Amphiphilic Triblock Copolymer Research Articles

Neutral Block Copolymer Assisted Gene Delivery using Hydrodynamic Limb Vein Injection.

Three different amphiphilic block copolymer families are synthesized to investigate new opportunities to enhance gene delivery via Hydrodynamic Limb Vein (HLV) injections. First a polyoxazoline-based family containing mostly one poly(2-methyl-2-oxazoline) (PMeOx) block and a second block POx with an ethyl (EtOx), isopropyl (iPrOx) or phenyl substituent (PhOx) is synthesized. Then an ABC poly(2-ethyl-2-oxazoline)-b-poly(2-n-propyl-2-oxazoline)-b-poly(2-methyl-2-oxazoline) triblock copolymer is synthesized, with a thermosensitive middle block. Finally, polyglycidol-b-polybutylenoxide-b-polyglycidol copolymers with various molar masses and amphiphilic balance are produced. The simple architecture of neutral amphiphilic triblock copolymer is not sufficient to obtain enhanced in vivo gene transfection. Double or triple amphiphilic neutral block copolymers are improving the in vivo transfection performances through HLV administration as far as a block having an lower critical solution temperature is incorporated in the vector. The molar mass of the copolymer does not seem to affect the vector performances in a significant manner.

Abstract 5572: Microneedle-guided lymphatic delivery of a natural immune modulator toxin for enhanced cancer immunotherapy

Abstract Cancer immunotherapy has demonstrated significant potential as a cancer treatment by enhancing the immune system's ability to recognize and eliminate cancer cells. However, its efficacy can be limited by factors such as tumor heterogeneity, immunosuppressive tumor microenvironments, and systemic toxicities. Recent advances in drug delivery systems have facilitated the development of more targeted and personalized cancer therapies. Microneedles have emerged as a promising platform for non-invasive and highly localized drug delivery, directly administering drugs, vaccines, and other therapeutic agents to the skin. In this study, we designed dissolving microneedles (dMN) based on a biocompatible amphiphilic tri-block copolymer, which enables the self-assembly of nano-micelles containing hydrophobic drugs when applied to the skin. We used the dMN technology to formulate SKKU-06, a hydrophobic natural immune modulator toxin derived from fungi, which exhibits anti-cancer and immunomodulatory properties in melanoma (SKKU-06@dMN). After intratumoral application of SSKU-06@dMN to skin tumors, the drug-loaded nano-micelles can migrate to tumor-draining lymph nodes (TDLN). The dMN-guided delivery of SKKU-06 to skin tumors and TDLN induced immunogenic cell death and stimulated the activation and maturation of antigen-presenting cells (APCs), promoting the development of humoral and cellular anti-tumor immunity. Furthermore, the immunomodulatory effects of SSKU-06@dMN were enhanced when combined with anti-PD-1 treatment, impacting the tumor microenvironment through increased intratumoral CD8+ T cell infiltration and reduced Treg populations. This resulted in efficient growth inhibition of established skin cancer and metastatic cancer, as well as prolonged survival. The dMN-guided lymphatic delivery of SKKU-06 demonstrates the potential for treating metastatic solid tumors and improving cancer immunotherapy efficacy by modulating the tumor microenvironment. Citation Format: Su Yeon Lim, Byung Deok Kim, PIN LIU, Ju hwa Shin, Ji Hoon Jeong. Microneedle-guided lymphatic delivery of a natural immune modulator toxin for enhanced cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5572.

Stabilizing Zn Anodes by Molecular Interface Engineering with Amphiphilic Triblock Copolymer

Stabilizing Zn Anodes by Molecular Interface Engineering with Amphiphilic Triblock Copolymer

Biodegradable flexible conductive film based on sliver nanowires and PLA electrospun fibers

AbstractBiodegradable conductive films are crucial for the sustainable development of wearable electronics. In this work, a flexible and degradable conductive film was prepared based on a carefully designed interface of polylactic acid (PLA) electrospun fibers and silver nanowires (AgNWs). The amphiphilic triblock copolymer was added to PLA solution for electrospinning, followed by solvent posttreatment to induce the hydrophilic block of the amphiphilic triblock copolymer to migrate to the fiber surface. Dopamine can be uniformly polymerized on the surface of hydrophilic PLA fibers, and the prepared PLA@PDA fiber film can form a good interface combination with AgNWs. The electrical conductivity of AgNWs/PLA@PDA flexible film can reach 258.5 S cm−1, showing obvious Joule heating effect and good mechanical properties. Degradation experiments showed that in phosphate buffered saline, the PLA molecular chain showed a dynamic equilibrium due to the scission and rearrangement of the ester groups and degraded slowly, while AgNWs/PLA@PDA degraded rapidly under alkaline conditions. Our study provides a simple and controllable method to prepare flexible degradable electronic films, which is expected to be applied to flexible wearable bioelectrodes.

Ursolic acid loaded tri-block copolymer nanoparticles based on triphenylphosphine for mitochondria-targeted cancer therapy

A novel biodegradable amphiphilic triblock copolymer, polyphosphate, polyethylene glycol, and polylactic acid (PAEEP-PEG-PLLA), was synthesized by twice ring-opening polymerization and triphenylphosphine (TPP) was grafted onto the block copolymer to synthesize a carrier material TPP-PAEEP-PEG-PLLA, which was identified by 1H-nuclear magnetic resonance (1H-NMR) spectroscopy. The TPP-PAEEP-PEG-PLLA nanoparticles encapsulated with ursolic acid (UA) were prepared by the emulsion-solvent evaporation method and characterized by dynamic light scattering. The mitochondrial targeting ability of fluorescently labeled nanoparticles was evaluated by laser confocal microscopy. The average particle size and surface charge of the UA -loaded nanoparticle solution were 180.07 ± 1.67 nm and +15.57 ± 1.33 mV, respectively. The biocompatibility of nanoparticles was briefly evaluated by erythrocyte hemolysis assay. In vitro cell proliferation assay and scratch migration assay were performed to compare the difference in anti-tumor effect between UA and UA nanoparticles. The results showed that TPP-modified triblock copolymers had good mitochondrial targeting and improved the low bioavailability of UA, and UA nanoparticles exhibited more pronounced anti-tumor capabilities. In summary, the results suggested that our UA nanoparticles were a promising drug-targeted delivery system for the treatment of tumors.

Development of Injectable Thermosensitive Nanocomposite Hydrogel for Ratiometric Drug Delivery to Treat Drug Resistant Chondrosarcoma In Vivo.

Chondrosarcoma(CS), a prevalent primary malignant bone tumor, frequently exhibits chemotherapy resistance attributed to upregulated anti-apoptosis pathways such as the Bcl-2 family. In this manuscript, a new strategy is presented to augment chemosensitivity and mitigate systemic toxicity by harnessing a nano-enabled drug delivery hydrogel platform. The platform utilizes "PLGA-PEG-PLGA", an amphiphilic triblock copolymer combining hydrophilic polyethylene glycol (PEG) and hydrophobic polylactide glycolide (PLGA) blocks, renowned for its properties conducive to crafting a biodegradable, temperature-sensitive hydrogel. This platform is tailored to encapsulate a ratiometrically designed dual-loaded liposomes containing a first-line chemo option for CS, Doxorubicin (Dox), plus a calculated amount of small molecule inhibitor for anti-apoptotic Bcl-2 pathway, ABT-737. In vitro and in vivo evaluations demonstrate successful Bcl-2 suppression, resulting in the restoration of Dox sensitivity, evident through impeded tumor growth and amplified necrosis rates at the tumor site. This delivery system showcases remarkable thermal responsiveness, injectability, and biodegradability, all finely aligned with the clinical demands of CS treatment. Collectively, this study introduces a transformative avenue for tackling drug resistance in CS chemotherapy, offering significant clinical potential.

Co-assembly of Amphiphilic Triblock Copolymers with Nanodrugs and Drug Release Kinetics in Solution.

Polymeric vesicles present great potential in disease treatment as they can be featured as a structurally stable and easily functionalized drug carrier that can simultaneously encapsulate multiple drugs and release them on-demand. Based on the dissipative particle dynamics (DPD) simulation, the drug-loaded vesicles were designed by the co-assembly process of linear amphiphilic triblock copolymers and hydrophobic nanodrugs in solvents, and most importantly, the drug release behavior of drug-loaded vesicles were intensively investigated. The drug-loaded aggregates, such as vesicles, spherical micelles, and disk-like micelles, were observed by varying the size and concentration of nanodrugs and the length of the hydrophobic block. The distribution of nanodrugs in the vesicles was intensively analyzed. As the size of the nanodrugs increases, the localization of nanodrugs change from being unable to fully wrap in the vesicle wall to the uniform distribution and finally to the aggregation in the vesicles at the fixed concentration of nanodrugs. The membrane thickness of the drug-loaded polymeric vesicle can be increased, and the nanodrugs localized closer to the center of the vesicle by increasing the length of the hydrophobic block. The nanodrugs will be released from vesicles by varying the interactions between the nanodrug and the solvent or the hydrophobic block and the solvent, respectively. We found that the release kinetics conforms to the first-order kinetic model, which can be used to fit the cumulative release rate of nanodrugs over time. The results showed that increasing the size of nanodrugs, the length of hydrophobic block, and the interaction parameters between the hydrophobic block and the solvent will slow down the release rate of the nanodrug and change the drug release process from monophasic to biphasic release model.

Ionic Strength Effect in the Equilibrium and Rheological Behavior of an Amphiphilic Triblock Copolymer at the Air/Solution Interface

This study investigates the effect of an inert salt (NaCl) on the equilibrium interfacial tension and dilatational modulus of Pluronic F-68 copolymer, a triblock copolymer consisting of two terminal blocks of poly(ethylene oxide) and a less hydrophilic central block of poly(propylene oxide). Interfacial tension measurements were carried out using a surface force balance and a drop shape tensiometer, while rheological measurements were carried out in two different frequency ranges. This involved the use of the oscillatory barrier/droplet method and electrocapillary wave measurements, complemented by an appropriate theoretical framework. This work aimed to elucidate the influence of NaCl on the interfacial behavior of Gibbs monolayers of Pluronic F-68. In addition, this study highlights some of the technical and theoretical limitations associated with obtaining reliable dilatational rheological data at high frequencies (<1 kHz) using electrocapillary wave measurements. The results provide valuable insights into the interplay between salt presence and interfacial properties of Pluronic F-68 and highlight the challenges of obtaining accurate dilatational rheological data under specific measurement conditions.

Polymer-Drug Conjugates Codeliver a Temozolomide Intermediate and Nitric Oxide for Enhanced Chemotherapy against Glioblastoma Multiforme.

Polymer-drug conjugates (PDCs) provide possibilities for the development of multiresponsive drug delivery and release platforms utilized in cancer therapy. The delivery of Temozolomide (TMZ, a DNA methylation agent) by PDCs has been developed to improve TMZ stability under physiological conditions for the treatment of glioblastoma multiforme (GBM); however, with inefficient chemotherapeutic efficacy. In this work, we synthesized an amphiphilic triblock copolymer (P1-SNO) with four pendant functionalities, including (1) a TMZ intermediate (named MTIC) as a prodrug moiety, (2) a disulfide bond as a redox-responsive trigger to cage MTIC, (3) S-nitrosothiol as a light/heat-responsive donor of nitric oxide (NO), and (4) a poly(ethylene glycol) chain to enable self-assembly in aqueous media. P1-SNO was demonstrated to liberate MTIC in the presence of reduced glutathione and release gaseous NO upon exposure to light or heat. The in vitro results revealed a synergistic effect of released MTIC and NO on both TMZ-sensitive and TMZ-resistant GBM cells. The environment-responsive PDC system for codelivery of MTIC and NO is promising to overcome the efficacy issue in TMZ-based cancer therapy.

Controlling the function of bioactive worm micelles by enzyme-cleavable non-covalent inter-assembly cross-linking

Drugs that form self-assembled supramolecular structures to be most-active is a promising way of creating new highly specific and active pharmaceuticals. Controlling the activity of bioactive supramolecular structures such as drug-loaded micelles is possible by both core/shell and inter-assembly cross-linking. However, if the flexibility of the assembly is mandatory for the activity cross-linking is not feasible. Thus, such structures cannot be manipulated in their activity.The present study demonstrates a novel concept to control the activity of not drug-releasing, non-cross-linked bioactive superstructures. This is achieved by formation of nanostructured nanoparticles derived by non-covalent inter-assembly cross-linking of the superstructures. This is shown on the example of amphiphilic diblock-copolymers conjugated with the antibiotic ciprofloxacin (CIP). These polymer-antibiotic conjugates form worm micelles, which greatly activate the conjugated antibiotic without releasing it. Non-covalent inter-assembly cross-linking of these CIP-worm-micelles with amphiphilic triblock copolymers terminated with lipase-cleavable esters leads to nanostructured nanoparticles that resemble cross-linked worm micelles and show an up to 135-fold lower activity than the free worm micelles. The activity of the worm-micelles can be fully recovered by cleaving the end groups of the polymeric cross-linker with lipase.

An Adaptable Drug Delivery System Facilitates Peripheral Nerve Repair by Remodeling the Microenvironment.

The multifaceted process of nerve regeneration following damage remains a significant clinical issue, due to the lack of a favorable regenerative microenvironment and insufficient endogenous biochemical signaling. However, the current nerve grafts have limitations in functionality, as they require a greater capacity to effectively regulate the intricate microenvironment associated with nerve regeneration. In this regard, we proposed the construction of a functional artificial scaffold based on a "two-pronged" approach. The whole system was developed by encapsulating Tazarotene within nanomicelles formed through self-assembly of reactive oxygen species (ROS)-responsive amphiphilic triblock copolymer, all of which were further loaded into a thermosensitive injectable hydrogel. Notably, the hydrogel exhibits obvious temperature sensitivity at a concentration of 6 wt %, and the nanoparticles possess concentration-dependent H2O2-response capability with a controlled release profile in 48 h. The combined strategy promoted the repair of injured peripheral nerves, attributed to the dual role of the materials, which mainly involved providing structural support, modulating the immune microenvironment, and enhancing angiogenesis. Overall, this study opens up intriguing prospects in tissue engineering.

Amphiphilic pH-responsive ABC triblock copolymers via RAFT-mediated aqueous PISA and comparison with their A-b-(B-co-C) diblock copolymer counterparts

The influence of the macroRAFT agent architecture on the morphology of the self-assemblies obtained by aqueous RAFT dispersion polymerization in PISA is studied by comparing amphiphilic AC, A(B-co-C) diblocks and ABC triblock copolymers, constituted of N,N-dimethylacrylamide (DMAm = A), acrylic acid (AA = B) and N-cyanomethylacrylamide (CMAm = C) monomer units. The aim of this study is to better understand the impact of the presence of pH-sensitive acrylic acid units and their spatial distribution in block copolymers. Generally, the presence of a fully protonated intermediate block of PAA between the two blocks (based on PDMAm and PCMAm) favors the formation of higher-order morphologies. These ABC triblock copolymers assemblies are pH-responsive and can undergo morphological transitions through the controlled deprotonation or protonation of the PAA segment, but do not completely dissociate at high pH (i.e. when AA units are fully ionized) unlike their A(B-co-C) diblock counterparts, where the pH-responsive monomer unit is homogeneously distributed within the solvophobic block.

Gelation upon the Mixing of Amphiphilic Graft and Triblock Copolymers Containing Enantiomeric Polylactide Segments through Stereocomplex Formation.

Biodegradable injectable polymer (IP) systems that form hydrogels in situ when injected into the body have considerable potential as medical materials. In this paper, we report a new two-solution mixed biodegradable IP system that utilizes the stereocomplex (SC) formation of poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA). We synthesized triblock copolymers of PLLA and poly(ethylene glycol), PLLA-b-PEG-b-PLLA (tri-L), and a graft copolymer of dextran (Dex) attached to a PDLA-b-PEG diblock copolymer, Dex-g-(PDLA-b-PEG) (gb-D). We found that a hydrogel can be obtained by mixing gb-D solution and tri-L solution via SC formation. Although it is already known that graft copolymers attached to enantiomeric PLLA and PDLA chains can form an SC hydrogel upon mixing, we revealed that hydrogels can also be formed by a combination of graft and triblock copolymers. In this system (graft vs. triblock), the gelation time was shorter, within 1 min, and the physical strength of the resulting hydrogel (G' > 100 Pa) was higher than when graft copolymers were mixed. Triblock copolymers form micelles (16 nm in diameter) in aqueous solutions and hydrophobic drugs can be easily encapsulated in micelles. In contrast, graft copolymers have the advantage that their molecular weight can be set high, contributing to improved mechanical strength of the obtained hydrogel. Various biologically active polymers can be used as the main chains of graft copolymers, and chemical modification using the remaining functional side chain groups is also easy. Therefore, the developed mixing system with a graft vs. triblock combination can be applied to medical materials as a highly convenient, physically cross-linked IP system.

Preparation of light‐responsive block copolymer modified cellulose nanocrystal@polydopamine particle and its application in fluorinated polyacrylate film

AbstractLight‐responsive cellulose nanocrystal@polydopamine (CNC@PDA) modified fluorinated polyacrylate was synthesized by Pickering emulsion polymerization with light‐responsive block copolymer modified CNC@PDA as stabilizer. The epoxy groups in poly(acrylic acid‐co‐acrylamide)‐b‐poly(glycidyl methacrylate)‐b‐poly(hexafluorobutyl acrylate‐co‐coumarin) amphiphilic triblock copolymer reacted with the hydroxyl and amino groups on the surface of CNC@PDA to form the modified CNC@PDA. The successful preparation of modified CNC@PDA was confirmed by means of FT‐IR, XRD, TG, UV–Vis, surface tension measurement, and X‐ray photoelectron spectroscopy (XPS) techniques. The results showed that the modified CNC@PDA had light‐responsive and amphiphilic properties, and could be used as stabilizer to form stable Pickering emulsion. And the influence of modified CNC@PDA dosage on emulsion polymerization and film performance was systematically studied. The latex particle size decreased initially with increasing modified CNC@PDA dosage, from 0.6 to 1.0 wt%, and then increased. The mechanical, self‐healing, and water–oil repellent properties of film were enhanced initially with increasing modified CNC@PDA dosage, from 0.6 to 1.0 wt%, and then declined. Atomic force microscope confirmed that the latex film had a rough surface. Moreover, the latex film comprising 1.0 wt% modified CNC@PDA presented not only high tensile strength (4.92 MPa), large elongation at break (657.70%), and superior oil/water repellency but also excellent self‐healing property.

Influence of hydrophilic block length on the aggregation properties of polyglycidol-polystyrene-polyglycidol copolymers.

Amphiphilic triblock copolymers, polyglycidol-polystyrene-polyglycidol (PGL-PS-PGL), were synthesised via anionic polymerization starting from the synthesis of a polystyrene macroinitiator with 60 styrene units in the block terminated by ethylene oxide. Poly(ethoxyethyl glycidyl ether) blocks of different lengths were created on both sides of the macroinitiator. By removing the ethoxyethyl blocking groups, PGL-PS-PGL copolymers containing polyglycidol blocks with DP 11, 23, 44 and 63 were received. Their structures were determined by NMR and FTIR. The hydrophilicity of PLG-PS-PGL films was studied upon exposure to water vapour. To perform the copolymers' aggregation in water, the samples were dialysed from DMF into water. The critical concentration of their micellisation (CMC) was determined by measuring the absorbance of the 1,6-diphenylhexa-1,3,5-triene (DPH) probe and the intensity of light scattered by the copolymers' solution as a function of concentration. CMC values increased with increasing the number of hydrophilic glycidol units in the copolymer chain. The sizes of aggregates formed slightly above the critical concentration were measured by dynamic light scattering (DLS), and particles were imaged by cryo-TEM. Cryo-TEM pictures showed the presence of regular micelles in copolymer dispersions. For copolymers with shorter PGL chains aggregated partices were detected. Moreover, cryo-TEM demonstrated that the copolymers with a polyglycidol block of DP = 63 formed regular spherical micelles that formed 2D ordered organisation on the surface. X-ray measurements showed the formation of a partially crystallised PS core in the micelle's interior. The aggregates of all copolymers were stable. Their sizes did not change after one year of storage. The particles did not disassociate even after diluting their dispersions to a concentration 10 times lower than the critical concentration.

PH-controlled breakup of fractal aggregates, microgels and gels formed by self-assembled amphiphilic triblock copolymers.

The degradation of (micro)gels and fractal aggregates based on self-assembled amphiphilic triblock copolymers has been investigated in water by confocal microscopy and light scattering respectively. The triblock copolymer consisted of a central hydrophilic poly(acrylic acid) (pAA) block and two hydrophobic end blocks that contained an equal amount of randomly distributed n-butyl acrylate (nBA) and AA units. These latter units helped at tempering the hydrophobic end blocks resulting in the control and the fine tuning of the dynamics of the self-assembled triblock through the pH. Starting from a pH where the dynamics is frozen, the rate of breakup of the macroscopic gels, microgels and of fractal aggregates was measured after increasing the pH to different values. The mechanism of the breakup was found to be independent of the pH, but its rate increased exponentially with increasing pH. The degradation proceeded through the release of the polymers from the bulk into the surrounding aqueous phase.

Application of Nanohybrid Substrates with Layer-by-Layer Self-Assembling Properties to High-Sensitivity Surface-Enhanced Raman Scattering Detection.

The present study was conducted to prepare and investigate large-area, high-sensitivity surface-enhanced Raman scattering (SERS) substrates. Organic/inorganic nanohybrid dispersants consisting of an amphiphilic triblock copolymer (hereafter referred to simply as "copolymer") and graphene oxide (GO) were used to stabilize the growth and size of gold nanoparticles (AuNPs). Ion-dipole forces were present between the AuNPs and copolymer dispersants, while the hydrogen bonds between GO and the copolymer prevented the aggregation of GO, thereby stabilizing the AuNP/GO nanohybrids. Transmission electron microscopy (TEM) revealed that the AuNPs had particle sizes of 25-35 nm and a relatively uniform size distribution. The AuNP/GO nanohybrids were deposited onto the glass substrate by using the solution drop-casting method and employed for SERS detection. The self-assembling properties of two-dimensional sheet-like GO led to a regular lamellar arrangement of AuNP/GO nanohybrids, which could be used for the preparation of large-area SERS substrates. Following removal of the copolymer by annealing at 300 °C for 2 h, measurements were obtained under scanning electron microscopy. The results confirmed that 2D GO nanosheets were capable of stabilizing AuNPs, with the final size reaching approximately 40 nm. These AuNPs were adsorbed on both sides of the GO nanosheets. Because the GO nanosheets were merely 5 nm-thick, a good three-dimensional hot-junction effect was generated along the z-axis of the AuNPs. Lastly, the prepared material was used for the SERS detection of rhodamine 6G (R6G), a commonly used highly fluorescent dye. An enhancement factor (EF) of up to 3.5 × 106 was achieved, and the limit of detection was approximately 10-10 M. Detection limits of 10-10 M and < 10-10 M were also observed with the detection of Direct Blue 200 and the biological molecule adenine. It is therefore evident that AuNP/copolymer/GO nanohybrids are large-area flexible SERS substrates that hold great potential in environmental monitoring and biological system detection applications.

Hydrogels of Amphiphilic Triblock Copolymers with Independently Tunable pH and Temperature-Controlled Exchange Dynamics

Hydrogels of Amphiphilic Triblock Copolymers with Independently Tunable pH and Temperature-Controlled Exchange Dynamics

Synthesis of Amphiphilic Triblock Copolymers by ATRP and Coalescence Suppression Effect in Suspension Polymerization

Synthesis of Amphiphilic Triblock Copolymers by ATRP and Coalescence Suppression Effect in Suspension Polymerization

Tuning polymer–blood and polymer–cytoplasm membrane interactions by manipulating the architecture of poly(2-oxazoline) triblock copolymers

Bioactive moieties designed to bind to cell membrane receptors benefit from coupling with polymeric carriers that have enhanced affinity to the cell membrane. When bound to the cell surface, such carriers create a “2D solution” of a ligand with a significantly increased concentration near a membrane-bound receptor compared to a freely water-soluble ligand. Bifunctional polymeric carriers based on amphiphilic triblock copolymers were synthesized from 2-pent-4-ynyl oxazoline, 2-nonyl oxazoline and 2-ethyl oxazoline. Their self-assembly and interactions with plasma proteins and HEK 293 cells were studied in detail. The affinity of these triblock copolymers to HEK 293 cell membranes and organ tissues was tunable by the overall hydrophobicity of the polymer molecule, which is determined by the length of the hydrophobic and hydrophilic blocks. The circulation time and biodistribution of three representative triblock copolymers were monitored after intravenous administration to C57BL/6 albino mice. A prolonged circulation time was observed for polymers with longer hydrophobic blocks, despite their molecular weight being below the renal threshold.