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New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB) Stabilized Poly(Lactic-co-Glycolic Acid) (PLGA) Nanoparticles.

Gossmann R, Langer K, Mulac D - PLoS ONE (2015)

Bottom Line: Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability.Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential.In conclusion this study offers a closer and critical point of view on preparation, in vitro and analytical evaluation of DMAB-stabilized PLGA nanoparticles for the physiological use.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstraße 48, 48149, Münster, Germany.

ABSTRACT
Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB), in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA) and polyethylene glycol (PEG) modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to a lower cytotoxic activity against Caco-2 cells. In conclusion this study offers a closer and critical point of view on preparation, in vitro and analytical evaluation of DMAB-stabilized PLGA nanoparticles for the physiological use.

No MeSH data available.


Evaluation of intracellular localization by fluorescence microscopy.Fluorescence visualization of nanoparticle formulations in Caco-2 cells: (A) control, (B) PLGA-DMAB-NP, (C) PLGA-DMAB-PVA-NP and (D) PLGA-DMAB-PEG-NP. Cell nuclei were stained with DAPI, membranes with WGA AlexaFluor 350. Nanoparticles are visualized due to incorporated fluorescence dye Lumogen F Red 305.
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pone.0127532.g003: Evaluation of intracellular localization by fluorescence microscopy.Fluorescence visualization of nanoparticle formulations in Caco-2 cells: (A) control, (B) PLGA-DMAB-NP, (C) PLGA-DMAB-PVA-NP and (D) PLGA-DMAB-PEG-NP. Cell nuclei were stained with DAPI, membranes with WGA AlexaFluor 350. Nanoparticles are visualized due to incorporated fluorescence dye Lumogen F Red 305.

Mentions: In the next step the ability of the nanocarriers to enter Caco-2 cells was examined by incubation with Wheat germ agglutinin AlexaFluor 350 and DAPI in the presence of the various dye-loaded NP formulations. Fig 3 illustrates that aggregates of unmodified PLGA-DMAB-NP adhere to the cell surface and could not be removed by repetitive washing steps. In contrast, the modified PLGA-DMAB-PVA-NP and PLGA-DMAB-PEG-NP did not aggregate and were internalized by the Caco-2 cells, therefore resulting in a high cellular uptake.


New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB) Stabilized Poly(Lactic-co-Glycolic Acid) (PLGA) Nanoparticles.

Gossmann R, Langer K, Mulac D - PLoS ONE (2015)

Evaluation of intracellular localization by fluorescence microscopy.Fluorescence visualization of nanoparticle formulations in Caco-2 cells: (A) control, (B) PLGA-DMAB-NP, (C) PLGA-DMAB-PVA-NP and (D) PLGA-DMAB-PEG-NP. Cell nuclei were stained with DAPI, membranes with WGA AlexaFluor 350. Nanoparticles are visualized due to incorporated fluorescence dye Lumogen F Red 305.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493066&req=5

pone.0127532.g003: Evaluation of intracellular localization by fluorescence microscopy.Fluorescence visualization of nanoparticle formulations in Caco-2 cells: (A) control, (B) PLGA-DMAB-NP, (C) PLGA-DMAB-PVA-NP and (D) PLGA-DMAB-PEG-NP. Cell nuclei were stained with DAPI, membranes with WGA AlexaFluor 350. Nanoparticles are visualized due to incorporated fluorescence dye Lumogen F Red 305.
Mentions: In the next step the ability of the nanocarriers to enter Caco-2 cells was examined by incubation with Wheat germ agglutinin AlexaFluor 350 and DAPI in the presence of the various dye-loaded NP formulations. Fig 3 illustrates that aggregates of unmodified PLGA-DMAB-NP adhere to the cell surface and could not be removed by repetitive washing steps. In contrast, the modified PLGA-DMAB-PVA-NP and PLGA-DMAB-PEG-NP did not aggregate and were internalized by the Caco-2 cells, therefore resulting in a high cellular uptake.

Bottom Line: Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability.Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential.In conclusion this study offers a closer and critical point of view on preparation, in vitro and analytical evaluation of DMAB-stabilized PLGA nanoparticles for the physiological use.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstraße 48, 48149, Münster, Germany.

ABSTRACT
Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB), in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA) and polyethylene glycol (PEG) modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to a lower cytotoxic activity against Caco-2 cells. In conclusion this study offers a closer and critical point of view on preparation, in vitro and analytical evaluation of DMAB-stabilized PLGA nanoparticles for the physiological use.

No MeSH data available.