Biodegradable Block Copolymers Research Articles

Solvent-induced morphological diversification in poly( l-lactide- b-ɛ-caprolactone) block copolymer thin films

Biodegradable block copolymer of poly( l-lactide- b-ɛ-caprolactone) (P(LA- b-CL)) was dissolved in various solvents with different solubility as well as volatility, and spin-cast on a highly oriented pyrolytic graphite (HOPG) to prepare thin films. The surface morphologies were observed by using atomic force microscopy (AFM) in a dynamic force (tapping) mode. Particle like morphology was found in the thin films prepared form the dichloromethane and acetone. Higher volatility of dichloromethane and acetone resulted in the reflection of the particle like objects in the solution to HOPG substrate. In contrast, the P(LA- b-CL)s in toluene and 1,4-dioxane exhibited different morphologies compared to those in dichloromethane and acetone. Lower volatility of toluene and 1,4-dioxane assisted the epitaxial crystallization of PCL component along the HOPG lattice, that was revealed by enzymatic degradation of PLLA component by proteinase K. Thus, adjusting the solubility and solvent volatility for the film formation provided morphological divergence of the P(LA- b-CL) block copolymer, and this technique would be applicable for the surface patterning of biodegradable polymers.

A Bioinspired Route to Various Siliceous Vesicular Structures

Various siliceous nanostructures have been successfully synthesized through the co-organization of organic molecules and inorganic silica source under mild pH conditions (pH approximately 5). A biodegradable block copolymer P123 [EO20PO70EO20, EO is poly (ethylene oxide), PO is poly (propylene oxide)] is employed as a marcomolecular template and Na2SiO39H2O as a silica source. By changing the concentrations of the reactants and/or reaction temperature, siliceous multilamellar vesicles, unilamellar nano-foams and multilamellar vesicles with sponge-like walls have been obtained. Our work provides a convenient and bioinspired route to obtain siliceous nanostructured materials with adjustable and multi-level pore structures as well as rich morphologies, which is important to understand the biomineralization mechanism. Such artificial silica nanoporous materials may find potential applications in catalysis, separations, electronics, and photonics, etc.

Novel Degradable Co-polymers of Polypyrrole Support Cell Proliferation and Enhance Neurite Out-Growth with Electrical Stimulation

Synthetic polymers such as polypyrrole (PPy) are gaining significance in neural studies because of their conductive properties. We evaluated two novel biodegradable block co-polymers of PPy with poly(ε-caprolactone) (PCL) and poly(ethyl cyanoacrylate) (PECA) for nerve regeneration applications. PPy–PCL and PPy–PECA co-polymers can be processed from solvent-based colloidal dispersions and have essentially the same or greater conductivity (32 S/cm for PPy–PCL, 19 S/cm for PPy–PECA) compared to the PPy homo-polymer (22 S/cm). The PPy portions of the co-polymers permit electrical stimulation whereas the PCL or PECA blocks enable degradation by hydrolysis. For in vitro tests, films were prepared on polycarbonate sheets by air brushing layers of dispersions and pressing the films. We characterized the films for hydrolytic degradation, electrical conductivity, cell proliferation and neurite extension. The co-polymers were sufficient to carry out electrical stimulation of cells without the requirement of a metallic conductor underneath the co-polymer film. In vitro electrical stimulation of PPy–PCL significantly increased the number of PC12 cells bearing neurites compared to unstimulated PPy–PCL. For in vivo experiments, the PPy co-polymers were coated onto the inner walls of nerve guidance channels (NGCs) made of the commercially available non-conducting biodegradable polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV). The NGCs were implanted in a 10 mm defect made in the sciatic nerve of rats, and harvested after 8 weeks. Histological staining showed axonal growth. The studies indicated that these new conducting degradable biomaterials have good biocompatibility and support proliferation and growth of PC12 cells in vitro (with and without electrical stimulation) and neurons in vivo (without electrical stimulation).

Synthesis of biocompatible and biodegradable block copolymers of polyvinyl alcohol‐block‐poly(ε‐caprolactone) using metal‐free living cationic polymerization

AbstractApplications of metal‐free living cationic polymerization of vinyl ethers using HCl·Et2O are reported. Product of poly(vinyl ether)s possessing functional end groups such as hydroxyethyl groups with predicted molecular weights was used as a macroinitiator in activated monomer cationic polymerization of ε‐caprolactone (CL) with HCl·Et2O as a ring‐opening polymerization. This combination method is a metal‐free polymerization using HCl·Et2O. The formation of poly(isobutyl vinyl ether)‐b‐poly(ε‐caprolactone) (PIBVE‐b‐PCL) and poly(tert‐butyl vinyl ether)‐b‐poly(ε‐caprolactone) (PTBVE‐b‐PCL) from two vinyl ethers and CL was successful. Therefore, we synthesized novel amphiphilic, biocompatible, and biodegradable block copolymers comprised polyvinyl alcohol and PCL, namely PVA‐b‐PCL by transformation of acid hydrolysis of tert‐butoxy moiety of PTBVE in PTBVE‐b‐PCL. The synthesized copolymers showed well‐defined structure and narrow molecular weight distribution. The structure of resulting block copolymers was confirmed by 1H NMR, size exclusion chromatography, and differential scanning calorimetry. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5169–5179, 2009

Tunable Thermosensitivity of Biodegradable Polymer Micelles of Poly(ε-caprolactone) and Polyphosphoester Block Copolymers

The development of thermoresponsive and biodegradable polymer nanoparticles with tunable thermosensitivity and biocompatibility is of great interest, especially for in vivo biomedical applications. In this study, biodegradable polymer micellar nanoparticles with tunable thermosensitivity are reported. They are based on various biodegradable block copolymers of hydrophobic poly(e-caprolactone) and thermosensitive polyphosphoesters, obtained through poly(e-caprolactone)/stannous octoate coinitiated random ring-opening polymerization of cyclic phosphoester monomers. The thermosensitive micellar shells of nanoparticles turn out to be more hydrophobic and result in aggregates in aqueous solution when the temperature is higher than their lower critical solution temperature (LCST). The phase transition temperatures can be adjusted by controlling the molecular weights and the compositions of biodegradable polyphosphoester blocks. Decreased molecular weights of poly(ethyl ethylene phosphate) (PEEP) lead to higher ...

Synthesis and characterization of biodegradable block copolymer pluronic‐b‐poly(L‐lysine)

AbstractThis study presented the investigations on the synthesis of a novel biodegradable block copolymer of pluronic‐b‐poly(L‐lysine) (pluronic‐b‐PLL), which combined the characteristics of aliphatic polyester and poly(amino acids). The synthesis work started with end‐capping of pluronic with N‐t‐butoxycarbonyl‐L‐phenylalanine using dicyclohexylcarbodiimide in the presence of 4‐dimethylaminopyridine, followed by a deprotection process to obtain the amino‐terminated pluronic; the new primary amino group in the modified pluronic initiated ring‐opening polymerization of amino acid N‐carboxyanhydride, which afforded the pluronic‐b‐poly(Nε‐(Z)‐L‐lysine) block copolymer. Finally, removal of the side‐chain Nε‐(carbonybenzoxy) end protecting groups yields the block copolymer of pluronic‐b‐PLL. The products were characterized by 1H‐NMR, FTIR, DSC, and GPC. The block copolymer micelle containing the anticancer drug paclitaxel was prepared by the double emulsion method. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Superparamagnetic Iron Oxide Nanoparticles Encapsulated in Biodegradable Thermosensitive Polymeric Micelles: Toward a Targeted Nanomedicine Suitable for Image-Guided Drug Delivery

Superparamagnetic iron oxide nanoparticles (SPIONs) have been receiving great attention lately due to their various biomedical applications, such as in MR imaging and image guided drug delivery. However, their systemic administration still remains a challenge. In this study, the ability of biodegradable thermosensitive polymeric micelles to stably encapsulate hydrophobic oleic-acid-coated SPIONs (diameter 5-10 nm) was investigated, to result in a system fulfilling the requirements for systemic administration. The micelles were composed of amphiphilic, thermosensitive, and biodegradable block copolymers of poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide dilactate] (mPEG-b-p(HPMAm-Lac2)). The encapsulation was performed by addition of one volume of SPIONs in THF to nine volumes of a cold aqueous mPEG-b-p(HPMAm-Lac2) solution (0 degrees C; below the cloud point of the polymer), followed by rapid heating of the resulting mixture to 50 degrees C, to induce micelle formation ("rapid heating" procedure). Dynamic light scattering (DLS) measurements revealed that approximately 200 nm particles (PDI=0.2) were formed, while transmission electron microscopy (TEM) analysis demonstrated that clusters of SPIONs were present in the core of the micelles. A maximum loading of 40% was obtained, while magnetic resonance imaging (MRI) scanning of the samples demonstrated that the SPION-loaded micelles had high r2 and r2* relaxivities. Furthermore, the r2* values were found to be at least 2-fold higher than the r2 values, confirming the clustering of the SPIONs in the micellar core. The particles showed excellent stability under physiological conditions for 7 days, even in the presence of fetal bovine serum. This, together with their ease of preparation and their size of approximately 200 nm, makes these systems highly suitable for image-guided drug delivery.

Thermoresponsive Block Copolymers of Poly(ethylene glycol) and Polyphosphoester: Thermo-Induced Self-Assembly, Biocompatibility, and Hydrolytic Degradation

Novel thermoresponsive block copolymers of poly(ethylene glycol) and polyphosphoester were synthesized, and the thermo-induced self-assembly, biocompatibility, and hydrolytic degradation behavior were studied. The block copolymers with various molecular weights and compositions were synthesized through ring-opening polymerization of 2-ethoxy-2-oxo-1,3,2-dioxaphospholane (EEP) and 2-isopropoxy-2-oxo-1,3,2-dioxaphospholane (PEP) using poly(ethylene glycol) monomethyl ether (mPEG) as the initiator and stannous octoate as the catalyst. The obtained block polymers exhibited thermo-induced self-assembly behavior, demonstrated by dynamic light scattering and UV-vis measurements using 1,6-diphenyl-1,3,5-hexatriene as the probe. It was found that the critical aggregation temperature (CAT) of the block copolymers shifted to higher temperature with increased molecular weight of mPEG, while copolymerization with more hydrophobic monomer PEP led to lower transition temperature; thus, the CAT can be conveniently adjusted. The block copolymers did not induce significant hemolysis and plasma protein precipitation. In vitro MTT and live/dead staining assays indicated they are biocompatible, and the biocompatibility was further demonstrated in vivo by the absence of local acute inflammatory response in mouse muscle following intramuscular injection. Unlike most frequently studied thermoresponsive poly(N-isopropylacrylamide), polyphosphoesters were hydrolytically degradable in aqueous solution that was proven by gel permeation chromatography and NMR analyses, and the degradation products were proven to be nontoxic to HEK293 cells. Therefore, with good biocompatibility and thermoresponsiveness, these biodegradable block copolymers of mPEG and polyphosphoesters are promising as stimuli-responsive materials for biomedical applications.

Biodegradable polymersomes for controlled drug release

Hydrophilic fluorescein isothiocyanate-dextran (FD, mol. weight 4000 g/mol) could be readily incorporated in polymersomes (PS) made of different amphiphilic biodegradable block copolymers based on PEG-PDLLA, PEG-PCL, and PEG-PTMC. The FD release from these polymersomes in PBS at 37 °C was complete within approximately 10 days. Both the length of the hydrophobic block as well as the type of the hydrophobic block have a major influence on the release rate of FD from the PS, while the hydrophilic block length has only a minor influence on the release rate. For all systems the release of FD follows first order kinetics, confirming that the FD containing polymersome system is a membrane controlled reservoir system.

Synthesis, characterization and biocompatibility of novel biodegradable poly[((R)‐3‐hydroxybutyrate)‐block‐(D,L‐lactide)‐block‐(ε‐caprolactone)] triblock copolymers

AbstractBACKGROUND: Biodegradable block copolymers have attracted particular attention in both fundamental and applied research because of their unique chain architecture, biodegradability and biocompatibility. Hence, biodegradable poly[((R)‐3‐hydroxybutyrate)‐block‐(D,L‐lactide)‐block‐(ε‐caprolactone)] (PHB‐PLA‐PCL) triblock copolymers were synthesized, characterized and evaluated for their biocompatibility.RESULTS: The results from nuclear magnetic resonance spectroscopy, gel permeation chromatography and thermogravimetric analysis showed that the novel triblock copolymers were successfully synthesized. Differential scanning calorimetry and wide‐angle X‐ray diffraction showed that the crystallinity of PHB in the copolymers decreased compared with methyl‐PHB (LMPHB) oligomer precursor. Blood compatibility experiments showed that the blood coagulation time became longer accompanied by a reduced number of platelets adhering to films of the copolymers with decreasing PHB content in the triblocks. Murine osteoblast MC3T3‐E1 cells cultured on the triblock copolymer films spread and proliferated significantly better compared with their growth on homopolymers of PHB, PLA and PCL, respectively.CONCLUSION: For the first time, PHB‐PLA‐PCL triblock copolymers were synthesized using low molecular weight LMPHB oligomer as the macroinitiator through ring‐opening polymerization with D,L‐lactide and ε‐caprolactone. The triblock copolymers exhibited flexible properties with good biocompatibility; they could be developed into promising biomedical materials for in vivo applications. Copyright © 2008 Society of Chemical Industry

Synthesis of biodegradable block copolymer acyl-imine with catalyst of zinc powder

This paper reported about a polymer of acyl imine synthesized by 3-morpholinone(M) and e-caprolactone(CL) with zinc powder as catalyst. The influence of reaction temperature, reaction time and monomer ratio on the copolymerization reaction was studied. Investigation of monomer reaction ratio and differential scanning calorimeter (DSC) indicated that the copolymer poly(3-morpholinone-e-caprolactone) was a block copolymer, solubility in water, degradation characteristics in vitro and controlled release of 5-FU was also studied. The results showed the hydrophilicity of the copolymer increased with the increasing of M content in the copolymer. With the enhancement of hydrophilicity its degradation rate and drug releasing rate increased as well.

Progress in the study of pH and temperature sensitive biodegradable block copolymers

pH and temperature sensitive biodegradable block copolymers are some macromolecules connected by biodegradable materials and pH sensitive monomers according to a certain sequence, or biodegradable polyesters polymerized themselves. On the basis of pertinent documents, the development of pH and temperature sensitive biodegradable block copolymers was introduced, involving their mechanism of action and potential application. PH and temperature sensitive biodegradable block copolymers could control the drug release rate freely, avoiding burst effect. Besides, the biocompatibility of these biodegradable materials is also excellent. So the use of pH and temperature sensitive biodegradable block copolymers as biodegradable drug delivery devices has attracted considerable interest in the intelligent drug delivery system.

Drug-loaded nano/microbubbles for combining ultrasonography and targeted chemotherapy

A new class of multifunctional nanoparticles that combine properties of polymeric drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated drug delivery has been developed. At room temperature, the developed systems comprise perfluorocarbon nanodroplets stabilized by the walls made of biodegradable block copolymers. Upon heating to physiological temperatures, the nanodroplets convert into nano/microbubbles. The phase state of the systems and bubble size may be controlled by the copolymer/perfluorocarbon volume ratio. Upon intravenous injections, a long-lasting, strong and selective ultrasound contrast is observed in the tumor volume indicating nanobubble extravasation through the defective tumor microvasculature, suggesting their coalescence into larger, highly echogenic microbubbles in the tumor tissue. Under the action of tumor-directed ultrasound, microbubbles cavitate and collapse resulting in a release of the encapsulated drug and dramatically enhanced intracellular drug uptake by the tumor cells. This effect is tumor-selective; no accumulation of echogenic microbubbles is observed in other organs. Effective chemotherapy of the MDA MB231 breast cancer tumors has been achieved using this technique.

Multifunctional Nanoparticles for Combining Ultrasonic Tumor Imaging and Targeted Chemotherapy

Drug delivery in polymeric micelles combined with tumor irradiation by ultrasound results in effective drug targeting, but this technique requires prior tumor imaging. A technology that combined ultrasound imaging with ultrasound-mediated nanoparticle-based targeted chemotherapy could therefore have important applications in cancer treatment. Mixtures of drug-loaded polymeric micelles and perfluoropentane (PFP) nano/microbubbles stabilized by the same biodegradable block copolymer were prepared. Size distribution of nanoparticles was measured by dynamic light scattering. Cavitation activity (oscillation, growth, and collapse of microbubbles) under ultrasound was assessed based on the changes in micelle/microbubble volume ratios. The effect of the nano/microbubbles on the ultrasound-mediated cellular uptake of doxorubicin (Dox) in MDA MB231 breast tumors in vitro and in vivo (in mice bearing xenograft tumors) was determined by flow cytometry. Statistical tests were two-sided. Phase state and nanoparticle sizes were sensitive to the copolymer/perfluorocarbon volume ratio. At physiologic temperatures, nanodroplets converted into nano/microbubbles. Doxorubicin was localized in the microbubble walls formed by the block copolymer. Upon intravenous injection into mice, Dox-loaded micelles and nanobubbles extravasated selectively into the tumor interstitium, where the nanobubbles coalesced to produce microbubbles with a strong, durable ultrasound contrast. Doxorubicin was strongly retained in the microbubbles but released in response to therapeutic ultrasound. Microbubbles cavitated under the action of tumor-directed ultrasound, which enhanced intracellular Dox uptake by tumor cells in vitro to a statistically significant extent relative to that observed with unsonicated microbubbles (drug uptake ratio = 4.60; 95% confidence interval [CI] = 1.70 to 12.47; P = .017) and unsonicated micelles (drug uptake ratio = 7.97; 95% CI = 3.72 to 17.08; P = .0032) and resulted in tumor regression in the mouse model. Multifunctional nanoparticles that are tumor-targeted drug carriers, long-lasting ultrasound contrast agents, and enhancers of ultrasound-mediated drug delivery have been developed and deserve further exploration as cancer therapeutics.

A thermosensitive hydrogel based on biodegradable amphiphilic poly(ethyleneglycol)–polycaprolactone–poly(ethylene glycol) block copolymers**This work was financially supported by the Chinese Key Basic Research Program(2004CB518800 and 2004CB518807), and the Sichuan Key Project of Science andTechnology (06(05SG022-021-02)).

A series of low molecular weight poly(ethylene glycol)–polycaprolactone–poly(ethyleneglycol) (PEG–PCL–PEG) biodegradable block copolymers were successfully synthesizedusing isophorone diisocyanate (IPDI) as the coupling agent, and were characterized using1H NMR and Fourier transform infrared spectroscopy. The aqueous solutions of the PEG–PCL–PEGcopolymers displayed a special thermosensitive gel–sol transition when the concentration wasabove the corresponding critical gel concentration. Gel–sol phase diagrams were recordedusing the test-tube-inversion method; they depended on the hydrophilic/hydrophobicbalance in the macromolecular structure, as well as some other factors, including theheating history, volume, and the ageing time of the copolymer aqueous solutions anddissolution temperature of the copolymers. As a result, the gel–sol transition temperaturerange could be altered, which might be very useful for application in injectable drugdelivery systems.

Preparation and characterization of fenofibrate-loaded PLA–PEG microspheres

A series of biodegradable block copolymer of poly(lactide)(PLA)/poly(ethylene glycol) (PEG) were prepared by Ring-Opening polymerization of D, L-lactide, using stannous octoate as a catalyst. By nanoprecipitation method, the PLA-PEG can be made into microspheres containing fenofibrate, which is a kind of important cholesterol-lowering drugs. The purpose of this study is to investigate the effect of the copolymer composition on the size, the entrapment and the release behavior of the fenofibrate loaded microspheres. The microspheres can be achieved with small size below 100 nm, better encapsulation efficiencies of more than 55.3% and slower release rates. The release of fenofibrate from microsphere would reach the balance first, when the microsphere prepared by high proportion of hydrophilic PEG block. And the release property of fenofibrate/PLA-PEG microsphere was better than Lipanthyl (a commercial capsule of fenofibrate). It was observed that the composition of PLA-PEG copolymer played a major role in encapsulation efficiency of microspheres and release rates.

Synthesis and characterization of a thermosensitive hydrogel based on biodegradable amphiphilic PCL-Pluronic (L35)-PCL block copolymers

A series of PCL–Pluronic–PCL biodegradable block copolymers were successfully synthesized by ring opening polymerization of ɛ-caprolactone (ɛ-CL) initiated by Pluronic (PEG–PPG–PEG) macromonomer, which were characterized by 1H NMR and FTIR. Their aqueous solution displayed special gel–sol transition with temperature increased from 4 °C to 70 °C, when the concentration was above corresponding critical gel concentration (CGC). The gel–sol phase diagram was recorded using test tube-inverting method, which depended not only on the hydrophilic/hydrophobic balance in macromolecular structure, but also on heating history of copolymer's aqueous solution. As a result, the gel–sol transition temperature range could be altered according to its practical application, which would be very useful as injectable drug delivery system. To illuminate the mechanism of gel–sol transition, we introduced a typical double layers shell/core structure of PCL–Pluronic–PCL micelles here. The hydrophobic interactions and partly crystallization might be the key gelation machanism for such special gel–sol transition behavior of PCL–Pluronic–PCL aqueous solution.

New three-arm amphiphilic and biodegradable block copolymers composed of poly( ε-caprolactone) and poly( N-vinyl-2-pyrrolidone). Synthesis, characterization and self-assembly in aqueous solution

The synthesis, characterization and the self-assembly process of a novel biodegradable block copolymer containing a poly( ε-caprolactone), PCL, central block and three poly( N-vinyl-2-pyrrolidone), PVP, arms are reported. Three samples with different amounts of PVP were investigated. The copolymers were characterized by FTIR spectroscopy, 1H NMR and viscosity measurements. The composition and the molecular weights of the block copolymers were established using size exclusion chromatography SEC and 1H NMR. Micelle formation by these copolymers was monitored by using the vibrational fine structure of pyrene monomer fluorescence and the critical aggregation concentrations, cac, of the copolymers in aqueous solution were determined using sigmoid Boltzmann-type fitting of the fluorescence data. Dynamic light scattering measurements showed a bimodal size distribution for the copolymers in solution, indicating that the micellization is an intermolecular process. Partitioning coefficients of pyrene between copolymer micelles and water were also determined and increase in magnitude with increasing ε-caprolactone content of the copolymer.

PH/temperature sensitive poly(ethylene glycol)-based biodegradable polyester block copolymer hydrogels

Novel pH and temperature sensitive biodegradable block copolymers composed of poly(ethylene glycol) (PEG), polyglycolide (GA), ɛ-caprolactone (CL) and sulfamethazine oligomers (OSMs) were synthesized by ring opening polymerization and 1,3-dicyclohexyl-carbodiimide (DCC) mediated coupling reactions. Their physicochemical properties in aqueous media were characterized by 1H NMR spectroscopy and gel permeation spectroscopy. The sol–gel phase transition behavior of OSM–PCGA–PEG–PCGA–OSM block copolymers was investigated both in solution and injection to PBS buffer at pH 7.4 and 37 °C. Aqueous solutions of OSM–PCGA–PEG–PCGA–OSM changed from a sol to a gel phase with increasing temperature and decreasing pH. The sol–gel transition properties of these block copolymers are influenced by the hydrophobic/hydrophilic balance of the copolymers, block length, hydrophobicity, stereoregularity of the hydrophobic components within the block copolymer, and the ionization of the pH functional groups in the copolymer, which depends on the environmental pH. Degradation of the triblock and pentablock copolymers at 37 °C (pH 7.4), and at 0 °C and 5 °C both at pH 8.0, was investigated. It was demonstrated here using the in vitro test method, that the anticancer agent paclitaxel (PTX) could be loaded and released by the pH and temperature sensitive OSM–PCGA–PEG–PCGA–OSM block copolymer, such that this could be used as a suitable matrix for subcutaneous injection in drug delivery systems.

PH- and temperature-sensitive, injectable, biodegradable block copolymer hydrogels as carriers for paclitaxel

Paclitaxel (PTX) was loaded into synthetic pH/ T-sensitive block copolymer (OSM–PCLA–PEG–PCLA–OSM) solution with various concentrations. The phase diagram of PTX-loaded block copolymer solution shifted to lower temperature region compared to net block copolymer because of the salting-out effect of PTX. Release profiles of PTX showed sustained manner regardless of loading amount of PTX. To evaluate anti-tumor effect of PTX-loaded block copolymer, solutions were injected subcutaneously to tumor-bearing mice and TUNEL assay examined. PTX-loaded block copolymer hydrogel for in vivo use showed good anti-tumor effect for 2 weeks and induced strong apoptosis in tumor tissue. Therefore, we conclude OSM–PCLA–PEG–PCLA–OSM block copolymer as an effective injectable carrier of PTX.