A Versatile Brij-Linker for One-Step Preparation of Targeted Nanoparticles

Abstract

Background: Most frequently the functionalization of nanoparticles is hampered by time-consuming, sometimes harsh conjugation and purification procedures causing premature drug release and/or degradation. A strategy to circumvent multi-step protocols is to synthesize building blocks with different functionalities and to use mixtures thereof for nanoparticle preparation in one step. Methods: BrijS20 was converted into an amine derivative via a carbamate linkage. The Brij-amine readily reacts with pre-activated carboxyl-containing ligands such as folic acid. The structures of the building blocks were confirmed by different spectroscopic methods and their utility was assessed by one-step preparation and characterization of nanoparticles applying PLGA as a matrix polymer. Results: Nanoparticles were about 200 nm in diameter independent of the composition. Experiments with human folate expressing single cells and monolayer revealed that the nanoparticle building block Brij mediates a “stealth” effect and the Brij-amine-folate a “targeting” effect. As compared to plain nanoparticles, the stealth effect decreased the cell interaction by 13%, but the targeting effect increased the cell interaction by 45% in the monolayer. Moreover, the targeting ligand density and thus the cell association of the nanoparticles is easily fine-tuned by selection of the initial ratio of the building blocks. Conclusions: This strategy might be a first step towards the one-step preparation of nanoparticles with tailored functionalities. Relying on a non-ionic surfactant is a versatile approach as it might be extended to other hydrophobic matrix polymers and promising targeting ligands from the biotech pipeline.

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies

“…This impact was predicted because of the increase in the membrane’s fluidity brought on by more surfactant molecules and the inclusion of more porous holes in the vesicle bilayer, which permits drug leakage and lower EE% values. 27

Figure 2 Response 3D plots for the effect of ( a ): Ceramide IIIB, ( b ): HA amount, ( c ): EA type (Kolliphor RH40 and TPGS), on (2a) EE%, (2b) PS, (2c) PDI, (2d) ZP, and (2e)Drug release Q48 h of Cerosomes.

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“…This impact was predicted because of the increase in the membrane's fluidity brought on by more surfactant molecules and the inclusion of more porous holes in the vesicle bilayer, which permits drug leakage and lower EE% values. 27 Effect of Particle Size, Distribution, and Zeta Potential PS effects of the formulation elements The small particle size of the nanodispersion is essential to forming a system that withstands sedimentation and particle aggregation. Furthermore, the particle size of the nanosystem may affect the degree of skin permeability and medicine retention.…”

Improving Cancer Targeting: A Study on the Effect of Dual-Ligand Density on Targeting of Cells Having Differential Expression of Target Biomarkers

“…With regards to the H:A molar ratio, an optimum was observed at 0.5 for most F:A ratios. Further increase in ligand density yielded lower cellular targeting, likely due to steric crowding of surface ligands restricting interactions with target receptors [15,[51][52][53].…”

“…Cellular targeting increased with increasing H:A molar ratio up to a maximum at a ratio of 0.75 beyond which it again decreased. Improved targeting with increasing ligand density is likely due to HA-CD44 mediated endocytosis while its decrease at higher ligand density could be due to steric crowding [15,[51][52][53].…”

“…A too-high ligand density can promote surface adsorption of proteins, which can lead to nanoparticle clearance by the immune system [14]. Optimization of ligand density is, therefore, necessary to improve cancer cell targeting and limit non-specific interactions [15].…”