Thermosensitive Micelles Research Articles

Thermosensitive Micelles Gel to Deliver Quercetin Locally for Enhanced Antibreast Cancer Efficacy: An In Vitro Evaluation.

Although quercetin is low cytotoxicity to normal human cells, quercetin is effective against the growth of some tumors. Given the poor blood stability in vivo, insolubility, low delivery efficiency, and poor medicinal properties of quercetin, we developed a local drug delivery system comprising quercetin core's polymer micelles and F127 hydrogel stroma. In vitro evaluation revealed that quercetin core's polymer micelles have excellent antitumor activity and could inhibit the multiplication of 4T1 breast cancer cells through the apoptosis pathway. Meanwhile, a rheological study revealed that the quercetin core's micelles gel possessed excellent properties of hydrogel formation and injectability of liquid preparation as a local drug delivery system after the quercetin core's polymer micelles were loaded into the F127 hydrogel stroma. Our study findings indicated that the drug stability and stable release capacity of quercetin were vastly improved with the composite formulation of the micelles gel. This not only realized drug injectability but also drug storage in the semisolid form, which is a more comfortable and slower drug-releasing form that will eventually exert a proper therapeutic effect. In conclusion, quercetin micellar hydrogel system has better antitumor activity and excellent hydrogel properties.

Photothermally responsive theranostic nanocomposites for near-infrared light triggered drug release and enhanced synergism of photothermo-chemotherapy for gastric cancer.

Near-infrared (NIR) photothermal therapy plays a critical role in the cancer treatment and diagnosis as a promising carcinoma treatment modalities nowadays. However, development of clinical application has been greatly limited due to the inefficient drug release and low tumor accumulation. Herein, we designed a NIR-light triggered indocyanine green (ICG)-based PCL core/P(MEO2MA-b-HMAM) shell nanocomposites (PPH@ICG) and evaluated their therapeutic effects in vitro and in vivo. The anticancer drug 5-fluorouracil (5Fu) and the photothermal agent ICG were loaded into a thermo-sensitive micelle (PPH@5Fu@ICG) by self-assembly. The nanoparticles formed were characterized using transmission electron microscopy, dynamic light scattering, and fluorescence spectra. The thermo-sensitive copolymer (PPH@5Fu@ICG) showed a great temperature-controlled drug release response with lower critical solution temperature. In vitro cellular uptake and TEM imaging proved that PPH@5Fu@ICG nanoparticles can home into the lysosomal compartments under NIR. Moreover, in gastric tumor-bearing nude mice, PPH@5Fu@ICG + NIR group exhibited excellent improvement in antitumor efficacy based on the NIR-triggered thermo-chemotherapy synergy, both in vitro and in vivo. In summary, the proposed strategy of synergistic photo-hyperthermia chemotherapy effectively reduced the 5Fu dose, toxic or side effect, which could serve as a secure and efficient approach for cancer theranostics.

Thermosensitive core-rigid micelles of monomethoxy poly(ethylene glycol)-deoxy cholic acid

BackgroundThermosensitive micelles with rigid cores that exhibit a reversible lower critical solution temperature at 30–35 °C can be applied for drug delivery.MethodHydrophilic monomethoxy poly(ethylene glycol) was conjugated to hydrophobic deoxycholic acid to prepare monomethoxy poly(ethylene glycol)-deoxycholic acid (mPEG-DC). Micelle formation and thermosensitive solution behavior were studied using various methods, including hydrophobic dye solubilization, transmission electron microscopy, dynamic light scattering, turbidity measurement, microcalorimetry, and 1H-NMR spectroscopy. Drug release from the thermosensitive micelles was demonstrated using estradiol, a model drug.ResultsThe mPEG-DC formed micelles with a critical micelle concentration of 0.05 wt.% and an average size of 15 nm. Aqueous mPEG-DC solutions exhibit a lower critical solution temperature (LCST) that is independent of concentration and reversible over heating and cooling cycles. The LCST transition is an entropically driven process involving dehydration of the PEG shell. The thermosensitive mPEG-DC micelles with rigid DC cores were applied as an estradiol delivery system in which estradiol was released, without initial burst, over the 16 days in a diffusion-controlled manner.ConclusionsThis study suggests that mPEG-DCs form thermosensitive micelles with rigid cores that can function as an excellent diffusion-controlled hydrophobic drug delivery system without initial burst release.Graphical Thermosensitive core-rigid micelles of monomethoxy poly(ethylene glycol)-deoxy cholic acid

Hybridization of Poly(oxazoline) and Poly(ethylene oxide)-Based Amphiphilic Copolymers into Thermosensitive Mixed Micelles of Tunable Cloud Point.

This paper reports the development in aqueous solution of mixed micelles of tunable cloud point temperature through blending in various proportions of two copolymers of different chemical natures. For that purpose, a lipid-b-poly(2-isopropyl-2-oxazoline) (lipid-b-P(iPrOx)) copolymer, self-assembling into thermosensitive micelles that phase-separate above a cloud point temperature of 38 °C, was blended in various proportions with commercial C18-b-PEOx. The latter was constituted of a hydrophobic saturated C18 chain and a hydrophilic poly(ethylene oxide) (PEO) block with varying polymerization degrees (x) and does not have any thermosensitive properties on the studied temperature range for any value of x. The different blends were thoroughly characterized by light scattering and UV-visible spectroscopy, revealing that hybridization between both copolymers always occurred, independent of the PEO block length. The resulting mixed micelles present TCP values progressively increasing with the C18-b-PEOx proportion, from 38 to 61 °C. This study demonstrates the relevance of the blending approach to tune the phase separation of micellar systems by formulation rather than by more tedious synthetic efforts. Shifting TCP through this approach extends the range of temperature where lipid-b-P(iPrOx) can find an application.

Synthesis of micelles based on chitosan functionalized with gold nanorods as a light sensitive drug delivery vehicle

This study aims to design photo-triggered micelles by using a natural base polymer. Chitosan was functionalized with thiourea, and in the next step, it was modified by grafting poly(l-lactide), poly(N-isopropylacrylamide), and poly(acrylamide) in determined ratio to form thermo-sensitive micelles. The sulfur content of chitosan@thiourea was measured about 2%. Grafting of polymers on chitosan was characterized by FT-IR and NMR techniques. The critical micellar concentration was measured by using photo luminescence spectroscopy. The size and surface morphology experiments revealed that average size of micelles is about 14 nm, and the length and width of GNRs are about 65 and 19 nm, respectively. The percent of conjugated GNRs to the micelles was about 11%. The conjugation of gold nanorods onto micelles, through gold-thiolate complex formation, induces photo sensitivity to the nano-vehicle. The exposure of NIR light creates local heat by GNRs, shrinkage of thermal-sensitive moiety of micelles, and drug release, simultaneously. Drug release studies demonstrated that at a determined time, paclitaxel was released 38% after exposure to NIR light compared to 15 and 35% in 37 and 45 °C, respectively. The cytotoxicity tests of Paclitaxel loaded micelles were carried out by MTT assay against MCF7 cells.

Thermo-sensitive micelles based on amphiphilic poly(butylene 2-methylsuccinate)-poly(ethylene glycol) multi-block copolyesters as the pesticide carriers

A novel bio-based and biodegradable aliphatic multi-block copolyester, poly(butylene 2-methylsuccinate)-poly(ethylene glycol) (PBMS-PEG), was synthesized from 1,4-butanediol (BDO), 2-methylsuccinate acid (MSA) and poly(ethylene glycol) (PEG) via direct esterification and polycondensation process with tetrabutyl titanate as catalyst. Thermo-sensitive PBMS-PEG micelles were obtained by self-assembly of amphiphilic block copolyesters in aqueous medium by dialysis method. These micelles with different PEG contents have sizes varying from 74.3 nm to 138.3 nm and are stable in water over 200 days without any precipitation. A hydrophobic pesticide, Avermectin, was encapsulated in micelles by the same dialysis method. Such PBMS-PEG micelles can be used as thermo-responsive drug carrier owing to their controlled lower critical solution temperature (LCST) which can be accurately adjusted by varying the PEG proportion. The LCST increases from 27.0 °C to 40.0 °C while increasing the PEG proportion from 30% to 60%. By using the HPLC measurements, the results show when the drug loading is up to 20%, the loading efficiency is still nearly 100%. The properties of these amphiphilic micelles show that the delivery system has a promising potential to be further explored for developing a highly effective and biodegradable hydrophobic-pesticide-release formulation.

Thermosensitive Micelles Encapsulating Phenylalanine Ammonia Lyase Act as a Sustained and Efficacious Therapy Against Colorectal Cancer.

Colorectal cancer has become the third most commonly diagnosed cancer worldwide, which has posed challenges to current conventional therapies. Hence, we propose an alternative approach to the existing therapeutics for colorectal cancer treatment. In this work, we prepared thermosensitive micelles based on poly(ethylene glycol)-poly(caprolactone)poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers (PAL-micelles) that were used to encapsulate phenylalanine ammonia lyase (PAL) as an in situ sustained drug delivery system. In vitro experiments suggested that PAL could inhibit the proliferation and induce apoptosis of tumor cells because the depletion of local phenylalanine blocked the synthesis of corresponding proteins. In addition, the release behavior In vitro and in vivo showed that PAL could be released from PAL-micelles in a controlled manner. Moreover, a significant inhibition of tumor growth was observed in the PAL-micellestreated xenograft mouse model compared to the control groups in vivo, but the systemic toxicity was not noteworthy. The antitumor efficacy was further confirmed by histological analysis of the tumor tissues with hematoxylin and eosin (H&E) and Ki-67 staining. The above results demonstrated that the PAL-micelles system could be considered an alternative strategy for colorectal cancer treatment.

Novel application of NIR photoacoustic absorbing dyes in thermosensitive micelles

Near-infrared (NIR) absorbing dyes have been attached much importance recently, since the promising prospect in photoacoustic (PA) imaging and photothermal (PT) therapy in cancer treatment. In this work, PA signal and PT effect of pyrene derivatives (C12 and C13) prepared via click reaction were evaluated, systematically. It was studied about the further application of loading the representative trisubstituted pyrene derivative (C13) into biocompatible liposomes and subsequent PA measurement. C13 showed the excellent PA effect, whether it's embedded or not. Since temperature increment of the dyes were remarkable in PT test, the same representative derivative C13 was picked and loaded into PNIPAM-b-PNBM polymer micelles as photothermal conversion agent. Preliminary studies suggested that the trisubstituted pyrene derivatives had great potential to replace the function of temperature stimulus.

Magnetic thermosensitive micelles with upper critical solution temperature for NIR triggered drug release.

Smart micelles which undergo dramatic property changes in response to temperature have aroused extensive interest in specific cancer therapy. To date, studies on thermosensitive polymers have mainly focused on lower critical solution temperature (LCST) polymers. Materials with upper critical solution temperature (UCST) which can swell and disassemble at elevated temperatures have much less been documented, although they have been reported to be ideal carriers for quick and complete drug release upon applying a stimulus. Here, magnetic micelles with UCST are developed for doxorubicin (DOX) delivery. Hydrophobic Fe3O4 magnetic nanoparticles with a particle size of 8 nm are fabricated and enveloped in an amphiphilic polymer, poly(AAm-co-AN)-g-PEG (PAAP), to form UCST micelles (Fe3O4@PAAP). The resulting micelles exhibit excellent photothermal effects and burst drug release in response to near infrared (NIR) laser irradiation. The in vitro and in vivo antitumor experiments indicate that DOX-Fe3O4@PAAP micelles can significantly enhance the therapeutic effect upon NIR light irradiation. A novel thermosensitive platform is thus offered for in situ drug release and combined photothermal-chemotherapy, holding a favorable prospect for cancer therapy.

The application of small organic π-conjugated discotic derivatives in photoacoustic imaging and photothermal conversion

Near-infrared absorbing dyes are catching people’s attention as they are committed to find materials with greater photoacoustic (PA) and photothermal (PT) effect. In this study, a new series of organic π-conjugated discotic derivatives synthesized via [2 + 2] click chemistry were introduced. The PA intensity and PT conversion effect of the derivatives were monitored. It was found that the π-conjugated discotic derivatives had a proper absorption peak and PA intensity by introducing the click regents. Furthermore, the PA intensity remained relatively high, while B12 molecules were embedded in hydrophobic phospholipid bilayer of liposomes (B12⊂L). The application in biological therapy for tumors become possible as the toxicity of B12⊂L was low. What’s more, when B12 molecules embedded in poly (N-isopropylacrylamide)-block-poly (2-nitrobenzyl methacrylate) (PNIPAM-b-PNBM) thermosensitive micelles were irradiated by laser, the molecules could take the place of direct temperature stimulus. This work affords us a way to solve the problem in which direct temperature stimulus is inapplicable.

NIR absorbing thiophene derivatives with photoacoustic and photothermal effect used in drug release

Small near-infrared (NIR) absorbing organic molecules are highly demanded for photoacoustic (PA) imaging and photothermal (PT) therapy recently. In this study, the PA imaging and PT effect of a novel series of small organic π-conjugated NIR absorbing thiophene derivatives, synthetized via click reaction, were characterized carefully. It was interesting to note that derivatives clicked by F4-TCNQ showed a red shift of PA peaks, compared to those clicked by TCNQ. Besides, it turned out that the PA intensity and PT conversion efficiency of the series of NIR absorbing dyes were extremely high at a low concentration. Surprisingly, the PA values remained high when H43 molecules were loaded in liposomes in cells. To solve the problem that the liposomes behaved incapable of releasing drugs, H43, the representative one of the thiophene derivatives, was innovatively loaded together with Nile Red in temperature-responsive micelles, where H43 acted as a great photothermal conversion agent, induced the micelles to shrink when the NIR light irradiated and the maximum temperature of the solution was 32 °C. The cumulative release of H43 micelles was considerable in comparison to that immersed in 32 °C water bath. The systematical study of the organic NIR dyes provides a new strategy to design NIR absorbing dyes with high PA intensity and puts forward a fresh idea that NIR light stimulus could replace temperature stimulus of thermosensitive micelles by using NIR dyes to realize the combination of PA imaging, PT therapy and NIR-responsive drug release therapy.

Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle.

The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide) and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN) with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT), high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly. The shikonin is then entrapped in a degradable inner core resulting in a shikonin-loaded thermosensitive nanomicelle (STN) with a VPTT of ~40°C. Compared with small-molecular shikonin, the in vitro cellular internalization and cytotoxicity of STN against breast cancer cells (Michigan Cancer Foundation-7) are obviously enhanced. In addition, the therapeutic effect is further enhanced by the programmed cell death (PCD) specifically evoked by shikonin. Interestingly, both the proliferation inhibition and PCD are synergistically promoted as T > VPTT, namely the temperature-regulated passive targeting. Consequently, as intravenous injection is administered to the BALB/c nude mice bearing breast cancer, the intratumor accumulation of STNs is significantly increased as T > VPTT, which is regulated by the in-house developed heating device. The in vivo antitumor assays against breast cancer further confirm the synergistically enhanced therapeutic efficiency. The findings of this study indicate that STN is a potential effective nanoformulation in clinical cancer therapy.

Tuning the Thermo-Sensitivity of Micellar Systems through a Blending Approach

This paper reports an original and easy route toward thermosensitive micelles based on a lipidic core and with adjustable cloud point temperatures (TCP) through a simple blending approach between two copolymers of different TCP. The cationic ring-opening polymerization (CROP) of various 2-alkyl-2-oxazoline monomers was first investigated from both mesylated and tosylated lipoinitiators and different lipid-b-poly(2-methyl-2-oxazoline), lipid-b-poly(2-ethyl-2-oxazoline), lipid-b-poly(2-isopropyl-2-oxazoline) and lipid-b-poly((2-ethyl-2-oxazoline)-co-(2-isopropyl-2-oxazoline)) copolymers were synthesized. Blending of lipid-b-p(EtOx) and lipid-b-p(iPrOx) copolymers in various proportions were then prepared and their TCP investigated through UV–visible spectroscopy. Very interesting results were obtained as the blends exhibit a single TCP ranging from 35 to 45 °C. Furthermore, the blends TCP correspond to those of the statistical lipid-b-p((EtOx)-co-(iPrOx)) for the same p(EtOx)/p(iPrOx) content up to 52 wt % ...

Preparation and characterization of magnetic thermosensitive fluorouracil micelles

In this study, we synthesized P(NIPAM-co-DMAM)-b-PLA polymers with free radical polymerization and ring-opening addition polymerization, and immediately assembled ‘dextran magnetic layered double hydroxide fluorouracil’ (DMF) magnetic particles into the core of the amphiphilic polymer micelles with synchronous hydration and dialysis, to generate a magnetic thermosensitive fluorouracil drug delivery system. The basic properties of the micelle particles, such as the core–shell-type structure, size, and zeta potential, were studied with 1H-NMR, FTIR, TEM, TGA, laser nanoparticle size analysis, and other characterization techniques. The thermosensitivity of the micelles was investigated by measuring parameters such as the lower critical solution temperature (LCST) and the relationship between the particle size variation and temperature. The drug release curves for the micelles at different temperatures were constructed with a dialysis method. The LCST of the triblock polymers was 42 °C. The particle sizes of the blank micelles and DMF-loaded micelles were 493.6 ± 1.8 nm and 464.9 ± 4.1 nm, respectively, at 25 °C. When the temperature was higher than LSCT, a contraction phase change in the micelle structure occurred, a significant characteristic of the core–shell-type structure, and reversible phase transition phenomena. The release behavior of the drug-loaded micelles showed obvious variations with temperature. Therefore, the magnetic thermosensitive fluorouracil drug delivery system has a good magnetic response and excellent temperature controlled release characteristics, so it can be used as a drug delivery system in magnetically and thermally targeted chemotherapy for tumors.

Passive targeting of thermosensitive diblock copolymer micelles to the lungs: synthesis and characterization of poly(N-isopropylacrylamide)-block-poly(ε-caprolactone).

BackgroundAmphiphilic poly(N-isopropylacrylamide)-block-poly(ε-caprolactone) (PNiPAAm-b-PCL) copolymers were synthesized by ring-opening polymerization to form thermosensitive micelles as nanocarriers for bioimaging and carboplatin delivery.ResultsThe critical micelle concentration increased from 1.8 to 3.5 mg/l following the decrease of the PNiPAAm chain length. The copolymers revealed a lower critical solution temperature (LCST) between 33 and 40°C. The copolymers self-assembled to form spherical particles of 146–199 nm in diameter. Carboplatin in micelles exhibited a slower release at 37°C relative to that at 25°C due to the gel layer formation on the micellar shell above the LCST. The micelles containing dye or carboplatin were intravenously injected into the rats for in vivo bioimaging and drug biodistribution. The bioimaging profiles showed a significant accumulation of micelles in the lungs. The micelles could minimize the reticuloendothelial system (RES) recognition of the dye. In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 μg/mg by the micelles as compared to the control solution. Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles.ConclusionThis study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-015-0103-7) contains supplementary material, which is available to authorized users.

Thermosensitive tribrachia star-shaped s-P(NIPAM-co-DMAM) random copolymer micelle aggregates: Preparation, characterization, and drug release applications.

Tribrachia star-shaped random copolymers with tunable thermosensitive phase transition temperature were designed and synthesized via a simple one-pot ammonolysis reaction approach with trimesic acid as cores. The self-assembly micellization behavior of the copolymers in aqueous solution was examined by surface tension, UV-vis transmittance, transmission electron microscope, and dynamic light scattering measurements, etc. The results indicated that the resultant copolymers formed thermosensitive micelle aggregates through hydrophobic interactions among the isopropyl groups of poly(N-isopropylacrylamide) PNIPAM chains and inter-star association at a polymer concentration above critical aggregation concentrations from 4.06 to 6.55 mg L(-1), with a cloud point range from 36.6℃ to 52.1℃, and homogeneously distributed micelle size below 200 nm. The arm length and the compositional ratios of the two comonomers had effect on physicochemical properties of the polymer micelle aggregates. Particularly, the cloud point values were enhanced as the (N,N-dimethylacrylamide) DMAM monomer was introduced and reached to 36.6℃ and 41.0℃-44.7℃ when the mass ratio of NIPAM to DMAM was 90:10 and 80:20, respectively. The thermo-triggered drug release and cytotoxicity were evaluated to confirm the applicability of the random copolymer micelle aggregates as novel drug targeted release carriers.

Body temperature sensitive micelles for MRI enhancement.

A novel thermo-sensitive micelle contrast agent and its enhancement of MRI contrast with temperature are reported. The morphology changes sharply near 37 °C, resulting in a significant amplification of the CEST signal. This enables detection of small changes in body temperature.

Synthesis, characterization, conformation and self-assembly behavior of polypeptide-based brush with oligo (ethylene glycol) side chains

A new polypeptide-based copolymer brush composed of poly (γ-propargyl-L-glutamate)-block-poly (propylene oxide)-block-poly (γ-propargyl-L-glutamate) backbone (PPLG-b-PPO-b-PPLG) and oligo (ethylene glycol) (PEG) side-chain was synthesized by combination of N-carboxyanhydride ring-opening polymerization and click chemistry. Nearly 100% grafting efficiency was achieved by copper-catalyzed azide-alkyne Huisgen 1,3-dipolar cycloaddition (CuAAc) reaction. The α-helical conformation adopted by the grafted polypeptide blocks in water was relatively stable and showed a reversible change in a heating–cooling circle from 5 to 70°C. It displayed weak stability against elevated temperature but still reversible changes in the presence of 0.47M NaCl. The brushes were amphiphilic and could self-assemble into thermo-sensitive micelles in water. Big micelles could break into small micelles upon heating due to the improved solubility.

Prevention of desiccation induced postsurgical adhesion by thermosensitive micelles

Tissue desiccation is a common cause of postsurgical peritoneal adhesion, which leads a variety of adverse consequences in clinic. Until now, many approaches have been advocated to prevent postsurgical adhesions, but the therapeutic effects were not very encouraging. In this work, biodegradable and thermosensitive poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) (PCL–PEG–PCL) micelles were prepared and assigned for anti-adhesion studies. The micelles were a free flowing sol at low temperature, but instantly inverted into a non-flowing gel at physiological temperature, which could serve as a potential candidate as anti-adhesion barrier. A novel cecum desiccation rat model was established and used for anti-adhesion studies. The micelles were sol state before use, which could cover the injured cecum unrestrictedly, and then formed gel in body temperature and adhered to the injured sites. All the rats in the control group developed adhesions with score 5 or 4, whereas none in the micelle-treated group developed adhesions with score 5 or 4 (P<0.001, Mann–Whitney U test). Histopathological assessment also confirmed that the micelles exhibited excellent anti-adhesion effects on desiccation-induced peritoneal adhesion. Adhesiveness and degradation behavior of the micelles suggested that the micelles could adhere to the injured cecum and prevent adhesion in the critical time of healing process. The results indicated that the thermosensitive micelles could serve as an effective anti-adhesion barrier.

Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion

Ischemia-induced adhesion is very common after surgery, and leads to severe abdominal adhesions. Unfortunately, many existing barrier agents used for adhesion prevention have only limited success. The objective of this study is to evaluate the efficacy of biodegradable and thermosensitive poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) micelles for the prevention of postoperative ischemia-induced adhesion. We found that the synthesized PCL–PEG–PCL copolymer could self-assemble in an aqueous solution to form micelles with a mean size of 40.1±2.7 nm at 10°C, and the self-assembled micelles could instantly turn into a nonflowing gel at body temperature. In vitro cytotoxicity tests suggested that the copolymer showed little toxicity on NIH-3T3 cells even at amounts up to 1,000 μg/mL. In the in vivo test, the postsurgical ischemic-induced peritoneal adhesion model was established and then treated with the biodegradable and thermosensitive micelles. In the control group (n=12), all animals developed adhesions (mean score, 3.58±0.51), whereas three rats in the micelles-treated group (n=12) did not develop any adhesions (mean score, 0.67±0.78; P<0.001, Mann–Whitney U-test). Both hematoxylin and eosin and Masson trichrome staining of the ischemic tissues indicated that the micelles demonstrated excellent therapeutic effects on ischemia-induced adhesion. On Day 7 after micelle treatment, a layer of neo-mesothelial cells emerged on the injured tissues, which confirmed the antiadhesion effect of the micelles. The thermosensitive micelles had no significant side effects in the in vivo experiments. These results suggested that biodegradable and thermosensitive PCL–PEG–PCL micelles could serve as a potential barrier agent to reduce the severity of and even prevent the formation of ischemia-induced adhesions.