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High Throughput Preparation of Poly(Lactic-Co-Glycolic Acid) Nanoparticles Using Fiber Fluidic Reactor.

ABSTRACT: Polymeric nanoparticles (NPs) have a variety of biomedical, biotechnology, agricultural and environmental applications. As such, a great need has risen for the fabrication of these NPs in large scales. In this study, we used a high throughput fiber reactor for the preparation of poly(lactic-co-glycolic acid) (PLGA) NPs via nanoprecipitation. The fiber reactor provided a high surface area for the controlled interaction of an organic phase containing the PLGA solution with an aqueous phase, containing poly(vinyl alcohol) (PVA) as a stabilizer. This interaction led to the self-assembly of the polymer into the form of NPs. We studied operational parameters to identify the factors that have the greatest influence on the properties of the resulting PLGA NPs. We found that the concentration of the PLGA solution is the factor that has the greatest effect on NP size, polydispersity index (PDI), and production rate. Increasing PLGA concentration increased NP sizes significantly, while at the same time decreasing the PDI value. The second factor that was found to affect NP properties was the concentration of PVA solution, which resulted in increased NP sizes and decreased production rates. Flowrates of the feed streams also affected NP size to a lesser extent, while changing the operational temperature did not change the product's features. In general, the results demonstrate that fiber reactors are a suitable method for the large-scale, continuous preparation of polymeric NPs suitable for biomedical applications.

SUBMITTER: Heshmati Aghda N

PROVIDER: S-EPMC7411994 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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High Throughput Preparation of Poly(Lactic-Co-Glycolic Acid) Nanoparticles Using Fiber Fluidic Reactor.

Heshmati Aghda Niloofar N Lara Emilio J EJ Patel Pulinkumar P Betancourt Tania T

Materials (Basel, Switzerland) 20200709 14

Polymeric nanoparticles (NPs) have a variety of biomedical, biotechnology, agricultural and environmental applications. As such, a great need has risen for the fabrication of these NPs in large scales. In this study, we used a high throughput fiber reactor for the preparation of poly(lactic-<i>co</i>-glycolic acid) (PLGA) NPs via nanoprecipitation. The fiber reactor provided a high surface area for the controlled interaction of an organic phase containing the PLGA solution with an aqueous phase, ...[more]

PMID: 32660141

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Project description:BackgroundNanoparticles exhibit distinct behaviours within the body, depending on their physicochemical properties and administration routes. However, in vivo behaviour of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, especially when administered nasally, remains unexplored; furthermore, there is a lack of comparative analysis of uptake efficiency among different administration routes. Therefore, here, we aimed to comprehensively investigate the real-time in vivo behaviour of PLGA nanoparticles across various administration routes. PLGA-NH2 nanoparticles of three sizes were synthesised using an oil-in-water single-emulsion method. We assessed their uptake by murine macrophage RAW264.7 cells using fluorescence microscopy. To enable real-time tracking, we conjugated p-SCN-Bn-deferoxamine to PLGA-NH2 nanoparticles and further radiolabelled them with 89Zr-oxalate before administration to mice via different routes. Nanoparticle internalisation by lung immune cells was monitored using fluorescence-activated cell sorting analysis.ResultsThe nanoparticle sizes were 294 ± 2.1 (small), 522.5 ± 5.58 (intermediate), and 850 ± 18.52 nm (large). Fluorescent labelling did not significantly alter the nanoparticle size and charge. The level of uptake of small and large nanoparticles by RAW264.7 cells was similar, with phagocytosis inhibition primarily reducing the internalisation of large particles. Positron emission tomography revealed that intranasal delivery resulted in the highest and most targeted pulmonary uptake, whereas intravenous administration led to accumulation mainly in the liver and spleen. Nasal delivery of large nanoparticles resulted in enhanced uptake by myeloid immune cells relative to lymphoid cells, whereas dendritic cell uptake initially peaked but declined over time.ConclusionsOur study provides valuable insights into advancing nanomedicine and drug delivery, with the potential for expanding the clinical applications of nanoparticles.

Project description:Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability.Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells.Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo.These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future studies should focus on enhancing the resistance to metabolic degradation and conversion of CUR to other metabolites, which may lead to novel discoveries regarding food function and disease prevention.

Dataset Information

High Throughput Preparation of Poly(Lactic-Co-Glycolic Acid) Nanoparticles Using Fiber Fluidic Reactor.

Publications

High Throughput Preparation of Poly(Lactic-Co-Glycolic Acid) Nanoparticles Using Fiber Fluidic Reactor.

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