (β-CN) is an abundant milk protein that is highly amphiphilic and self-assembles into stable micellar structures in aqueous solutions. Here we introduce a drug-delivery system comprising a model hydrophobic anticancer drug, mitoxantrone (MX), entrapped within β-CN–based nanoparticles. This novel drug-delivery system allows hydrophobic drugs to be thermodynamically stable in aqueous solutions for oral-delivery applications aimed at treatment of various disorders. The gastric digestibility of β-CN suggests possible targeting to stomach tumors. Dimethyl sulfoxide (DMSO)-dissolved MX was entrapped in β-CN nanoparticles by stirring this solution into phosphate-buffered β-CN solution. High-affinity MX–β-CN association was found ( K a = [2.15 ± 0.30] × 10 6 M -1). The optimal nanovehicle formation conditions were 1 mg/mL β-CN, ≤6% (vol/vol) DMSO in phosphate-buffer solution, 10 mM MX in DMSO, and a MX:β-CN molar-ratio of ∼4:1. Under these conditions, particles of 100 to 300-nm diameter were formed. β-CN nanoparticles may serve as effective oral-delivery nanovehicles for solubilization and stabilization of hydrophobic drugs. From the Clinical Editor Bovine β-casein (β-CN) is an abundant milk-protein that is highly amphiphilic and self-assembles into stable micellar-structures in aqueous solutions. β-CN nanoparticles may serve as effective oral-delivery nanovehicles for solubilization and stabilization of hydrophobic drugs, as demonstrated in this study utilizing methotrexate.

Syntheses of amphiphilic biodegradable copolymers of poly(ethyl ethylene phosphate) and poly(3-hydroxybutyrate) for drug delivery

Biodegradable and amphiphilic triblock copolymers poly(ethyl ethylene phosphate)-poly(3-hydroxy-butyrate)-poly(ethyl ethylene phosphate) (PEEP-b-PHB-b-PEEP) have been successfully synthesized through ring-opening polymerization. The structures are confirmed by gel permeation chromatography and NMR analyses. Crystallization investigated by X-ray diffraction reveals that the block copolymer with higher content of poly(ethyl ethylene phosphate) (PEEP) is more amorphous, showing decreased crystallizability. The obtained copolymers self-assemble into biodegradable nanoparticles with a core-shell micellar structure in aqueous solution, verified by the probe-based fluorescence measurements and transmission electronic microscopy (TEM) observation. The hydrophobic poly(3-hydroxybutyrate) (PHB) block serves as the core of the micelles and the micelles are stabilized by the hydrophilic PEEP block. The size and size distribution are related to the compositions of the copolymers. Paclitaxel (PTX) has been encapsulated into the micelles as a model drug and a sustained drug release from the micelles is observed. MTT assay also demonstrates that the block copolymers are biocompatible, rendering these copolymers attractive for drug delivery.

Micellar size, shape and counterion binding of N-(1,1-Dihydroperfluoroalkyl)-N,N,N-trimethylammonium chloride in aqueous solutions

Under the limiting conditions, light-scattering method was applied to determine the size and shape of fluorinated micellar structure in aqueous solution. The hydrodynamic radii (rh) of molecular aggregates were investigated for four amphiphiles with different alkyl chain length: N-(1,1-dihydroperfluorooctyl)-, N-(1,1-dihydroperfluorodecyl)-, N-(1,1-dihydroperfluorododecyl)-, and N-(1,1-dihydroperfluorotetradecyl)-N,N,N-trimethylammonium chloride by dynamic light scattering. Size of these molecular aggregates drastically increased with increasing carbon number of alkyl chain and the concentration. For example, the rh values were 35, 63, 95, and 136 nm for C8, C10, C12, and C14 of the alkyl chain, respectively, at the concentration of 15× critical micelle concentration (cmc) and at 298.2 K. On the other hand, the mean radius of gyration (rg) and the apparent molecular weight of these aggregates were measured using static light scattering. The rg value was found to be 34, 73, and 125 nm for C8, C10, and C12 of the alkyl chain, respectively, at the same condition above. The shape of aggregate was analyzed by comparing the dependence of rg/rh with theoretical values. The plots of rg against rh almost corresponded with the theoretical line of oblate ellipsoid (disk-like), and which was also expected from calculation of packing parameter value. The measurement for chloride ion activity was made by a chloride ion selective electrode to know the degree of counterion binding to the aggregates, whose values increased with increasing total concentration and with the carbon number of alkyl chain. The chloride ion binding to aggregates neutralized cationic head groups under their electrostatic repulsion and partly promoted the growth of aggregates.

Low molecular weight PEI conjugated pluronic copolymer: Useful additive for enhancing gene transfection efficiency

For enhancing the gene delivery efficiency of polyplexes, a new formulation was developed using PEI conjugated Pluronic F127 copolymer as an effective additive. Low molecular weight, branched polyethylenimine Mw 600 (LMW BPEI 600)|was conjugated to the terminal end of Pluronic F127. The PEI-modified Pluronic copolymers formed a micellar structure in aqueous solution, similar to that of unmodified Pluronic copolymer. PEI modification of Pluronic copolymer increased the size of micelles while concomitantly raising the critical micelle concentration (CMC). The PEI-modified Pluronic copolymer was used as a micellar additive to enhance the gene transfection efficiency of pre-formulated polyelectrolyte complex nanoparticles composed of luciferase plasmid DNA and branched PEI Mw 25k (BPEI 25k) or polylysine Mw 39k (PLL 39k). The luciferase gene expression levels were significantly enhanced by the addition of the BPEI-modified Pluronic copolymer for the two formulations of BPEI and PLL polyplexes. The results indicated that the BPEI-modified Pluronic copolymer micelles ionically interacted on the surface of DNA/ BPEI (PLL) polyplexes which might facilitate cellular uptake process.