Biodegradable insulin-loaded PLGA microspheres fabricated by three different emulsification techniques: Investigation for cartilage tissue engineering

Andreas, Kristin; Zehbe, Rolf; Kazubek, Maja; Grzeschik, Karolina; Sternberg, Nadine; Bäumler, Hans; Schubert, H.; Sittinger, Michael; Ringe, Jochen

doi:10.1016/j.actbio.2010.12.014

Cited by 79 publications

(55 citation statements)

References 74 publications

(75 reference statements)

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“…Biodegradable delivery devices that release bioactive insulin in a sustained manner are essential for the engineering of cartilage because insulin has a low half-life in vivo and is unstable in the presence of cartilage (15,16) . Insulin-loaded PLGA microspheres were prepared by Andreas et al (2) and employed in a high density three-dimensional (3D) in vitro cartilage engineering model. PLGA microspheres prepared by the w/o/w procedure showed sustained release of structurally intact and biologically active insulin that promoted the formation of cartilage-specific extracellular matrix (ECM) and thus represented a potent delivery device for application (2) .…”

Section: Plga Based Drug Delivery Devices For Cartilage Tissue Enginementioning

confidence: 99%

“…Insulin-loaded PLGA microspheres were prepared by Andreas et al (2) and employed in a high density three-dimensional (3D) in vitro cartilage engineering model. PLGA microspheres prepared by the w/o/w procedure showed sustained release of structurally intact and biologically active insulin that promoted the formation of cartilage-specific extracellular matrix (ECM) and thus represented a potent delivery device for application (2) . Apart from microspheres, PLGA scaffolds were also used for cartilage tissue engineering.…”

Section: Plga Based Drug Delivery Devices For Cartilage Tissue Enginementioning

confidence: 99%

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Poly(Lactic-Co-Glycolic Acid) Based Drug Delivery Devices For Tissue Engineering And Regenerative Medicine

Kerımoğlu¹,

Alarçin²

2012

Ankem Derg

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Section: Plga Based Drug Delivery Devices For Cartilage Tissue Enginementioning

confidence: 99%

Section: Plga Based Drug Delivery Devices For Cartilage Tissue Enginementioning

confidence: 99%

Poly(Lactic-Co-Glycolic Acid) Based Drug Delivery Devices For Tissue Engineering And Regenerative Medicine

Kerımoğlu¹,

Alarçin²

2012

Ankem Derg

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show abstract

“…[32][33][34] In addition, the shear used for the emulsification can also contribute to insulin denaturation. 35 Hence, maintaining the native conformation of insulin during the encapsulation process is highly important, which otherwise may lead to protein aggregation and immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation

Lopes¹,

Abrahim-Vieira²,

Oliveira³

et al. 2015

IJN

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Alginate–dextran sulfate-based particles obtained by emulsification/internal gelation technology can be considered suitable carriers for oral insulin delivery. A rational study focused on the emulsification and particle recovery steps was developed in order to reduce particles to the nanosize range while keeping insulin bioactivity. There was a decrease in size when ultrasonication was used during emulsification, which was more pronounced when a cosurfactant was added. Ultrasonication add-on after particle recovery decreased aggregation and led to a narrower nanoscale particle-size distribution. Insulin encapsulation efficiency was 99.3%±0.5%, attributed to the strong pH-stabilizing electrostatic effect between insulin and nanoparticle matrix polymers. Interactions between these polymers and insulin were predicted using molecular modeling studies through quantum mechanics calculations that allowed for prediction of the interaction model. In vitro release studies indicated well-preserved integrity of nanoparticles in simulated gastric fluid. Circular dichroism spectroscopy proved conformational stability of insulin and Fourier transform infrared spectroscopy technique showed rearrangements of insulin structure during processing. Moreover, in vivo biological activity in diabetic rats revealed no statistical difference when compared to nonencapsulated insulin, demonstrating retention of insulin activity. Our results demonstrate that alginate–dextran sulfate-based nanoparticles efficiently stabilize the loaded protein structure, presenting good physical properties for oral delivery of insulin.

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“…Drug loading rate (wt%) was the percent of pBMP-2 entrapped in the microspheres in the total amount of PLGA@pBMP-2/PEI. 22 The amount of pBMP-2 in the microspheres was determined by subtracting the amount of pBMP-2 recovered in the wash solutions from the initial amount of pBMP-2 added.…”

Section: Characteristics Of Plga@pbmp-2/pei Particle Morphologymentioning

confidence: 99%

Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo

Qiao

Zhang²,

Jin³

et al. 2013

IJN

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Abstract:Repair of large bone defects is a major challenge, requiring sustained stimulation to continually promote bone formation locally. Bone morphogenetic protein 2 (BMP-2) plays an important role in bone development. In an attempt to overcome this difficulty of bone repair, we created a delivery system to slowly release human BMP-2 cDNA plasmid locally, efficiently transfecting local target cells and secreting functional human BMP-2 protein. For transfection, we used polyethylenimine (PEI) to create pBMP-2/PEI nanoparticles, and to ensure slow release we used poly(lactic-co-glycolic acid) (PLGA) to create microsphere encapsulated pBMP-2/ PEI nanoparticles, PLGA@pBMP-2/PEI. We demonstrated that pBMP-2/PEI nanoparticles could slowly release from the PLGA@pBMP-2/PEI microspheres for a long period of time. The 3-15 µm diameter of the PLGA@pBMP-2/PEI further supported this slow release ability of the PLGA@pBMP-2/PEI. In vitro transfection assays demonstrated that pBMP-2/PEI released from PLGA@pBMP-2/PEI could efficiently transfect MC3T3-E1 cells, causing MC3T3-E1 cells to secrete human BMP-2 protein, increase calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7 and I type collagen (COLL I), and finally induce MC3T3-E1 cell differentiation. Importantly, in vivo data from micro-computed tomography (micro-CT) and histological staining demonstrated that the human BMP-2 released from PLGA@pBMP-2/PEI had a long-term effect locally and efficiently promoted bone formation in the bone defect area compared to control animals. All our data suggest that our PLGA-nanoparticle delivery system efficiently and functionally delivers the human BMP-2 cDNA and has potential clinical application in the future after further modification.

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Biodegradable insulin-loaded PLGA microspheres fabricated by three different emulsification techniques: Investigation for cartilage tissue engineering

Cited by 79 publications

References 74 publications

Poly(Lactic-Co-Glycolic Acid) Based Drug Delivery Devices For Tissue Engineering And Regenerative Medicine

Poly(Lactic-Co-Glycolic Acid) Based Drug Delivery Devices For Tissue Engineering And Regenerative Medicine

Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation

Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo

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