Temperature-Sensitive Poly(caprolactone-<i>co</i>-trimethylene carbonate)−Poly(ethylene glycol)−Poly(caprolactone-<i>co</i>-trimethylene carbonate) as in Situ Gel-Forming Biomaterial

Choi, Bo Gyu; Joo, Min Kyung; Han, Dong Keun; Sohn, Youn Soo; Jeong, Byeongmoon

doi:10.1021/ma800562s

Cited by 65 publications

(53 citation statements)

References 36 publications

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“…The crystallization of the PCL block is partially reduced by copolymerizing caprolactone with lactide or trimethylene carbonate. 14,15 Pluronics Are Still Attractive Thermogels Aside from the research on thermogelling polyesters of PLGA and PCL, multiblock copolymers of Pluronics have been designed to solve the short gel duration problem of Pluronics. The mutiblock Pluronics are connected by terephthalate, 2,5-dicarboxy terephthalate, and disulfide ( Figure 5).…”

Section: How To Shorten the Dissolution Timementioning

confidence: 99%

Biodegradable Thermogels

et al. 2011

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All living creatures respond to external stimuli. Similarly, some polymers undergo conformational changes in response to changes in temperature, pH, magnetic field, electrical field, or the wavelength of light. In one type of stimuli-responsive polymer, thermogel polymers, the polymer aqueous solution undergoes sol-to-gel transition as the temperature increases. Drugs or cells can be mixed into the polymer aqueous solution when it is in its lower viscosity solution state. After injection of the solution into a target site, heating prompts the formation of a hydrogel depot in situ, which can then act as a drug releasing system or a cell growing matrix. In this Account, we describe key materials developed in our laboratory for the construction of biodegradable thermogels. We particularly emphasize recently developed polypeptide-based materials where the secondary structure and nanoassembly play an important role in the determining the material properties. This Account will provide insights for controlling parameters, such as the sol-gel transition temperature, gel modulus, critical gel concentration, and degradability of the polymer, when designing a new thermogel system for a specific biomedical application. By varying the stereochemistry of amino acids in polypeptides, the molecular weight of hydrophobic/hydrophilic blocks, the composition of the polypeptides, the hydrophobic end-capping of the polypeptides, and the microsequences of a block copolymer, we have controlled the thermosensitivity and nanoassembly patterns of the polymers. We have investigated a series of thermogel biodegradable polymers. Polymers such as poly(lactic acid-co-glycolic acid), polycaprolactone, poly(trimethylene carbonate), polycyanoacrylate, sebacic ester, polypeptide were used as hydrophobic blocks, and poly(ethylene glycol) and poly(vinyl pyrrolidone) were used as hydrophilic blocks. To prepare a polymer sensitive to pH and temperature, carboxylic acid or amine groups were introduced along the polymer backbone. The sol-gel transition mechanism involves changes in the secondary structures of the hydrophobic polypeptide and in the conformation of the hydrophilic block. The polypeptide copolymers were stable in the phosphate buffered saline, but the presence of proteolytic enzymes such as elastase, cathepsin B, cathepsin C, and matrix metallopreoteinase accelerated their degradation. We also describe several biomedical applications of biogradable thermogel polymers. One subcutaneous injection of the insulin formulation of thermogel polypeptide copolymers in diabetic rats provided hypoglycemic efficacy for more than 16 days. The thermogels also provided a compatible microenvironment for chondrocytes, and these cells produced biomarkers for articular cartilage such as sulfated glucoaminoglycan (sGAG) and type II collagen. The thermogels were also used as a fixing agent for in situ cell imaging, and cellular activities such as endocytosis were observed by live cell microscopy.

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Section: How To Shorten the Dissolution Timementioning

confidence: 99%

Biodegradable Thermogels

et al. 2011

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“…Thus, gel duration of PEG–PCL–PEG thermogel could be controlled by designing a PEG–PCL–PEG with an oxalate bond at the middle of the triblock copolymer. Previously, gel duration of PCL was controlled by copolymerization of caprolactone and lactide or glycolide . However, the copolymerization led to loss of crystallinity of PCL, which provided powder morphology of the polymer .…”

Section: Resultsmentioning

confidence: 99%

ROS‐Sensitive Degradable PEG–PCL–PEG Micellar Thermogel

Lee

Jeong

2019

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A reactive oxygen species (ROS)‐sensitive degradable polymer would be a promising material in designing a disease‐responsive system or accelerating degradation of polymers with slow hydrolysis kinetics. Here, a thermogelling poly(ethylene glycol)–polycaprolactone–poly(ethylene glycol) (PEG–PCL–PEG or EG12–CL20–EG12) triblock copolymer with an oxalate group at the middle of the polymer is reported. The polymers form micelles with an average size of 100 nm in water. Thermogelation is observed in a concentration range of 8.0−37.0 wt%. In particular, the aqueous PEG–PCL–PEG triblock copolymer solutions are in a gel state at 37 °C in a concentration range of 25.0–37.0 wt%, whereas the aqueous PEG–PCL diblock copolymer solutions are in a sol state in the same concentration range at 37 °C. Thus, the gel depot could dissolve out once degradation of the triblock copolymers occurs at the oxalate group as confirmed by the in vitro experiment. In vivo gel formation is confirmed by injecting an aqueous PEG–PCL–PEG solution (36.0 wt%) into the subcutaneous layer of rats. The gel completely disappears in 21 d. A model polypeptide drug (cyclosporine A) is released over 21 d from the in situ formed gel. The micelle‐based thermogel of PEG–PCL–PEG with ROS‐triggering degradability is a promising injectable material for biomedical applications.

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“…Calcium ammoniate, HCl/Et 2 A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 5 The morphologies of the self-assemblies in PEG-PCL diblock copolymers aqueous solution were highly dependent on the length of the building blocks. For example, Xu and his coworkers reported that the micellar morphology of PEG-PCL block copolymers in water can be regulated by crystallization temperatures.…”

Section: Diblock Copolymers and Their Self-assembliesmentioning

confidence: 99%

“…Such structure and functionality tailoring of PCL produces desired polymers with superior properties for a wide variety of applications including targeted drug delivery, sustained gene delivery, injectables and three dimensional (3D) cell encapsulation in tissue engineering. [1][2][3][4][5][6][7][8][9][10] In this review, the most intensively studied PCL based amphiphilic block copolymers are discussed in terms of their different architectures and various self-…”

Section: Introductionmentioning

confidence: 99%