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Effect of Process Parameters on the Initial Burst Release of Protein-Loaded Alginate Nanospheres.

ABSTRACT: The controlled release or delivery of proteins encapsulated in micro/nanospheres is an emerging strategy in regenerative medicine. For this, micro/nanospheres made from alginate have drawn considerable attention for the use as a protein delivery device because of their mild fabrication process, inert nature, non-toxicity and biocompatibility. Though promising, one key issue associated with using alginate micro/nanospheres is the burst release of encapsulated protein at the beginning of the release, which may be responsible for exerting toxic side effects and poor efficiency of the delivery device. To address this issue, this study aimed to investigate the effect of process parameters of fabricating protein-loaded alginate nanospheres on the initial burst release. The alginate nanospheres were prepared via a combination of water-in-oil emulsification and the external gelation method and loaded with bovine serum albumin (BSA) as a model protein. The examined process parameters included alginate concentration, ionic cross-linking time and drying time. Once fabricated, the nanospheres were then subjected to the examination of BSA release, as well as the characterization of their morphology, size, and encapsulation efficiency. Our results revealed that by properly adjusting the process parameters, the initial burst release can be reduced by 13%. Taken together, our study demonstrates that regulating process parameters of fabricating alginate nanospheres is a possible means to reduce the initial burst release.

SUBMITTER: Yasmin F

PROVIDER: S-EPMC6787618 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Effect of Process Parameters on the Initial Burst Release of Protein-Loaded Alginate Nanospheres.

Yasmin Farhana F Chen Xiongbiao X Eames B. Frank BF

Journal of functional biomaterials 20190916 3

The controlled release or delivery of proteins encapsulated in micro/nanospheres is an emerging strategy in regenerative medicine. For this, micro/nanospheres made from alginate have drawn considerable attention for the use as a protein delivery device because of their mild fabrication process, inert nature, non-toxicity and biocompatibility. Though promising, one key issue associated with using alginate micro/nanospheres is the burst release of encapsulated protein at the beginning of the relea ...[more]

PMID: 31527490

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Project description:BackgroundParticulates incorporating DNA are promising vehicles for gene delivery, with the ability to protect DNA and provide for controlled, localized, and sustained release and transfection. Zein, a hydrophobic protein from corn, is biocompatible and has properties that make it a promising candidate material for particulate delivery, including its ability to form nanospheres through coacervation and its insolubility under physiological conditions, making it capable of sustained release of encapsulated compounds. Due to the promise of this natural biomaterial for drug delivery, the objective of this study was to formulate zein nanospheres encapsulating DNA as the therapeutic compound, and to characterize size, charge, sustained release, cell cytotoxicity and cellular internalization of these particles.ResultsZein nanospheres encapsulating DNA were fabricated using a coacervation technique, without the use of harsh solvents or temperatures, resulting in the preservation of DNA integrity and particles with diameters that ranged from 157.8 ± 3.9 nm to 396.8 ± 16.1 nm, depending on zein to DNA ratio. DNA encapsulation efficiencies were maximized to 65.3 ± 1.9% with a maximum loading of 6.1 ± 0.2 mg DNA/g zein. The spheres protected encapsulated DNA from DNase I degradation and exhibited sustained plasmid release for at least 7 days, with minimal burst during the initial phase of release. Zein/DNA nanospheres demonstrated robust biocompatibility, cellular association, and internalization.ConclusionsThis study represents the first report on the formation of zein particles encapsulating plasmid DNA, using simple fabrication techniques resulting in preservation of plasmid integrity and tunable sizes. DNA encapsulation efficiencies were maximized to acceptable levels at higher zein to DNA ratios, while loading was comparable to that of other hydrophilic compounds encapsulated in zein and that of DNA incorporated into PLGA nano- and microspheres. The hydrophobic nature of zein resulted in spheres capable of sustained release of plasmid DNA. Zein particles may be an excellent potential tool for the delivery of DNA with the ability to be fine-tuned for specific applications including oral gene delivery, intramuscular delivery, and in the fabrication of tissue engineering scaffolds.

Project description:Streptococcus agalactiae, or group B Streptococcus (GBS), is a common perinatal pathogen. GBS colonization of the vaginal mucosa during pregnancy is a risk factor for invasive infection of the fetal membranes (chorioamnionitis) and its consequences such as membrane rupture, preterm labor, stillbirth, and neonatal sepsis. Placental macrophages, or Hofbauer cells, are fetally derived macrophages present within placental and fetal membrane tissues that perform vital functions for fetal and placental development, including supporting angiogenesis, tissue remodeling, and regulation of maternal-fetal tolerance. Although placental macrophages as tissue-resident innate phagocytes are likely to engage invasive bacteria such as GBS, there is limited information regarding how these cells respond to bacterial infection. Here, we demonstrate in vitro that placental macrophages release macrophage extracellular traps (METs) in response to bacterial infection. Placental macrophage METs contain proteins, including histones, myeloperoxidase, and neutrophil elastase similar to neutrophil extracellular traps, and are capable of killing GBS cells. MET release from these cells occurs by a process that depends on the production of reactive oxygen species. Placental macrophage METs also contain matrix metalloproteases that are released in response to GBS and could contribute to fetal membrane weakening during infection. MET structures were identified within human fetal membrane tissues infected ex vivo, suggesting that placental macrophages release METs in response to bacterial infection during chorioamnionitis.IMPORTANCE Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a common pathogen during pregnancy where infection can result in chorioamnionitis, preterm premature rupture of membranes (PPROM), preterm labor, stillbirth, and neonatal sepsis. Mechanisms by which GBS infection results in adverse pregnancy outcomes are still incompletely understood. This study evaluated interactions between GBS and placental macrophages. The data demonstrate that in response to infection, placental macrophages release extracellular traps capable of killing GBS. Additionally, this work establishes that proteins associated with extracellular trap fibers include several matrix metalloproteinases that have been associated with chorioamnionitis. In the context of pregnancy, placental macrophage responses to bacterial infection might have beneficial and adverse consequences, including protective effects against bacterial invasion, but they may also release important mediators of membrane breakdown that could contribute to membrane rupture or preterm labor.

Dataset Information

Effect of Process Parameters on the Initial Burst Release of Protein-Loaded Alginate Nanospheres.

Publications

Effect of Process Parameters on the Initial Burst Release of Protein-Loaded Alginate Nanospheres.

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