Thermosensitive PEG–PCL–PEG Hydrogel Controlled Drug Delivery System: Sol–Gel–Sol Transition and In Vitro Drug Release Study

Gong, Chang Yang; Dong, Pengcheng; Shi, Shuai; Shao, Fu; Yang, Jin; Guo, Gang; Zhao, Xia; Wei, Yu Quan; Qian, Zhi

doi:10.1002/jps.21694

Cited by 71 publications

(48 citation statements)

References 38 publications

(54 reference statements)

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“…So far, both natural macromolecules like collagen, 15 chitosan, 16 gelatin, 17 alginate 18 and hyaluronic acid 19 and synthetic polymers such as poly(N-isopropylacrylamide) (PNIPAAm), 20 poly(ethylene glycol)/poly(lactic acid-co-glycolic acid) (PEG/PLGA) copolymers, 21 poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymers, 22 and Pluronic ® (PEO-PPO-PEO; BASF Corporation, Ludwigshafen, Germany), 23 or their combinations 24 have been utilized to produce injectable hydrogels. As one of the most widely used injectable hydrogels, PNIPAAm is a thermosensitive intelligent material which undergoes a reversible sol-gel transition around 32°C in an aqueous condition, converting from flowable solution to hydrogel when heated above its lower critical solution temperature (LCST).…”

Section: Introductionmentioning

confidence: 99%

Injectable hydrogel as stem cell scaffolds from the thermosensitive terpolymer of NIPAAm/AAc/HEMAPCL

Lian

Xiao²,

Bian³

et al. 2012

IJN

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A series of biodegradable thermosensitive copolymers was synthesized by free radical polymerization with N-isopropylacrylamide (NIPAAm), acrylic acid (AAc) and macromer 2-hydroxylethyl methacrylate-poly(ε-caprolactone) (HEMAPCL). The structure and composition of the obtained terpolymers were confirmed by proton nuclear magnetic resonance spectroscopy, while their molecular weight was measured using gel permeation chromatography. The copolymers were dissolved in phosphate-buffered saline (PBS) solution (pH = 7.4) with different concentrations to prepare hydrogels. The lower critical solution temperature (LCST), cloud point, and rheological property of the hydrogels were determined by differential scanning calorimetry, ultraviolet-visible spectrometry, and rotational rheometry, respectively. It was found that LCST of the hydrogel increased significantly with the increasing NIPAAm content, and hydrogel with higher AAc/HEMAPCL ratio exhibited better storage modulus, water content, and injectability. The hydrogels were formed by maintaining the copolymer solution at 37°C. The degradation experiment on the formed hydrogels was conducted in PBS solution for 2 weeks and demonstrated a less than 20% weight loss. Scanning electron microscopy was also used to study the morphology of the hydrogel. The copolymer with NIPAAm/AAc/HEMAPCL ratio of 88:9.6:2.4 was bioconjugated with type I collagen for the purpose of biocompatibility enhancement. In-vitro cytotoxicity of the hydrogels both with and without collagen was also addressed.

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Section: Introductionmentioning

confidence: 99%

Injectable hydrogel as stem cell scaffolds from the thermosensitive terpolymer of NIPAAm/AAc/HEMAPCL

Lian

Xiao²,

Bian³

et al. 2012

IJN

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“…33,34 Among these, thermal-sensitive hydrogels are the mostly extensively studied because they can be injected as a liquid with in situ gel formation at physiologic temperature. In previous studies, Fan et al 31 and Gong et al 35 have reported the PECE thermosensitive hydrogels, and they were proven to be injectable, biocompatible, and bioabsorbable. However, their studies were mainly focused on the use of hydrogels as a drug delivery system.…”

Section: Discussionmentioning

confidence: 99%

“…The 1 H-NMR result is in agreement with that reported by Gong et al, indicating that the PECE copolymer was prepared successfully. 35 The pure PECE copolymer had two strong characteristic peaks at 21.3° and 23.7°, indicating that this copolymer is only partly crystalline ( Figure 3C). Two peaks could be observed for the g-β-TCP/PECE and g-TTCP/PECE hydrogel composites, but their intensity was markedly decreased.…”

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confidence: 99%

Injectable thermosensitive hydrogel composite with surface-functionalized calcium phosphate as raw materials

Fan¹,

Deng²,

Zhou³

et al. 2014

IJN

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In this study, L-lactide was used to modify the tricalcium phosphate (β-TCP) and tetracalcium phosphate (TTCP) surface which can form functionalized poly(l-lactic acid) (PLLA)-grafted β-TCP (g-β-TCP) and PLLA-grafted TTCP (g-TTCP) particles. The g-β-TCP and g-TTCP obtained were incorporated into a PEG-PCL-PEG (PECE) matrix to prepare injectable thermosensitive hydrogel composites. The morphology of the hydrogel composites showed that the g-β-TCP and g-TTCP particles dispersed homogeneously into the polymer matrix, and each hydrogel composite had a three-dimensional network structure. Rheologic analysis showed that the composite had good thermosensitivity. Changes in calcium concentration and pH in simulated body fluid solutions confirmed the feasibility of surface-functionalized calcium phosphate for controlled release of calcium. All the results indicate that g-β-TCP/PECE and g-TTCP/PECE hydrogels might be a promising protocol for tissue engineering.

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“…Rejinold et al (2011) designed a highly stable curcuminloaded thermosensitive NP drug delivery system based on chitosan-g-poly(N-vinylcaprolactam) (TRC-Nps), which showed preferential cytotoxicity toward cancerous cells and seemed to be more beneficial when combined with hyperthermia. Gong et al (2009a) introduced a thermosensitive polyethylene glycol-poly("-caprolactone)-polyethylene glycol (PEG-PCL-PEG, PECE) hydrogel, which remains in the soluble phase at low temperatures (10 C) but forms a gel at body temperature upon injection. Thermosensitive PECE hydrogel has been used for the controlled delivery of anticancer drugs such as bFGF, honokiol and 5-Fu (Gong et al, 2009bFang et al, 2009;Wang et al, 2010).…”

Section: Thermosensitive Polymersmentioning

confidence: 99%

Classification of stimuli–responsive polymers as anticancer drug delivery systems

et al. 2014

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Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.

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Thermosensitive PEG–PCL–PEG Hydrogel Controlled Drug Delivery System: Sol–Gel–Sol Transition and In Vitro Drug Release Study

Cited by 71 publications

References 38 publications

Injectable hydrogel as stem cell scaffolds from the thermosensitive terpolymer of NIPAAm/AAc/HEMAPCL

Injectable hydrogel as stem cell scaffolds from the thermosensitive terpolymer of NIPAAm/AAc/HEMAPCL

Injectable thermosensitive hydrogel composite with surface-functionalized calcium phosphate as raw materials

Classification of stimuli–responsive polymers as anticancer drug delivery systems

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