Camptothecine encapsulated composite drug delivery system for colorectal peritoneal carcinomatosis therapy: Biodegradable microsphere in thermosensitive hydrogel

Liu, Lei; Wu, Qinjie; Ma, Xuelei; Xiong, Dake; Gong, Changyang; Zhang, Qian; Zhao, Xia; Wei, Yuquan

doi:10.1016/j.colsurfb.2013.01.047

Cited by 33 publications

(29 citation statements)

References 28 publications

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“…DOX and CPT were paired to demonstrate the co-delivery synergistic effect of two chemotherapeutical drugs in the same vehicle. DOX can bind to DNA by intercalation and motivates a series of biochemical events including apoptosis in tumor cells, and CPT can stabilize the normally transient cleavable DNA-topo I complex and forms an enzyme-drug-DNA ternary cleavable complex [36][37][38]. The collision of the replication fork with a cleaved strand of DNA causes an irreversible arrest of the replication fork, However, when the microparticles are loaded with either DOX or CPT, more than 50% HCT116 cells and 60% HepG2 cells are killed (Figs S8 and S9).…”

Section: Resultsmentioning

confidence: 99%

Composite core-shell microparticles from microfluidics for synergistic drug delivery

Yan

et al. 2017

Sci. China Mater.

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Microparticles have a demonstrated value for drug delivery systems. The attempts to develop this technology focus on the generation of featured microparticles for improving the function of the systems. Here, we present a new type of microparticles with gelatin methacrylate (GelMa) cores and poly(L-lactide-co-glycolide) (PLGA) shells for synergistic and sustained drug delivery applications. The microparticles were fabricated by using GelMa aqueous solution and PLGA oil solution as the raw materials of the microfluidic double emulsion templates, in which hydrophilic and hydrophobic actives, such as doxorubicin hydrochloride (DOX, hydrophilic) and camptothecine (CPT, hydrophobic), could be loaded respectively. As the inner cores were polymerized in the microfluidics when the double emulsions were formed, the hydrophilic actives could be trapped in the cores with high efficiency, and the rupture or fusion of the cores could be avoided during the solidification of the microparticle shells with other actives. The size and component of the microparticles can be easily and precisely adjusted by manipulating the flow solutions during the microfluidic emulsification. Because of the solid structure of the resultant microparticles, the encapsulated actives were released from the delivery systems only with the degradation of the biopolymer layers, and thus the burst release of the actives was avoided. These features of the microparticles make them ideal for drug delivery applications.

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Section: Resultsmentioning

confidence: 99%

Composite core-shell microparticles from microfluidics for synergistic drug delivery

Yan

et al. 2017

Sci. China Mater.

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“…C57 mice were transplanted with fluorescein isothiocyanatelabeled melanoma or LLC leukemia cells via intravenous injection, and thermogelling dispersions of polymer nanoparticles loaded with erythropoietin (600 IU/ ml) in the presence or absence of doxorubicine (300 μg/ml) and paclitaxel (30 mg/ml) showed that such cancer cell traps can eradicate circulating cancer cells at the implant sites (>95% elimination in 7 days). Gel microspheres have been described in the literature in the context of local delivery of chemotherapy drugs [42], but not as semi-active cell traps.…”

Section: Treatment Of Pain By Inhibition Of Usp5 De-ubiquitinasementioning

confidence: 99%

Patent Highlights

Mucke¹

2014

Pharm. Pat. Anal.

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The discoidin domain-containing receptor 2 (DDR2; also CCK-2, tyro-10, or CD167b) is a receptor tyrosine kinase that is activated upon collagen binding in a delayed but sustained fashion. It is an important regulator of neutrophil chemotaxis in 3D collagen matrices [1]. In osteoarthritis, joint cartilage injury or loss of growth factor sensitivity of articular chondrocytes results in a breakdown of the pericellular collagen VI-rich matrix, exposing the DDR2 receptor on chondrocytes to collagen II fibers or fragments and activating it, which results in the release of cytokines and degradation by proteases. Compounds of the present invention bearing phenyl or hetero-aromatic rings in the R3 position are strong and selective inhibitors of DDR2. Its expression is also associated with invasiveness of carcinomas and inferior prognosis [2], and patenting for this target has focused on solid tumors. Related ureidomethyl-phenoxypyridines and phenyl-3-[4-(pyridin-4-yloxy)-benzyl]ureas have been disclosed as Tie-2 and cRaf kinase inhibitors in WO/2004/037789 and WO/2006/042599, and as Aurora and RON kinase inhibitors in WO/2011/017142; all in the context of cancer. Note that actinomycin D is also an inhibitor of DDR2 activation by type I collagen; however, its IC 50 in HEK-293 human embryonic kidney cells, 9 μM [3], is 1-2 orders of magnitude higher than that for the compounds presented here.

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“…Transforming growth factor-β1 (TGF-β1) plays a significant role in various processes associated with chondrogenesis, such as chondrocyte growth and differentiation and enhancement of the biomechanical properties of neocartilage 37 – 39 . Local drug delivery systems (LDDS) have long been investigated owing to their potential for the transport of drugs or bioactive molecules to target loci and their sustained release, thereby overcoming the shortcomings of conventional methods by reducing adverse systemic reactions and enhancing therapeutic effects 40 – 44 . An optimal LDDS should release drugs sustainably, with its carrier being non-toxic, biodegradable, and biocompatible.…”

Section: Introductionmentioning

confidence: 99%

Injectable and thermosensitive TGF-β1-loaded PCEC hydrogel system for in vivo cartilage repair

Zhou

Guo

et al. 2017

Sci Rep

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Chondral defects pose a great challenge for clinicians to manage owing to the limited capacity for self-healing. Various traditional approaches have been adopted for the repair of these defects with unsatisfactory results. Cartilage tissue engineering techniques have emerged as promising strategies to enhance regeneration and overcome these traditional shortcomings. The cell-homing based technique is considered the most promising owing to its unique advantages. Thermosensitive hydrogels have been applied as scaffolds for biomedical applications with smart sol–gel response for altering environmental temperature. Transforming growth factor (TGF)-β1 is considered to be capable of promoting chondrogenesis. In this study, a novel TGF-β1-loaded poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCEC) hydrogel was fabricated using simple procedures. Hydrogel characterization, rheological testing, component analysis, and assessment of sol–gel transition, in vitro degradation, and TGF-β1 release confirmed that this material possesses a porous microstructure with favorable injectability and sustained drug release. Full-thickness cartilage defects were induced on rat knees for in vivo cartilage repair for eight weeks. Micro-CT and histological evaluation provided further evidence of the optimal capacity of this novel hydrogel for cartilage regeneration with respect to that of other methods. Moreover, our results demonstrated that the cell-free hydrogel is thermosensitive, injectable, biodegradable, and capable of in vivo cartilage repair and possesses high potential and benefits for acellular cartilage tissue engineering and clinical application in the future.

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Camptothecine encapsulated composite drug delivery system for colorectal peritoneal carcinomatosis therapy: Biodegradable microsphere in thermosensitive hydrogel

Cited by 33 publications

References 28 publications

Composite core-shell microparticles from microfluidics for synergistic drug delivery

Composite core-shell microparticles from microfluidics for synergistic drug delivery

Patent Highlights

Injectable and thermosensitive TGF-β1-loaded PCEC hydrogel system for in vivo cartilage repair

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