Synthesis of star‐shaped poly(D,L‐lactic acid‐alt‐glycolic acid)‐b‐poly(L‐lactic acid) with the poly(D,L‐lactic acid‐alt‐glycolic acid) macroinitiator and stannous octoate catalyst

Two types of three‐arm and four‐arm, star‐shaped poly(D,L ‐lactic acid‐alt‐glycolic acid)‐b‐poly(L ‐lactic acid) (D,L ‐PLGA50‐b‐PLLA) were successfully synthesized via the sequential ring‐opening polymerization of D,L ‐3‐methylglycolide (MG) and L ‐lactide (L ‐LA) with a multifunctional initiator, such as trimethylolpropane and pentaerythritol, and stannous octoate (SnOct₂) as a catalyst. Star‐shaped, hydroxy‐terminated poly(D,L ‐lactic acid‐alt‐glycolic acid) (D,L ‐PLGA50) obtained from the polymerization of MG was used as a macroinitiator to initiate the block polymerization of L ‐LA with the SnOct₂ catalyst in bulk at 130 °C. For the polymerization of L ‐LA with the three‐arm, star‐shaped D,L ‐PLGA50 macroinitiator (number‐average molecular weight = 6800) and the SnOct₂ catalyst, the molecular weight of the resulting D,L ‐PLGA50‐b‐PLLA polymer linearly increased from 12,600 to 27,400 with the increasing molar ratio (1:1 to 3:1) of L ‐LA to MG, and the molecular weight distribution was rather narrow (weight‐average molecular weight/number‐average molecular weight = 1.09–1.15). The ¹H NMR spectrum of the D,L ‐PLGA50‐b‐PLLA block copolymer showed that the molecular weight and unit composition of the block copolymer were controlled by the molar ratio of L ‐LA to the macroinitiator. The ¹³C NMR spectrum of the block copolymer clearly showed its diblock structures, that is, D,L ‐PLGA50 as the first block and poly(L ‐lactic acid) as the second block. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 409–415, 2002     

Synthesis and characterization of poly(N‐(2‐mercaptoethyl) acrylamide) microgel for biomedical applications

N‐(2‐mercaptoethyl) acrylamide (MEAM) monomer was synthesized by acrylation of cysteamine and was cross‐linked with ethylene glycol dimethacrylate (EGDMA) via dispersion polymerization forming poly(N‐(2‐mercaptoethyl) acrylamide) (p(MEAM)) microgel. Then, the prepared microgels were tested for potential biomedical use, eg, antioxidant capacity and blood compatibility, cytotoxicity, apoptotic, and necrotic cell death; drug delivery properties were determined. Antioxidant studies of p(MEAM) microgels revealed a super antioxidant capability with total phenol content and trolox equivalent antioxidant capacity as 6.05 ± 1.15 mg/L gallic acid equivalency and 40.96 ± 2.40 mM trolox/g, respectively. Moreover, the blood compatibility of p(MEAM) microgels on fresh blood was resulted in lower than 1.0% hemolysis ratios for all the studied concentration range, and the blood clotting index was determined as 60.66% at 2.0 mg/mL at microgel concentration. The biocompatibility studies employing WST‐1 test on L929 fibroblast cells and DLD‐1 colon cancer cells have shown that p(MEAM) microgel was biocompatible up to 200 μg/mL concentration with the cell viability values of 84.54% and 86.15% on L929 fibroblast and DLD‐1 colon cancer cells, respectively. Using Captopril was used as model drug to test p(MEAM) microgel as drug delivery device for in vitro release studies at different pHs. Release profile of Captopril was found linear up to 5 hours with the released amounts of 9.81, 12.24, and 13.78 mg g^‐1microgel at the pH 1.5, 7.4, and 9.0, respectively.     

Synthesis of poly(D,L‐lactic acid‐alt‐glycolic acid) from D,L‐3‐methylglycolide

D ,L ‐3‐Methylglycolide (MG) was synthesized via two step reactions with a good yield (42%). It was successfully polymerized in bulk with stannous octoate as a catalyst at 110 °C. The effects of the polymerization time and catalyst concentration on the molecular weight and monomer conversion were studied. Poly(D ,L ‐lactic acid‐co‐glycolic acid) (D ,L ‐PLGA50; 50/50 mol/mol) copolymers were successfully synthesized from the homopolymerization of MG with high polymerization rates and high monomer conversions under moderate polymerization conditions. ¹H NMR spectroscopy indicated that the bulk ring‐opening polymerization of MG conformed to the coordination–insertion mechanism. ¹³C NMR spectra of D ,L ‐PLGA50 copolymers obtained under different experimental conditions revealed that the copolymers had alternating structures of lactyl and glycolyl. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4179–4184, 2000     

Gas‐forming poly(ethylene glycol)‐b‐poly(L‐lactic acid) micelles

In this study, a novel drug‐carrying micelle composed of methoxy poly(ethylene glycol) (mPEG)‐b‐poly(L‐lactic acid) (PLLA) with gas‐forming carbonate linkage was fabricated. Here, the gas‐forming carbonate linkage was formed by the chemical coupling of the terminal hydroxyl group of the PLLA block and benzyl chloroformate (BC). mPEG‐b‐PLLA‐BC was self‐organized in aqueous solution: the PEG block on the hydrophilic outer shell and the PLLA‐BC block in the hydrophoboic innor core. The cleavage of carbonate linkage by hydrolysis and formation of carbon dioxide nanobubbles in the micellar core enabled an accelerated release of the encapsulated anticancer drug (doxorubicin: DOX) from the mPEG‐b‐PLLA‐BC micelles. The amount of drug (DOX) released from the mPEG‐b‐PLLA‐BC micelle was higher than that from the conventional mPEG‐b‐PLLA micelle, which allowed for increased in vitro toxicity against KB tumor cells. Copyright © 2013 John Wiley & Sons, Ltd.     

Cancer‐associated pH‐responsive tetracopolymeric micelles composed of poly(ethylene glycol)‐b‐poly(L‐histidine)‐b‐poly(L‐lactic acid)‐b‐poly(ethylene glycol)

To create a novel vector for specifically delivering anticancer therapy to solid tumors, we used diafiltration to synthesize pH‐sensitive polymeric micelles. The micelles, formed from a tetrablock copolymer [poly(ethylene glycol)‐b‐poly(L ‐histidine)‐b‐poly(L ‐lactic acid)‐b‐poly(ethylene glycol)] consisted of a hydrophobic poly(L ‐histidine) (polyHis) and poly(L ‐lactic acid) (PLA) core and a hydrophilic poly(ethylene glycol) (PEG) shell, in which we encapsulated the model anticancer drug doxorubicin (DOX). The robust micelles exhibited a critical micellar concentration (CMC) of 2.1–3.5 µg/ml and an average size of 65–80 nm pH 7.4. Importantly, they showed a pH‐dependent micellar destabilization, due to the concurrent ionization of the polyHis and the rigidity of the PLA in the micellar core. In particular, the molecular weight of PLA block affected the ionization of the micellar core. Depending on the molecular weight of the PLA block, the micelles triggering released DOX at pH 6.8 (i.e. cancer acidic pH) or pH 6.4 (i.e. endosomal pH), making this system a useful tool for specifically treating solid cancers or delivering cytoplasmic cargo in vivo. Copyright © 2008 John Wiley & Sons, Ltd.     

Structural Characterization and Degradability of Poly(L‐lactic acid)s Incorporating Phenyl‐Substituted α‐Hydroxy Acids as Comonomers

Three types of copolymers of poly(L ‐lactic acid) (PLLA) were synthesized by direct polycondensation of L ‐lactic acid and phenyl‐substituted α‐hydroxy acids (L ‐phenyllactic acid and D ‐ and L ‐mandelic acids). It was found that the glass transition temperature of the copolymers comprising L ‐mandelic acid became significantly higher (from 58 to 69 °C) with increasing content of L ‐mandelic acid (from 0 to 50 mol‐%) although the M _w decreased (from 87 000 to 4 000 Da). The cast films of the L ‐mandelic acid containing copolymers showed improved tensile properties compared with those of the PLLA film. This may be due to a pinning effect of the L ‐mandelic acid units on the helix formation of PLLA, although 30% of the units were racemized. The enzymatic degradability of the L ‐mandelic acid containing copolymers was much higher than that of PLLA, as analyzed with Proteinase K® originating from Tritirachium album.

Synthesis of copolymers of L ‐lactic acid and phenyl‐substituted α‐hydroxy acids.     

Novel L‐DOPA‐Derived Poly(ester amide)s: Monomers,Polymers, and the First L‐DOPA‐Functionalized Biobased Adhesive Tape

The synthesis, characterization, and testing of a range of novel bio‐inspired L‐DOPA‐derived poly(ester amide)s is presented, using a widely applicable, straightforward chemistry. A model system is used to study and establish the monomer and polymer synthetic protocols, and to provide a set of optimum reaction conditions. It is further shown that fully biobased L‐DOPA‐containing adhesive tapes can be fabricated, which are positively evaluated in terms of their adhesive properties. The newly developed synthetic protocol constitutes a versatile platform for accessing and tailoring a plethora of relevant structures, including a variety of potentially biocompatible poly(ethylene glycol)‐based materials.

     

Lipo‐Poly(L‐histidine) Hybrid Materials with pH‐Sensitivity,Intracellular Delivery Efficiency,and Intrinsic Targetability to Cancer Cells

Biocompatible lipo‐histidine hybrid materials conjugated with IR820 dye show pH‐sensitivity, efficient intracellular delivery of doxorubicin (Dox), and intrinsic targetability to cancer cells. These new materials form highly uniform Dox‐loaded nanosized vesicles via a self‐assembly process showing good stability under physiological conditions. The Dox‐loaded micelles are effective for suppressing MCF‐7 tumors, as demonstrated in vitro and in vivo. The combined mechanisms of the EPR effect, active internalization, endosomal‐triggered release, and drug escape from endosomes, and a long blood circulation time, clearly prove that the IR820 lipopeptide DDS is a safe theranostic agent for imaging‐guided cancer therapy.

     

Methoxypoly(ethylene glycol)‐block‐Poly(L‐glutamic acid)‐Loaded Cisplatin and a Combination With iRGD for the Treatment of Non‐Small‐Cell Lung Cancers

CDDP is loaded into methoxypoly(ethylene glycol)‐block‐poly(L ‐glutamic acid) (mPEG‐b‐PLG), and a combination with iRGD is applied for NSCLC chemotherapy. The CDDP‐loaded micelles show sustained cisplatin release in PBS, dose‐ and time‐dependent inhibition to HeLa and A549 cell proliferation, and no apparent hemolysis activities. In in vivo studies using subcutaneous NSCLC xenograft models (A549), both free CDDP and CDDP‐loaded micelles show an evident anti‐tumor effect. However, the toxicity of CDDP is significantly reduced in the cases of CDDP‐loaded micelles and co‐administration with iRGD, and the survival time is prolonged by over 30%. Therefore, mPEG‐b‐PLG‐loaded cisplatin and the combination with iRGD provides a promising new therapy for NSCLC.

     

Carboxymethyl poly(L‐histidine) as a new pH‐sensitive polypeptide at endosomal/lysosomal pH

A carboxymethyl poly(L ‐histidine) has been synthesized as a new pH‐sensitive polypeptide at endosomal/lysosomal pH. Because of its poor water solubility at physiological pH, an application of poly(L ‐histidine) with a pK_a around 6.0 has been limited in spite of the native possession of the pH‐dependent property change at endosomal pH. Although the unmodified poly(L ‐histidine) suddenly precipitates out of the aqueous medium above pH 6.0 as the result of the deprotonation of the imidazole groups, the water solubility of the resulting carboxymethyl poly(L ‐histidine) has been improved at physiological pH. A solution turbidity measurement proved that no significant effect on a rapid aggregate formation or phase separation of serum proteins is induced by carboxymethyl poly(L ‐histidine). Hemolysis assay showed that the carboxymethyl poly(L ‐histidine) enhances membrane disruptive ability at endosomal/lysosomal pH. The cellular uptake of luciferase in the presence of the carboxymethyl poly(L ‐histidine) increases intracellular luciferase activity, which suggests that the carboxymethyl poly(L ‐histidine) makes the luciferase escape from lysosomal degradation. The carboxymethyl poly(L ‐histidine) would be the fundamental compound for designing various drug carriers with the pH sensitivity at endosomal/lysosomal pH. Copyright © 2007 John Wiley & Sons, Ltd.     

Poly(p‐phenylene) with Poly(ethylene glycol) Chains and Amino Groups as a Functional Platform for Controlled Drug Release and Radiotherapy

Conventional cancer treatments such as chemotherapy, radiotherapy, or combination of these two result in side effects, which lower the quality of life of the patients. To overcome problems with these methods, altering the drug properties by conjugating them to carrier polymers has emerged. Such polymeric carriers also hold the potential to make tumor cells more sensitive to radiation therapy. Herein, poly(p‐phenylene) (PPP) polymer with poly(ethylene glycol) (PEG) chains and primary amino groups (PPP‐NH₂‐g‐PEG) is synthesized and conjugated with anticancer drug Doxorubicin (DOX). pH dependent drug release experiments are performed at pH 5.3 and pH 7.4, respectively. Cell viability studies on human cervix adenocarcinoma cells show that lower doses of DOX inhibit cell proliferation when conjugated with nontoxic doses of PPP‐NH₂‐g‐PEG polymer. Additionally, PPP‐NH₂‐g‐PEG/Cys/DOX bioconjugate significantly increases radiosensitive properties of DOX. It is possible to use lower doses of DOX when conjugated to PPP‐NH₂‐g‐PEG in combination with radiotherapy.

     

Investigation on thermoresponsive behavior of biodegradable poly(γ‐glutamic acid)‐graft‐L‐phenylalanine ethyl ester

The thermosensitivity of biodegradable and non‐toxic amphiphilic polymer derived from a naturally occurring polypeptide and a derivative of amino acid was first reported. The amphiphilic polymer consisted of poly(γ‐glutamic acid) (γ‐PGA) as a hydrophilic backbone, and L ‐phenylalanine ethyl ester (L ‐PAE) as a hydrophobic branch. Poly(γ‐glutamic acid)‐graft‐L ‐phenylalanine (γ‐PGA‐graft‐L ‐PAE) with grafting degrees of 7–49% were prepared by varying the content of a water‐soluble carbodiimide (WSC). γ‐PGA‐graft‐L ‐PAE with a grafting degree of 49% exhibited thermoresponsive phase transition behavior in an aqueous solution at around 80°C. The copolymers with grafting degrees in the range of 30–49% showed thermoresponsive properties in NaCl solution. A clouding temperature (T_cloud) could be adjusted by changing the polymer concentration and/or NaCl concentration. The thermoresponsive behavior was reversible. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Poly(styrene‐co‐glycerol dimethacrylate): Synthesis,characterization, and application as a resin for gel‐phase peptide synthesis

An efficient cross‐linked polymer support for solid‐phase synthesis was prepared by introducing glycerol dimethacrylate cross‐linker to polystyrene network using free radical aqueous suspension polymerization. The support was characterized by various spectroscopic methods. Morphological feature of the resin was analyzed by microscopy. The polymerization reaction was investigated with respect to the effect of amount of cross‐linking agent, which in turn vary the swelling, loading, and the mechanical stability of the resin. The solvent uptake of the polymer was studied in relation to cross‐linking and compared with Merrifield resin. The stability of the resin was tested in different synthetic conditions used for solid‐phase peptide synthesis. Hydroxy group of the support was derivatized to chloro and then amino groups using different reagents and reaction conditions. Efficiency of the support was tested and compared with TentaGel? resin by following different steps involved in the synthesis of the 65–74 fragment of acyl carrier protein. The results showed that the poly(styrene‐co‐glycerol dimethacrylate) (GDMA‐PS) is equally efficient as TentaGel resin in peptide synthesis. The purity of the peptides was analyzed by HPLC and identities were determined by mass spectroscopy and amino acid analysis. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4382–4392, 2005     

New Preparation of Structurally Symmetric,Biodegradable Poly(L‐lactide) Disulfides and PLLA–Stabilized,Photoluminescent CdSe Quantum Dots

New, biodegradable poly(L ‐lactide) disulfides, PLLA‐SS‐PLLA, were first prepared through the DMAP‐catalyzed ring‐opening polymerization of L ‐lactide with a dihydroxyethyl disulfide initiator, and were further catalytically reduced into thiol‐end‐functionalized poly(L ‐lactide)s, HO‐PLLA‐SH, with a tributyl phosphine catalyst (PBu₃). Employing the HO‐PLLA‐SH as the ligand, new core‐shell CdSe/PLLA quantum dots (QDs) were continuously prepared via a facile ligand‐exchanging process with the CdSe/TOPO QD precursor. The chemical structures, morphologies and solvent solubility of these prepared CdSe/PLLA QDs were investigated by NMR spectroscopy, FTIR spectroscopy, XRD, TEM and excitation under either room light or UV radiation at 365 nm, demonstrating the successful ligand replacement and the new formation of core‐shell CdSe/PLLA QDs (diameter:4.0 ± 0.3 nm). Finally, UV and FL results indicate the two factors of the HO‐PLLA‐SH ligand molecular weight and the ligand/QD precursor feeding weight ratio were important for preparing stable and highly photoluminescent CdSe/PLLA QDs.

     

Paclitaxel‐Loaded Stabilizer‐Free Poly(D,L‐lactide‐co‐glycolide) Nanoparticles Conjugated with Quantum Dots for Reversion of Anti‐Cancer Drug Resistance and Cancer Cellular Imaging

We prepared the PLGA‐loaded anti‐cancer drug and coated it with quantum dots to make it a dual‐function nanoparticles, and analyzed its potential use in cellular imaging and curing cancers. Two cancer cell lines, paclitaxel‐sensitive KB and paclitaxel‐resistant KB paclitaxel‐50 cervical carcinoma cells, were the relativistic models for analysis of the cytotoxicity of free paclitaxel and paclitaxel‐loaded PLGA conjugated with quantum‐dot nanoparticles. The paclitaxel‐loaded PLGA conjugated with quantum dots nanoparticles were significantly more cytotoxic than the free paclitaxel drug in paclitaxel‐resistant KB paclitaxel‐50 cells. This might have been because the cancer cells developed multi‐drug resistance (MDR), which hampered the action of free paclitaxel by pumping its molecules to extracellular areas. Addition of verapamil, a P‐glycoprotein inhibitor, reversed the MDR mechanism and significantly reduced KB paclitaxel‐50 cell viability. As a result, KB paclitaxel‐50 was highly associated with MDR on the cell membrane. The cytotoxicity results indicated that PLGA nanoparticles served as drug carriers and protected the drugs from MDR‐accelerated efflux. Combined quantum dots with PLGA nanoparticles allowed additional functionality for cellular imaging.     

Poly(ethylene terephthalate) copolyesters derived from (2S,3S)‐2,3‐dimethoxy‐1,4‐butanediol

Novel poly(ethylene terephthalate) (PET) copolyesters, abbreviated PEDMBT, containing optically active (2S,3S)‐2,3‐dimethoxy‐1,4‐butanediol (DMBD) as the second comonomer were investigated. Copolymers with ethylene glycol to DMBD ratios between 95/5 and 50/50 as well as the two parent homopolymers, PET and PDMBT, were prepared by a two‐step melt polycondensation. The resulting copolymers were found to approximately have the composition of the polymerization reaction feed and a random microstructure. Polymer intrinsic viscosities varied from 0.4 to 0.6 dL g^?1 with weight‐average molecular weights ranging from 16,000 to 44,000. PEDMBT copolyesters were distinguished in being much more soluble than PET and showing an increasing affinity for water with the content in dimethoxy groups. According to the asymmetric constitution of DMBD, they displayed optical activity in solution. Both melting and glass‐transition temperatures of the copolyesters were observed to steadily decrease with the content in DMBD. PEDMBTs were found to be crystalline for contents in DMBD up to 30 mol %. Both powder and fiber X‐ray diffraction revealed that the same crystalline structure is shared by PET and the crystalline copolyesters. The homopolyester PDMBT resulted in becoming a polymer with a crystallinity comparable to PET but with a significantly different crystalline structure. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3250–3262, 2001     

Synthesis and characterization of novel thermoresponsive‐co‐biodegradable hydrogels composed of N‐isopropylacrylamide,poly(L‐lactic acid), and dextran

A series of novel multifunctional hydrogels that combined the merits of both thermoresponsive and biodegradable polymeric materials were designed, synthesized, and characterized. The hydrogels were copolymeric networks composed of N‐isopropylacrylamide (NIPAAM) as a thermoresponsive component, poly(L‐lactic acid) (PLLA) as a hydrolytically degradable and hydrophobic component, and dextran as an enzymatically degradable and hydrophilic component. The chemical structures of the hydrogels were characterized by an attenuated total reflection–Fourier transform infrared spectroscopy (ATR–FTIR) technique. The hydrogels were thermoresponsive, showing a lower critical solution temperature (LCST) at approximately 32 °C, and their swelling properties strongly depended on temperature changes, the balance of the hydrophilic/hydrophobic components, and the degradation of the PLLA component. The degradation of the hydrogels caused by hydrolytic cleavage of ester bonds in the PLLA component was faster at 25 °C below the LCST than at 37 °C above the LCST, determined by the ATR–FTIR technique. Due to their multifunctional properties, the designed hydrogels show great potential for biomedical applications, including drug delivery and tissue engineering. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5054–5066, 2004     

Synthesis,characterization, and physical properties of new copolymers of poly(amino acid)–urethane—copolymers of γ‐methyl‐L‐glutamate‐N‐carboxyanhydride and urethane prepolymer

New copolymers of amino acid and urethane (PAU), in which a polyurethane segment was combined with poly(γ‐methyl‐L‐glutamate) (PMLG) of various contents, were synthesized by the copolymerization of the polyurethane prepolymer (UPP) having isocyanate groups at both terminals of the chain and γ‐methyl‐L ‐glutamate‐N‐carboxyanhydride (NCA) to improve the elastic recovery and adhesion of PMLG for application of PMLG to synthetic leather. The copolymerization of the UPP with NCA was carried out by applying the reactivity of isocyanate and the polymerization mechanism of NCA using the primary amine and tertiary amine as initiators. Infrared (IR) and ¹³C‐NMR spectra of these PAUs as well as the chemical analysis of the PAU intermediates showed that the PAUs would have a multiblock–triblock structure: namely, the PAUs consisted of the block copolymer segments of urethane and a small amount of PMLG at the center of the copolymer chain and most of the PMLG at both terminals of the copolymer chain. The elastic recovery and adhesion of these PAUs were significantly larger than those of the PMLG with the maintenance of a good sense of touch, which was a unique asset of PMLG. Furthermore, it was found that the PAUs had intermediary moisture permeability between that of PMLG and polyurethane. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 383–389, 1999     

Impact of Cationic Charge Density and PEGylated Poly(amino acid) Tercopolymer Architecture on Their Use as Gene Delivery Vehicles. Part 1: Synthesis,Self‐Assembly,and DNA Complexation

The interaction of PEGylated poly(amino acid)s with their biological targets depends on their chemical nature and spatial arrangement of their building blocks. The synthesis, self‐assembly, and DNA complexation of ABC terblock copolymers consisting of poly(ethylene glycol), (PEG), poly(l ‐lysine), and poly(l ‐leucine), are reported. Block copolymers are produced by a metal‐free, living ring‐opening polymerization of respective amino acid N‐carboxyanhydrides using amino‐terminated PEG as macroinitiator: (PEG‐b‐p(l ‐Lys)_x‐b‐p(l ‐Leu)_y, PEG‐b‐p(l ‐Leu)_x‐b‐p(l ‐Lys)_y, and PEG‐b‐p((l ‐Lys)_x‐co‐p(l ‐Leu)_y). Sizes of self‐assembled nanoparticles depend on the formation method. The nanoprecipitation method proves useful for copolymers with the poly(l ‐lysine) block protected as trifluoroacetate, effective diameters range between 92 and 132 nm, while direct dissolution in distilled water is suitable for the deprotected copolymers, yielding effective diameters between 52 and 173 nm. Critical micelle concentration (CMC) analyses corroborate particle size analyses and show a distinct impact of the molecular architecture; the lowest CMC (8 µg mL⁻¹) is observed when the poly(l ‐leucine) segment forms the C‐block and the hydrophilic, disassembly driving poly(l ‐lysine) segment is short. DNA complexation, evaluated by gel motility and RiboGreen analyses, depends strongly on the molecular architecture. A more efficient DNA complexation is observed when poly(l ‐lysine) and poly(l ‐leucine) form individual blocks as opposed to them forming a copolymer.