Injectable Hydrogel–Microsphere Construct with Sequential Degradation for Locally Synergistic Chemotherapy

Zheng, Yuhao; Cheng, Yilong; Chen, Jinjin; Ding, Jianxun; Li, Mingqiang; Li, Chen; Wang, Jincheng; Chen, Xuesi

doi:10.1021/acsami.6b15245

Cited by 96 publications

(69 citation statements)

References 30 publications

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“…Recently, biodegradable multilayered polymer particles consisting of two or more concentric layers that can be designed individually to encapsulate and release multiple actives at desirable rates, have garnered much attention among researchers especially in the area of drug delivery . Such multilayered structures with rationally designed layer properties offer multiple advantages over single layered particles like suppression of initial burst, ability to provide different kinds of release profiles for multiple drugs encapsulated in them, ability to deliver multiple drugs without having drug–drug interactions, and so forth.…”

Section: Introductionmentioning

confidence: 99%

New insight into the mechanism of formation of dual actives loaded multilayered polymeric particles and their application in food preservation

Biswal¹,

Saha²

2019

J of Applied Polymer Sci

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This study provides an insight about the mechanism of formation of tri‐layered (instead of bilayers) particles originated from two biodegradable polymers by emulsion solvent evaporation method. It was also demonstrated how layer configurations of tri‐layered particles composed of poly(l‐lactide) (PLLA) and poly(d,l‐lactide‐co‐glycolide) (PLGA), can be changed from kinetically trapped to thermodynamically favorable structures (dictated by spreading coefficient theory) by tweaking several solution parameters. Layer switching, core, and shell thickness manipulation can also be achieved. Interestingly, among the various configurations, tri‐layered particles made with PLGA of intermediate viscosity and PLLA of high viscosity were found to provide controlled and sustainable release profiles for dual actives such as antibacterial (benzoic acid) and antioxidant (tocopherol) with appreciably high release rates. The dual activity of these particles was tested by incorporating them in chicken broth medium and found to provide excellent antibacterial as well as antioxidant activity for extended period of time (>20 days). © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48009.

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Section: Introductionmentioning

confidence: 99%

New insight into the mechanism of formation of dual actives loaded multilayered polymeric particles and their application in food preservation

Biswal¹,

Saha²

2019

J of Applied Polymer Sci

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“…The release profiles of BUP from MS/BUP were determined by an immediate release method 36 . Briefly, the MS/BUP powder (74.0 mg) was added to 3.0 mL of PBS without or with 2.0 mg mL -1 of elastase.…”

Section: Methodsmentioning

confidence: 99%

Precision-guided long-acting analgesia by hydrogel-immobilized bupivacaine-loaded microsphere

Zhang¹,

Cong²,

Xu³

et al. 2018

Theranostics

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Peripheral nerve blockade (PNB) is a conventional strategy for the management of acute postoperative pain. However, the short duration of the associated analgesia and the potential systemic toxicity due to the low molecular weights of local anesthetics limit their application.Methods: An in situ forming injectable Gel-microsphere (Gel-MS) system consisting of PLGA-PEG-PLGA Gel (Gel) and Gel-immobilized bupivacaine-loaded microsphere (MS/BUP) was prepared for precision-guided long-acting analgesia. A series of in vitro characterizations, such as scanning electron microscopy, rheology analysis, confocal laser scanning microscopy, drug release, and erosion and degradation, were carried out. After that, the in vivo analgesia effect of the Gel-MS system, the immobilization effect of Gel on the MS, and biocompatibility of the system were evaluated using a sciatic nerve block model.Results: The BUP release from the Gel-MS system was regulated by both the inner MS and the outer Gel matrix, demonstrating sustained BUP release in vitro for several days without an initial burst release. More importantly, incorporation of the Gel immobilized the MS and hindered the diffusion of MS from the injection site because of its in situ property, which contributed to a high local drug concentration and prevented systemic side effects. In vivo, a single injection of Gel-MS/BUP allowed rats to maintain sensory and motor blockade significantly longer than treatment with MS/BUP (P < 0.01) or BUP-loaded Gel (Gel-BUP, P < 0.01). Histopathological results demonstrated the excellent biodegradability and biocompatibility of the Gel-MS system without neurotoxicity.Conclusion: This precision-guided long-acting analgesia, which provides an in situ and sustained release of BUP, is a promising strategy for long-acting analgesia, and could represent a potential alternative for clinical pain management.

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“…Two-dimensional nanopatterning by means of block copolymer micelle nanolithography (BCML) provides an elegant way to gain control over the density of immobilized molecules (Altrock et al, 2012;Platzman et al, 2013). On the one hand, loading block copolymer-based micelles can be applied for controlled drug delivery applications (Zheng et al, 2017;Zhang et al, 2018a,b), while on the other hand-in case of BCML-it allows also for the decoration of surfaces with gold nanoparticles (GNPs) in a hexagonal manner with well-defined interparticle distances. The subsequent transfer of the nanoparticles into the hydrogel followed by a further particle functionalization equips the biomaterial with the desired chemical functionality.…”

Section: Introductionmentioning

confidence: 99%

Nanostructured Bifunctional Hydrogels as Potential Instructing Platform for Hematopoietic Stem Cell Differentiation

et al. 2019

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Hematopoietic stem cells (HSCs) are blood forming cells which possess the ability to differentiate into all types of blood cells. T cells are one important cell type HSCs can differentiate into, via corresponding progenitor cells. T cells are part of the adaptive immune system as they mediate cellular immune responses. Due to this crucial function, in vitro differentiated T cells are the subject of current studies in the biomedical field in terms of cell transplantation. Studies show that the density of the immobilized Notch ligand Delta-like 1 (DLL1) presented in HSCs' environment can stimulate their differentiation toward T cells. The development of reliable synthetic cell culture systems presenting variable densities of DLL1 is promising for the future expansion of T cells' clinical applications. Here we introduce bifunctional polyethylene glycol-based (PEG-based) hydrogels as a potential instructing platform for the differentiation of human hematopoietic stem and progenitor cells (HSPCs) to T cells. PEG hydrogels bearing the cell adhesion supporting motif RGD (arginyl-glycyl-aspartic acid) were synthesized by UV-light induced radical copolymerization of PEG diacrylate and RGD modified PEG acrylate. The hydrogels were furthermore nanostructured by incorporation of gold nanoparticle arrays that were produced by block copolymer micelle nanolithography (BCML). BCML allows for the decoration of surfaces with gold nanoparticles in a hexagonal manner with well-defined interparticle distances. To determine the impact of DLL1 density on the cell differentiation, hydrogels with particle distances of ∼40 and 90 nm were synthesized and the gold nanoparticles were functionalized with DLL1. After 27 days in culture, HSPCs showed an unphysiological differentiation status and, therefore, the differentiation was evaluated as atypical T lymphoid differentiation. Cluster of differentiation (CD) 4 was the only tested T cell marker which was expressed clearly in all samples. Thus, although the applied nanopatterned hydrogels affected two important signaling pathways (integrins and Notch) for T cell differentiation, it appears that more functionalities that control T cell differentiation in nature need to be considered for achieving fully synthetic in vitro T cell differentiation strategies.

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Injectable Hydrogel–Microsphere Construct with Sequential Degradation for Locally Synergistic Chemotherapy

Cited by 96 publications

References 30 publications

New insight into the mechanism of formation of dual actives loaded multilayered polymeric particles and their application in food preservation

New insight into the mechanism of formation of dual actives loaded multilayered polymeric particles and their application in food preservation

Precision-guided long-acting analgesia by hydrogel-immobilized bupivacaine-loaded microsphere

Nanostructured Bifunctional Hydrogels as Potential Instructing Platform for Hematopoietic Stem Cell Differentiation

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