Cationic Polymeric Micelles Research Articles

Direct synthesis of Poly(Ԑ-Caprolactone)-block-poly (glycidyl methacrylate) copolymer and its usage as a potential nano micelles carrier for hydrophobic drugs

Ring-opening (ROP) and enzymatic copolymerization (ECP) are among the most widely used approaches for synthesizing copolymers of polycaprolactone (PCL). It involves multiple-step reactions and the utilization of enzymes that make the process a lot more complicated, time consuming, and expensive. Atom transfer radical polymerization (ATRP) has been adopted to synthesize a novel amphiphilic copolymer in our study. The study presents a method to eliminate the ROP/ECP multiple steps in monomer polymerization thus making the process simpler and smoother. The synthesis of cationic polymer micelles copolymer of PCL-PGMA (polycaprolactone grafted poly glycidyl methacrylate) was carried out using direct functionalization of hydroxy group in crude PCL to achieve a higher degree of functionalization, i.e., 12.8% for macroinitiator. FTIR and 1H-NMR confirmed the successful synthesis of the copolymer with better control over the molecular weight with a PDI (1.84). DSC and XRD results showed the reduction of crystallinity by 86.81%, making copolymer more compatible for drug delivery application. The synthesized copolymer was further converted to nano-micelles drug carrier having an average size of 96.08 ± 21.22 nm. The drug encapsulation efficiency achieved was 60.0 ± 1.7%, and nano-micelles rendered a slow and controlled release of naproxen with long-term storage stability.

Co‐delivery of paclitaxel and CXCL1 shRNA via cationic polymeric micelles for synergistic therapy against ovarian cancer

AbstractThe preparation of polymer therapeutics capable of synergistic co‐delivery systems for chemotherapeutic drugs and genes remains a tough problem in cancer therapy. Herein, we develop a novel co‐delivery system for chemotherapeutic drugs and genes. Paclitaxel (PTX) was covalently grafted onto the cationic copolymer poly(ethylene glycol)‐b‐poly(l‐lysine) (PEG‐b‐PLL) via a disulfide bond, and then CXCL1 shRNA was loaded on the cationic micelles PEG‐b‐PLL‐SS‐PTX by electrostatic interaction to construct PEG‐b‐PLL‐SS‐PTX/pDNA complex. The chemical structure of the complex was confirmed by gel permeation chromatography, 1H NMR and Fourier transform infrared spectroscopy. The binding ability of the cationic micelles and pDNA was detected by gel retardation assay. In vitro gene transfection studies revealed an enhanced gene transfection efficiency due to the co‐delivery of PTX and pDNA to ovarian cancer cells. In vitro and in vivo data demonstrated that the co‐delivery complex exhibited a synergistic role of chemotherapy and gene therapy and possessed enhanced antitumor effects. The strategy of using drug‐loaded cationic micelles as gene delivery carriers is a versatile approach to construct a co‐delivery system, which might result in more efficient cancer therapy. © 2022 Society of Industrial Chemistry.

Construction of mannose-modified polyethyleneimine-block-polycaprolactone cationic polymer micelles and its application in acute lung injury.

This study evaluated the D-mannose modified polyethyleneimine-block-polycaprolactone biomacromolecule copolymer micelles (PCL-PEI-mannose) as a targeted delivery of the glucocorticoid dexamethasone (DXM) to lung inflammation tissues and enhances the vehicle for its anti-inflammatory effects. Dexamethasone was encapsulated in the hydrophobic core of cationic polymer micelles by solvent evaporation. The polymeric micelles exhibited sustained-release within 48h, good blood compatibility, and colloidal stability in vitro. The cellular uptake of mannose-modified micelles was higher compared with the non-modified micelles. And drug-loaded targeted micelles could inhibit the production of inflammatory factors in activated RAW264.7 cells. The distribution results indicated that drug-loaded targeted micelles highly improved the lung targeting ability, reduced the wet/dry ratio of injured lung tissue, and relieved the lung inflammation, accompanied by the decrease of inflammatory cell infiltration, myeloperoxidase activity, and inflammatory mediator levels in bronchoalveolar lavage fluid. These findings suggested that PCL-PEI-mannose delivery system could facilitate the lung-specific delivery and inhibit the inflammatory response. Collectively, PCL-PEI-mannose polymer micelles could be used as a potential delivery system for the treatment of acute lung injury (ALI).

Destruction of Pseudomonas aeruginosa pre-formed biofilms by cationic polymer micelles bearing silver nanoparticles

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen often associated with biofilm infections. This study evaluated the capacity for biofilm destruction of a novel combination of cationic polymer micelles formed from poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA-PCL-PDMAEMA) triblock copolymer either alone, or loaded with silver nanoparticles (M_AgNPs). Pre-formed P. aeruginosa biofilms were incubated with either blank micelles, AgNO3, or M_AgNPs. Biofilm biomass (crystal violet assay), metabolic activity (Alamar blue reduction), structure (SEM) and viability (CLSM after Live/Dead staining, or plating for CFU) were checked. The results showed that the micelles alone loosened the biofilm matrix, and caused some alterations in the bacterial surface. AgNO3 killed the bacteria in situ leaving dead biofilm bacteria on the surface. M_AgNPs combined the two types of activities causing significant biofilm reduction, and alteration and death of biofilm bacteria. Therefore, the applied PDMAEMA-based micelles appear to be a successful candidate for the treatment of P. aeruginosa biofilm infections.

Redox-Responsive Efficient DNA and Drug Co-Release from Micelleplexes Formed from a Fluorescent Cationic Amphiphilic Polymer.

Cationic polymeric micelles that are capable of co-releasing drugs and DNA into cells have attracted considerable interest as combination chemotherapy in cancer treatment. To this effect, we have presently developed a cationic fluorescent amphiphilic copolymer, poly(N,N'-dimethylaminoethylmethacrylate)-b-(poly(2-(methacryloyl)oxyethyl-2'-hydroxyethyl disulfidecholate)-r-2-(methacryloyloxy)ethyl-1-pyrenebutyrate) [PDMAEMA-b-(PMAODCA-r-PPBA)], having pendent cholate moiety linked through a redox-responsive disulfide bond. The amphiphilic nature of the copolymer facilitated the formation of cationic micellar nanoparticles in aqueous medium. The self-assembly of the copolymer to form micelles and subsequent destabilization of the micelles in the presence of glutathione (GSH) was monitored by the change in the fluorescence characteristic of the attached pyrene resulting from alteration in the hydrophobicity of its neighborhood. These micellar nanoparticles were subsequently utilized in encapsulating hydrophobic anticancer drug, doxorubicin (DOX), in the core of the micelles, whereas the cationic shell of the micelles was used for complexation with oppositely charged DNA to form micelleplexes. Gel retardation assays, ethidium bromide (EB) exclusion assay, and DLS and AFM studies confirmed the successful binding of the cationic micelles with DNA. The binding capability of the micelles was higher than corresponding cationic linear PDMAEMA. The kinetics of the simultaneous release of encapsulated DOX and complexed DNA in the presence of glutathione was thoroughly studied using various techniques. All the experiments showed fast and efficient release of DOX and DNA from DOX-loaded micelleplexes. The study implies that these redox-responsive cationic micelles may open up new opportunities toward co-delivery of DNA and anticancer drugs in combinatorial therapy.

Smart pH-responsive polymeric micelles for programmed oral delivery of insulin

The development of intelligent oral drug delivery carrier aiming at efficiently bring insulin to intestine is of great significance for diabetes mellitus therapy. In the present study, a series of amphiphilic pH-sensitive block copolymer poly(methyl methacrylate-co-methacrylicacid)-b-poly(2-amino ethyl methacrylate) [P(MMA-co-MAA)-b-PAEMA] was synthesized via activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and further self-assembled into pH-responsive cationic polymeric micelles (PCPMs) for oral insulin delivery. The structure and molecular weight were confirmed by proton nuclear magnetic resonance (1H-NMR), Fourier transforming infrared spectrum (FT-IR) and gel permeation chromatography (GPC), respectively. The critical micelle concentration (CMC) values of these copolymers were measured by fluorescent probe method at pH 1.2 (8–15 μg/mL) and pH 7.4 (22–42 μg/mL), respectively, demonstrating high stability at acidic environment. A decrease in the particle size of PCPMs was associated with an increased pH at beginning, which reached around 200 nm at neutral pH, while the particle size increased obviously with pH increase, indicating the pH-sensitivity of PCPMs. The insulin was entrapped into the core of PCPMs (Ins-loaded PCPMs) with high loading efficiency via diafiltration method. The in vitro experiments show Ins-loaded PCPMs have low toxicity and exhibit pH-triggered release profile with remitted initial burst release. The results indicate that the PCPMs self-assembled from P(MMA-co-MAA)-b-PAEMA may be potential carriers for efficient oral delivery of insulin with controlled release property.

Albumin-Modified Cationic Nanocarriers To Potentially Create a New Platform for Drug Delivery Systems.

Cationic nanocarriers have emerged as promising nanoparticle systems for the effective delivery of nucleic acid and anticancer drugs to cancer cells. A positive charge is desirable for promoting cell internalization, whereas it also causes some adverse effects, such as toxicity and rapid clearance by mononuclear phagocytic systems. Herein, a new strategy of modifying cationic polymer micelles with albumin forming a protein corona to improve the surface physiochemical properties is reported. The corona with a monolayer or a multilayer was constructed depending on the albumin concentration, and the proteins would denature in different degrees due to the interaction with the surface of cationic micelles. It is demonstrated that multilayer albumin corona is beneficial to prevent macrophage uptake, increase accumulation in tumor tissues, and reduce toxic side effects to normal tissues. Our work provides a promising method to modify the cationic nanoplatform by optimizing the biosecurity and bioavailability for potential application in drug delivery.

Application of cationic polymer micelles for the dispersal of bacterial biofilms.

Contamination of surfaces in hospitals and food industry by bacterial biofilms is a serious health risk. Of concern is their resistance to routine antibacterials and disinfectants. This requires the development of novel approaches to biofilm detachment. The study evaluates the effectiveness of cationic polymer micelles (CPMs) against pre-formed biofilms. CPMs based on different polycations were used. The hydrodynamic radius of the particles ranged from 16 to 360 nm. Biofilms of Escherichia coli 420, Pseudomonas aeruginosa PAO1, Staphylococcus aureus 29213 and Bacillus subtilis 168 were cultivated for 24 h then the pre-formed biofilms were treated with the CPMs for 2, 4 or 6 h. Biofilm biomass was evaluated by the crystal violet assay, and live/dead fluorescence test was applied for bacterial viability. The ability of CPMs to interact with pre-formed biofilms of the model strains was evaluated. We observed that the most effective CPMs were those based on poly(2-(dimethylamino)ethyl methacrylate) copolymers which reduced the biofilm biomass three- to four-fold compared with the treatment of the biofilm with water. Significantly reduced vitality of the bacteria in the biofilms was registered by the live/dead stain. The results indicate the applicability of the CPMs for disinfection of biofilm-contaminated surfaces and the treatment of wounds.

Synthesis and evaluation of cationic polymeric micelles as carriers of lumbrokinase for targeted thrombolysis

To achieve targeted thrombolysis, a targeted delivery system of lumbrokinase (LK) was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GPⅡb/Ⅲa expressed on the surface of membrane of activated platelet, LK loaded targeted micelles (LKTM) can be delivered to thrombus. The hybrid micelles were composed of polycaprolactone-block-poly (2-(dimethylamino) ethyl methacrylate) (PCL-PDMAEMA), methoxy polyethylene glycol-block- polycaprolactone (mPEG-PCL) and RGDfk conjugated polycaprolactone-block- polyethylene glycol (PCL-PEG-RGDfk). PCL-PDMAEMA was synthesized via ring open polymerization (ROP) and atom transfer radical polymerization (ATRP). PCL-PEG-RGDfk was synthesized via ROP and carbodiimide chemistry. The prepared LKTM was characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Colloidal stability assay showed the prepared LKTM was stable. Biocompatibility assay was performed to determine the safe concentration range of polymer. The assay of fluorescent distribution in vivo demonstrated that LKTM can be efficiently delivered to thrombi in vivo. Thrombolysis in vivo indicated the thrombolytic potency of LKTM was optimal in all groups. Notably, the laboratory mice treated with LKTM exhibited a significantly shorter tail bleeding time compared to those treated with LK or LK-loaded micelles without RGDfk, which suggested that the targeted delivery of LK using RGDfk-conjugated hybrid micelles effectively reduced the bleeding risk.

Elaboration on the Distribution of Hydrophobic Segments in the Chains of Amphiphilic Cationic Polymers for Small Interfering RNA Delivery.

Hydrophobization of cationic polymers, as an efficient strategy, had been widely developed in the structure of cationic polymer micelles to improve the delivery efficiency of nucleic acids. However, the distribution of hydrophobic segments in the polymer chains is rarely considered. Here, we have elaborated three types of hydrophobized polyethylene glycol (PEG)-blocked cationic polymers with different distributions of the hydrophobic segments in the polymer chains PEG-PAM-PDP (E-A-D), PEG-PDP-PAM (E-D-A), and PEG-P(AM/DP) (E-(A/D)), which were synthesized by reversible addition-fragmentation chain transfer polymerization of methoxy PEG, cationic monomer aminoethyl methacrylate, and pH-sensitive hydrophobic monomer 2-diisopropylaminoethyl methacrylate, respectively. In aqueous solution, all of the three copolymers, E-A-D, E-D-A, and E-(A/D), were able to spontaneously form nanosized micelles (100-150 nm) (ME-A-D, ME-D-A, and ME-(A/D)) and well-incorporated small interfering RNA (siRNA) into complex micelles (CMs). The effect of distributions of the hydrophobic segments on siRNA delivery had been evaluated in vitro and in vivo. Compared with ME-D-A and ME-(A/D), ME-A-D showed the best siRNA binding capacity to form stable ME-A-D/siRNA CMs less than 100 nm, mediated the best gene-silencing efficiency and inhibition effect of tumor cell growth in vitro, and showed better liver gene-silencing effect in vivo. In the case of ME-(A/D) with a random distribution of cationic and hydrophobic segments, a gene-silencing efficiency higher than Lipo2000 but lesser than ME-A-D and ME-D-A was obtained. As the mole ratio of positive and negative charges increased, ME-D-A/siRNA and ME-A-D/siRNA showed similar performances in size, zeta potential, cell uptake, and gene silencing, but ME-(A/D)/siRNA showed reversed performances. In addition, ME-A-D as the best siRNA carrier was evaluated in the tumor tissue in the xenograft murine model and showed good anticancer capacity. Obviously, the distribution of the hydrophobic segments in the amphiphilic cationic polymer chains should be seriously considered in the design of siRNA vectors.

A novel polymeric micelle used for in vivo MR imaging tracking of neural stem cells in acute ischemic stroke

Novel cationic polymeric micelles based on biodegradable poly(aspartic acid-dimethylethanediamine)–lysine–cholic acid were synthesized for in vivo tracking therapeutic stem cells using MRI.

Design of polycationic micelles by self‐assembly of polyethyleneimine functionalized oligo[(ε‐caprolactone)‐co‐glycolide] ABA block copolymers

Cationic polymeric micelles are of interest as delivery materials for nucleotides allowing condensation and transport of anionic macromolecules and enabling the reduction of cytotoxicity of polyethyleneimine, the current standard of vectors for non‐viral nucleic acid delivery. In addition, micelles based on a degradable core would be capable to degrade hydrolytically and release their payload, which should preferably occur after uptake in early endosomes providing a pH of 5.5. We explored whether degradable and amphiphilic ABA block copolymers from hyperbranched polyethyleneimine A blocks and B blocks based on hydrophobic oligoesters (CG) can be created, which can degrade in a pH range relevant for the early endosomes. CG was synthesized by ring‐opening polymerization of ε‐caprolactone and diglycolide. Polycationic micelles with particle sizes between 19 ± 1 and 43 ± 2 nm were obtained by self‐assembly of the ABA block copolymers with different chain lengths of B blocks and/or co‐assembly with a diblock copolymer from poly(ethylene glycol) (PEG) functionalized CG oligoester in phosphate‐buffered saline solution. Mixed micelles containing PEG‐CG showed a decreased zeta potential, suggesting a shielding by dangling PEG chains at the micelle surfaces. Sizes of cationic micelles were stable at pH = 7.4 over the studied time period of 2 weeks at 37 °C. The hydrolytic degradation was controlled by the composition of the CG core and was accelerated when the pH was decreased to 5.5 as detected by increasing micelle sizes. In this way, the polycationic micelles may act as an on‐demand delivery system of condensed macromolecules. Copyright © 2016 John Wiley & Sons, Ltd.

Reduction-Degradable Polymeric Micelles Decorated with PArg for Improving Anticancer Drug Delivery Efficacy.

In this study, five kinds of reduction-degradable polyamide amine-g-polyethylene glycol/polyarginine (PAA-g-PEG/PArg) micelles with different proportions of hydrophilic and hydrophobic segments were synthesized as novel drug delivery vehicles. Polyarginine not only acted as a hydrophilic segment but also possessed a cell-penetrating function to carry out a rapid transduction into target cells. Polyamide amine-g-polyethylene glycol (PAA-g-PEG) was prepared for comparison. The characterization and antitumor effect of the DOX-incorporated PAA-g-PEG/PArg cationic polymeric micelles were investigated in vitro and in vivo. The cytotoxicity experiments demonstrated that the PAA-g-PEG/PArg micelles have good biocompatibility. Compared with DOX-incorporated PAA-g-PEG micelles, the DOX-incorporated PAA-g-PEG/PArg micelles were more efficiently internalized into human hepatocellular carcinoma (HepG2) cells and more rapidly released DOX into the cytoplasm to inhibit cell proliferation. In the 4T1-bearing nude mouse tumor models, the DOX-incorporated PAA-g-PEG/PArg micelles could efficiently accumulate in the tumor site and had a longer accumulation time and more significant aggregation concentration than those of PAA-g-PEG micelles. Meanwhile, it excellently inhibited the solid tumor growth and extended the survival period of the tumor-bearing Balb/c mice. These results could be attributed to their appropriate nanosize and the cell-penetrating peculiarity of polyarginine as a surface layer. The PAA-g-PEG/PArg polymeric micelles as a safe and high efficiency drug delivery system were expected to be a promising delivery carrier that targeted hydrophobic chemotherapy drugs to tumors and significantly enhanced antitumor effects.

Click modified amphiphilic graft copolymeric micelles of poly(styrene-alt-maleic anhydride) for combinatorial delivery of doxorubicin and plk-1 siRNA in cancer therapy.

The anti-apoptotic defense mechanism of cancer cells poses a major hurdle which makes chemotherapy less effective. Combinatorial delivery of drugs and siRNAs targeting anti-apoptotic proteins is a vital means for improving therapeutic effects. The present study aims at designing a suitable carrier which can effectively co-deliver doxorubicin and plk1 siRNA to tumor cells. Low molecular weight poly(styrene-alt-maleic anhydride) was chemically modified via a click reaction to obtain a cationic amphiphilic polymer for the co-delivery of therapeutic agents. Short glycol chains were utilized as linker molecules for grafting which in turn imparted a stealth nature and minimized plasma protein adsorption to the polymeric surface. Isonicotinic acid was grafted to the polymer due to its ability to penetrate the endolysosomal membrane and arginine-lysine conjugates were embedded for complexing siRNA. The polymer was able to self-assemble in to smooth, spherical micellar structures with a CMC of ∼3 μg mL-1. The particle size of the micelles was ∼14-30 nm as depicted using TEM and FESEM. Atomic force microscopic analysis showed an average height of ∼12 nm for the polymeric micelles. An optimum doxorubicin loading of ∼9% w/w was achieved with the micelles using a dialysis method. Effective complexation of siRNA occurred above a polymer/siRNA weight ratio of 10 without any significant change in the particle size. Doxorubicin and fluorescent labeled siRNA loaded micelles exhibited excellent co-localization within the cytoplasm of MCF-7 cells. The synergistic effect of the active agents in inhibiting tumor cell proliferation was depicted using an MTT assay and visualized using calcein/propidium iodide staining of the treated cells. Co-administration of doxorubicin and plk1 siRNA in EAT tumor bearing Swiss albino mice using the cationic micelles significantly enhanced the antitumor efficacy.

Cationic triblock copolymer micelles enhance antioxidant activity, intracellular uptake and cytotoxicity of curcumin

The aim of the present study was to develop curcumin loaded cationic polymeric micelles and to evaluate their loading, preservation of curcumin antioxidant activity and intracellular uptake ability. The micelles were prepared from a triblock copolymer consisting of poly(ϵ-caprolactone) and very short poly(2-(dimethylamino) ethyl methacrylate) segments (PDMAEMA9–PCL70–PDMAEMA9). The micelles showed monomodal size distribution, mean diameter of 145nm, positive charge (+72mV), critical micellar concentration around 0.05g/l and encapsulation efficiency of 87%. The ability of the micellar curcumin to scavenge the ABTS radical and hypochlorite ions was higher than that of the free curcumin. Confocal microscopy revealed that the uptake of curcumin by chronic myeloid leukemia derived K-562 cells and human multiple myeloma cells U-266 was more intensive when curcumin was loaded into the micelles. These results correlated with the higher cytotoxicity of the micellar curcumin compared to free curcumin. Intraperitoneal treatment of Wistar rats indicated that PDMAEMA–PCL–PDMAEMA copolymer, comprising very short cationic chains, did not change the levels of malondialdehyde and glutathione in livers indicating an absence of oxidative stress. Thus, PDMAEMA–PCL–PDMAEMA triblock micelles could be considered efficient and safe platform for curcumin delivery.

Paclitaxel-conjugated PEG and arginine-grafted bioreducible poly (disulfide amine) micelles for co-delivery of drug and gene

We developed a paclitaxel-conjugated polymeric micelle, ABP-PEG3.5k-Paclitaxel (APP) consisting of poly (ethylene glycol) (PEG) and arginine-grafted poly (cystaminebisacrylamide-diaminohexane) (ABP) for the co-delivery of gene and drug. The APP polymer self-assembled into cationic polymeric micelles with a critical micelle concentration (CMC) value of approximately 0.062 mg/mL, which was determined from measurements of the UV absorption of pyrene. The micelles have an average size of about 3 nm and a zeta potential of about +14 mV. Due to the positive surface charge, APP micelles formed polyplexes with plasmid DNA approximately 200 nm in diameter. The luciferase gene and mouse interleukin-12 (IL-12) gene was used to monitor gene delivery potency. APP polyplexes showed increased gene delivery efficiency and cellular uptake with higher anticancer potency than paclitaxel alone. These results demonstrate that an APP micelle-based delivery system is well suitable for the co-delivery of gene and drug.

DNA encapsulation via nanotemplates from cationic block copolymer micelles

We report on a method for the encapsulation of DNA into polymeric nanocapsules. The encapsulation procedure involves three steps: formation of polyplexes between DNA and cationic polymeric micelles; coating of polyplexes with a cross-linked shell; dissociation of polyplexes. In the first step copolymer micelles were obtained by self-assembly of an amphiphilic polystyrene-b-poly(quaternized 2-vinylpyridine) (PS-b-PQ2VP) block copolymer in aqueous solution. Nanosized polyplexes (Dh = 190 nm and ζ = −21 mV) were formed upon the addition of DNA to the micellar solution at a phosphate/amine group ratio of 3 : 1. In the second step the complexes were coated with a cross-linked shell formed by seeded radical polymerization of N-isopropylacrylamide which resulted in a slight shift of ζ potential of the particles to a less negative value. The dissociation of polyplexes and removal of PS-b-PQ2VP were achieved by addition of salt and solvent exchange. Following rehydration viadialysis against water, polymeric nanocapsules with entrapped DNA were obtained. The nanocapsules were visualized by transmission electron microscopy; they exhibited smaller dimensions compared to the initial polyplexes and ζ potential very close to that of the pristine DNA.

Synergistic Anticancer Effects Achieved by Co‐Delivery of TRAIL and Paclitaxel Using Cationic Polymeric Micelles

Cationic micellar nanoparticles self-assembled from a biodegradable amphiphilic copolymer have been used to deliver human TRAIL and paclitaxel simultaneously. Polyplexes formed between paclitaxel-loaded nanoparticles and TRAIL are stable with a size of ≈180 nm and a zeta potential at ≈75 mV. Anticancer effects and apoptotic pathway mechanisms of this drug-and-protein co-delivery system are investigated in various human breast cancer cell lines with different TRAIL sensitivity. The co-delivery nanoparticulate system induces synergistic anti-cancer activities with limited toxicity in non-cancerous cells. An advantage of this co-delivery is a significantly higher anti-cancer effect as compared to free drug and protein formulations.

Stearic acid grafted chitosan oligosaccharide micelle as a promising vector for gene delivery system: Factors affecting the complexation

Stearic acid (SA) grafted chitosan oligosaccharide (CSO-SA) with different molecular weight of chitosan oligosaccharide (CSO) and graft ratio of stearic acid were synthesized by coupling reaction of SA and CSO. The cationic polymeric micelles of CSO-SA via self-assemble formed and used for gene delivery of fish sperm DNA. Factors affecting complexation and stability of the complexes of CSO-SA micelles and DNA were investigated. The results indicated that pKa of CSO-SA with 3 kDa of CSO decreased from 8.16 to 6.02 as the substitution degree of amino groups of CSO in CSO-SA increased from 9.79% to 63.41%, whereas the molecular weight ( M W) of CSO less affected the pKa. As for the stability of complexes, ethidium bromide assay data demonstrated that the complexes consisting of CSO-SA with lower amino substitution degree or smaller molecular weight of CSO were more stable than that with the higher amino substitution degree or molecular weight of CSO. The results also presented that the low pH and ionic strength environment were in favor for the stability of complexes.

Complexes of Cationic Block Copolymer Micelles with DNA: Histone/DNA Complex Mimetics

The formation of complexes between cationic polymeric micelles of PS-b-PQ2VP amphiphilic block copolymers and DNA molecules in aqueous solutions is investigated at pH = 7. The physicochemical characteristics of the "polyplexes" at different DNA/polymer ratios were characterized in terms of mass, size and charge using static, dynamic and electrophoretic light scattering and AFM. The complexes are spherical and assume their maximum size and mass around the charge stoichiometric ratio. After addition of increased amounts of salt in the solutions, partial dissociation of the systems was observed. The present systems can be considered as mimetics of histone/DNA complexes formed under physiological conditions in living cells.