Effect of different molecular weight PLGA on flurbiprofen nanoparticles: formulation, characterization, cytotoxicity, and in vivo anti-inflammatory effect by using HET-CAM assay

Abstract

Objective: The effect of polymers used in nanoparticle (NP) production on the formulation properties is one of the few studied issues. Therefore, this study aims to formulate flurbiprofen (FLB) loaded NPs with different molecular weight (M_w) poly lactic-co-glycolic acid (PLGA) and investigate the effect of M_w on NP character. One of the most important objectives is to provide a high anti-inflammatory effect with a low dose and the anti-inflammatory efficacy of the selected optimal formulation is to be determined by in vivo hen’s egg test on Chorioallantoic Membrane (HET-CAM) analysis that a new, popular and in vivo animal experiment alternative method.

Significance: To determine the anti-inflammatory efficacy of the optimum formulation by HET-CAM analysis. To the best of our knowledge, this is the first report on the in vivo anti-inflammatory evaluation of FLB-loaded PLGA NP using the in vivo HET-CAM assay.

Methods: Blank and FLB-loaded PLGA NPs were prepared using a nanoprecipitation technique. The cell viability test for all formulation was performed with MTT in the NIH-3T3 mouse embryonic fibroblast cell line. The anti-inflammatory activity of optimum formulation (A₆) was examined using the in vivo HET-CAM assay.

Results: The particle sizes (PSs) of the FLB-loaded PLGA NPs were between 175 and 198 nm. The encapsulation efficiency (EE%) was a range of 82–93%. In vitro release of NPs showed extended-release up to 144 h. The release kinetics were fitted to the Peppas–Sahlin and Weibull models. The results showed that PS, PDI, EE%, and release rates of NPs were directly related to the M_w of PLGA. There is no statistically significant difference in cell viability study was observed between blank and FLB-loaded PLGA NPs. The in vivo anti-inflammatory activity results indicated that A₆ coded formulation was showed significantly good anti-inflammatory potential at low dose.

Conclusions: It could be concluded that FLB-loaded NPs seem to be a promising extended-release drug delivery system for oral administration with a low dose and high efficiency.

Keywords:

• Flurbiprofen
• PLGA
• Resomer RG 502 H
• Resomer RG 503 H
• Resomer RG 504 H
• nanoparticle
• cytotoxicity
• anti-inflammatory
• in vivo HET-CAM assay

Acknowledgments

The authors would also like to thank to Anadolu University, Faculty of Pharmacy, DOPNALAB for FT-IR analysis. We would like to thank specially Mrs. Emine Kırcalı Kocabaş from Has Tavuk Company for providing the fertilized hen eggs. The authors would also like to thank corresponding authors father A. Nurol Öztürk for providing DSC cells.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research work was supported by a grant from the Anadolu University Scientific Research Project Foundation [Project number 1805S212]. SANOVEL (İstanbul, Turkey) for providing flurbiprofen.