Potential Of Star-Shaped Polymeric Nanoparticles Of Poly(Epsilon-Carprolactone) And Poly (Lactic-Co-Glycolic Acid) For Drug Delivery; A Comparative Study With Linear Analogs

Background: Methotrexate (MTX) is a broad-spectrum anti-cancer agent used in a variety of cancers. However, its non-selective toxicity causes serious side effects and, consequently, a novel drug delivery system would be an ideal way to maximize the effectiveness of MTX against tumor tissues. Aim: The objectives of the present study were to prepare and compare the physicochemical properties, drug release, and in vitro cytotoxicity of linear and star-shaped polymeric nanoparticles (NPs) for drug delivery of MTX.Methods: Linear and star-shaped poly(epsilon-carprolactone) (PCL), and poly(lactic-co-glycolic acid) (PLGA) were synthesized by ring-opening polymerization and characterized using H-1 NMR, gel permeation chromatography, and FT-IR techniques. MTX polymeric NPs were prepared by using double emulsion solvent evaporation method and characterized in the case of size, morphology, zeta potential, encapsulation efficiency, loading capacity, and drug release. The anti-proliferative effect of NPs was assessed on B16F10 cells implementing the MTT test.Results: The optimized process and formulation parameters resulted in the homogeneous spherical population of linear and star-shaped PCL NPs with a diameter of 56 and 48 nm, and encapsulation efficiency of 18.59 % and 34.64 % w/w, respectively. The linear and star-shaped PLGA NPs were 73 and 54 nm in diameter, with an encapsulation efficiency of 54.99 % and 86.41 % w/w, respectively. Furthermore, the MTX release studies showed that the cumulative release of MTX in the two star-shaped polymeric NPs was 2 times higher than their linear analogs. Finally, the MTT assay showed that both star-shaped polymeric NPs had higher toxicity compared to the linear ones.Conclusion: Star-shaped PCL and PLGA NPs had better physicochemical properties, so they are preferred for drug delivery of MTX compared to the linear analogs.