Development of a Biocompatible PLGA Polymers Capable to Release Thrombolytic Enzyme Prourokinase

Kaplan, M. A.; Sergienko, K. V.; Колмакова, А. А.; Konushkin, S. V.; Баикин, А. С.; Колмаков, А. Г.; Sevostyanov, M. A.; Куликов, А. В.; Иванов, В. Э.; Belosludtsev, Konstantin N.; Antipov, S.S.; Volkov, Mikhail Yu; Shusharina, Natalya N.; Karaduleva, E. V.; Козлов, В. А.; Simakin, Alexander V.; Gudkov, Sergey V.

doi:10.1080/09205063.2020.1760699

Cited by 17 publications

(9 citation statements)

References 35 publications

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“…Microscopic assay of the samples was carried out with imaging system based on Leica DMI6000 (Leica, Berlin, Germany). On the surface of each sample at least 500 cells were counted for analysis [35].…”

Section: Cell Culturementioning

confidence: 99%

New Organosilicon Composite Based on Borosiloxane and Zinc Oxide Nanoparticles Inhibits Bacterial Growth, but Does Not Have a Toxic Effect on the Development of Animal Eukaryotic Cells

et al. 2021

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The present study a comprehensive analysis of the antibacterial properties of a composite material based on borosiloxane and zinc oxide nanoparticles (ZnO NPs). The effect of the polymer matrix and ZnO NPs on the generation of reactive oxygen species, hydroxyl radicals, and long-lived oxidized forms of biomolecules has been studied. All variants of the composites significantly inhibited the division of E. coli bacteria and caused them to detach from the substrate. It was revealed that the surfaces of a composite material based on borosiloxane and ZnO NPs do not inhibit the growth and division of mammalians cells. It is shown in the work that the positive effect of the incorporation of ZnO NPs into borosiloxane can reach 100% or more, provided that the viscoelastic properties of borosiloxane with nanoparticles are retained.

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Section: Cell Culturementioning

confidence: 99%

New Organosilicon Composite Based on Borosiloxane and Zinc Oxide Nanoparticles Inhibits Bacterial Growth, but Does Not Have a Toxic Effect on the Development of Animal Eukaryotic Cells

et al. 2021

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“…Pharmaceutics, regardless of their molar weight, can be loaded into PLGA drug delivery systems and consequently released from the matrix in a controlled manner. Consequently, a wide variety of active compounds can be used as payload of PLGA based drug delivery systems ranging from small molecules such as anti-tumour drugs with molar weight 0.5 kDa [15] to proteins and enzymes with molar mass up to 50 kDa [16,17]. The drug release profile of PLGA based drug delivery systems is usually characterized by the initial burst of a loaded drug followed by zero order kinetics release [18].…”

Section: Introductionmentioning

confidence: 99%

PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery System

et al. 2021

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Macrophages possess an innate ability to scavenge heterogenous objects from the systemic circulation and to regulate inflammatory diseases in various organs via cytokine production. That makes them attractive targets for nanomedicine-based therapeutic approaches to inflammatory diseases. In the present study, we have prepared several different poly(lactic-co-glycolic acid) (PLGA) polymer nanospheres for macrophage-targeted drug delivery using both nanoprecipitation and emulsification solvent evaporation methods. Two experimental linear PLGA polymers with relatively low molar weight, one experimental branched PLGA with unique star-like molecular architecture, and a commercially available PLGA, were used for nanosphere formulation and compared to their macrophage uptake capacity. The nanosphere formulations labelled with loaded fluorescent dye Rhodamine B were further tested in mouse bone marrow-derived macrophages and in hepatocyte cell lines AML-12, HepG2. We found that nanospheres larger than 100 nm prepared using nanoprecipitation significantly enhanced distribution of fluorescent dye selectively into macrophages. No effects of nanospheres on cellular viability were observed. Additionally, no significant proinflammatory effect after macrophage exposure to nanospheres was detected as assessed by a determination of proinflammatory cytokines Il-1β and Tnfα mRNA. All experimental PLGA nanoformulations surpassed the nanospheres obtained with the commercially available polymer taken as a control in their capacity as macrophage-specific carriers.

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“…In particular, Poly(D,L-lactideco-glycolide) (PLGA), a U.S. Food and Drug Administration (FDA)-approved polymer that can self-assemble into NPs has been of high interest [37][38][39]. This is because it is capable of encapsulating large molecules such as proteins and enzymes [40][41][42][43][44] and has also been demonstrated to have the capacity to transport large cargo across the BBB by adding targeting ligands [2,[45][46][47]. This makes PLGA NPs a prime option to overcome many of these barriers for ERT treatment.…”

Section: Introductionmentioning

confidence: 99%

Tween® Preserves Enzyme Activity and Stability in PLGA Nanoparticles

et al. 2021

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Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the Tween® polysorbate series, have demonstrated enzyme activity protection but are often used uncontrolled without optimization. Here, poly(lactic-co-glycolic) acid (PLGA) NPs loaded with β-glucosidase (β-Glu) solutions containing Tween® 20, 60, or 80 were compared. Mixing the enzyme with Tween® pre-formulation had no effect on particle size or physical characteristics, but increased the amount of enzyme loaded. More importantly, NPs made with Tween® 20:enzyme solutions maintained significantly higher enzyme activity. Therefore, Tween® 20:enzyme solutions ranging from 60:1 to 2419:1 mol:mol were further analyzed. Isothermal titration calorimetry analysis demonstrated low affinity and unquantifiable binding between Tween® 20 and β-Glu. Incorporating these solutions in NPs showed no effect on size, zeta potential, or morphology. The amount of enzyme and Tween® 20 in the NPs was constant for all samples, but a trend towards higher activity with higher molar rapports of Tween® 20:β-Glu was observed. Finally, a burst release from NPs in the first hour with Tween®:β-Glu solutions was the same as free enzyme, but the enzyme remained active longer in solution. These results highlight the importance of stabilizers during NP formulation and how optimizing their use to stabilize an enzyme can help researchers design more efficient and effective enzyme loaded NPs.

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Development of a Biocompatible PLGA Polymers Capable to Release Thrombolytic Enzyme Prourokinase

Cited by 17 publications

References 35 publications

New Organosilicon Composite Based on Borosiloxane and Zinc Oxide Nanoparticles Inhibits Bacterial Growth, but Does Not Have a Toxic Effect on the Development of Animal Eukaryotic Cells

New Organosilicon Composite Based on Borosiloxane and Zinc Oxide Nanoparticles Inhibits Bacterial Growth, but Does Not Have a Toxic Effect on the Development of Animal Eukaryotic Cells

PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery System

Tween® Preserves Enzyme Activity and Stability in PLGA Nanoparticles

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