Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

MDPI full text link MDPI Free PMC article
Full text links

Actions

Share

.2021 May 1;13(5):646.
doi: 10.3390/pharmaceutics13050646.

Development of In Situ Gelling Meloxicam-Human Serum Albumin Nanoparticle Formulation for Nose-to-Brain Application

Affiliations

Development of In Situ Gelling Meloxicam-Human Serum Albumin Nanoparticle Formulation for Nose-to-Brain Application

Gábor Katona et al. Pharmaceutics..

Abstract

The aim of this study was to develop an intranasal in situ thermo-gelling meloxicam-human serum albumin (MEL-HSA) nanoparticulate formulation applying poloxamer 407 (P407), which can be administered in liquid state into the nostril, and to increase the resistance of the formulation against mucociliary clearance by sol-gel transition on the nasal mucosa, as well as to improve drug absorption. Nanoparticle characterization showed that formulations containing 12-15%w/w P407 met the requirements of intranasal administration. The Z-average (in the range of 180-304 nm), the narrow polydispersity index (PdI, from 0.193 to 0.328), the zeta potential (between -9.4 and -7.0 mV) and the hypotonic osmolality (200-278 mOsmol/L) of MEL-HSA nanoparticles predict enhanced drug absorption through the nasal mucosa. Based on the rheological, muco-adhesion, drug release and permeability studies, the 14%w/w P407 containing formulation (MEL-HSA-P14%) was considered as the optimized formulation, which allows enhanced permeability of MEL through blood-brain barrier-specific lipid fraction. Cell line studies showed no cell damage after 1-h treatment with MEL-HSA-P14% on RPMI 2650 human endothelial cells' moreover, enhanced permeation (four-fold) of MEL from MEL-HSA-P14% was observed in comparison to pure MEL. Overall, MEL-HSA-P14% can be promising for overcoming the challenges of nasal drug delivery.

Keywords: RPMI 2650 nasal epithelial cell; brain PAMPA; muco-adhesion; quality by design; rapid equilibrium dialysis.

PubMed Disclaimer

Conflict of interest statement

Egis Pharmaceuticals Plc. had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Preparation of MEL-HSA-P407.
Figure 2
Figure 2
Interdependence rating amongst QTPPs (A), CQAs (C) and MEL-HSA, MEL-HSA-P407 formulations with the corresponding severity scores for QTPPs (B) and CQAs (D). Abbreviations: H: high, L: low, M: medium.
Figure 3
Figure 3
Effect of the P407 concentration on the gelling temperature (A), gelling time at 37 °C (B), and gel strength (C). Data is presented as means ± SD,n = 5.
Figure 4
Figure 4
Adhesive force (A) and adhesive work (B) of the compositions in various P407 concentrations. Data is presented as means ± SD,n = 5.
Figure 5
Figure 5
FITC-labelled MEL-HSA nanoparticles and their distribution in gel structure containing various concentrations of P407 at 60× magnification.
Figure 6
Figure 6
In vitro dissolution profiles of MEL-HSA-P407 formulations in comparison to starting MEL. Data is presented as means ± SD,n = 5.
Figure 7
Figure 7
Fluxes in PAMPA-BBB permeability study of MEL-HSA-P407 formulations compared to starting MEL. Data is presented as means ± SD,n = 6.
Figure 8
Figure 8
Cell viability of RPMI 2650nasal epithelial cells after a 1-h treatment with MEL, MEL-HSA-P14% formulation, or with their components, measured by impedance. The values are presented as a percentage of the control group (means ± SD,n = 6–12). Statistical analysis: ANOVA and Dunett’s test. ***p < 0.01, compared to the control group. TX-100, Triton X-100 detergent.
Figure 9
Figure 9
Permeability of MEL (2 mg/mL in all samples) and MEL-HSA-P14% nano-formulation across a co-culture model of human RPMI 2650 nasal epithelial cells and vascular endothelial cells (1-h assay). Values are presented as means ± SD,n = 3. ***p < 0.001 significantly different from MEL control.
Figure 10
Figure 10
Transepithelial electrical resistance (TEER) of the co-culture model after a 1-h treatment with MEL and MEL-HSA-P14% (A). Values for paracellular permeability markers fluorescein-labeled dextran (FD10) and Evans blue-labeled albumin (EBA) after a 1-h treatment with MEL and the nano-formulation (B). Values are presented as means ± SD,n = 3. C: control; MEL; MEL-HSA-P14%. *p < 0.05; ***p < 0.001 significantly different from control.
Figure 11
Figure 11
Immunostaining for junctional linker proteins ZO-1 and β-catenin on human RPMI 2650 nasal epithelial cell layers following a 1-h treatment with MEL and MEL-HSA-P14%. The control group (C) received only medium. Red: junctional proteins; blue: cell nuclei. Scale bar: 20 μm.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hoogenboezem E.N., Duvall C.L. Harnessing albumin as a carrier for cancer therapies. Adv. Drug Deliv. Rev. 2018;130:73–89. doi: 10.1016/j.addr.2018.07.011. - DOI - PMC - PubMed
    1. Goverdhan P., Sravanthi A., Mamatha T. Neuroprotective effects of Meloxicam and Selegiline in scopolamine-induced cognitive impairment and oxidative stress. Int. J. Alzheimers Dis. 2012;2012 doi: 10.1155/2012/974013. - DOI - PMC - PubMed
    1. Cimen M.Y.B., Cimen Ö.B., Eskandari G., Sahin G., Erdoǧan C., Atik U. In vivo effects of meloxicam, celecoxib, and ibuprofen on free radical metabolism in human erythrocytes. Drug Chem. Toxicol. 2003;26:169–176. doi: 10.1081/DCT-120022645. - DOI - PubMed
    1. Ianiski F.R., Alves C.B., Ferreira C.F., Rech V.C., Savegnago L., Wilhelm E.A., Luchese C. Meloxicam-loaded nanocapsules as an alternative to improve memory decline in an Alzheimer’s disease model in mice: Involvement of Na+, K+-ATPase. Metab. Brain Dis. 2016;31:793–802. doi: 10.1007/s11011-016-9812-3. - DOI - PubMed
    1. Szabó-Révész P. Modifying the physicochemical properties of NSAIDs for nasal and pulmonary administration. Drug Discov. Today Technol. 2018;27:87–93. doi: 10.1016/j.ddtec.2018.03.002. - DOI - PubMed

LinkOut - more resources

Full text links
MDPI full text link MDPI Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp