GPIIb/IIIa Receptor Targeted Rutin Loaded Liposomes for Site-Specific Antithrombotic Effect

Abstract

Rutin (RUT) is a flavonoid obtained from a natural source and is reported for antithrombotic potential, but its delivery remains challenging because of its poor solubility and bioavailability. In this research, we have fabricated novel rutin loaded liposomes (RUT-LIPO, nontargeted), liposomes conjugated with RGD peptide (RGD-RUT-LIPO, targeted), and abciximab (ABX-RUT-LIPO, targeted) by ethanol injection method. The particle size, ζ potential, and morphology of prepared liposomes were analyzed by using DLS, SEM, and TEM techniques. The conjugation of targeting moiety on the surface of targeted liposomes was confirmed by XPS analysis and Bradford assay. In vitro assessment such as blood clot assay, aPTT assay, PT assay, and platelet aggregation analysis was performed using human blood which showed the superior antithrombotic potential of ABX-RUT-LIPO and RGD-RUT-LIPO liposomes. The clot targeting efficiency was evaluated by in vitro imaging and confocal laser scanning microscopy. A significant (P < 0.05) rise in the affinity of targeted liposomes toward activated platelets was demonstrated that revealed their remarkable potential in inhibiting thrombus formation. Furthermore, an in vivo study executed on Sprague Dawley rats (FeCl3 model) demonstrated improved antithrombotic activity of RGD-RUT-LIPO and ABX-RUT-LIPO compared with pure drug. The pharmacokinetic study performed on rats demonstrates the increase in bioavailability when administered as liposomal formulation as compared to RUT. Moreover, the tail bleeding assay and clotting time study (Swiss Albino mice) indicated a better antithrombotic efficacy of targeted liposomes than control preparations. Additionally, biocompatibility of liposomal formulations was determined by an in vitro hemolysis study and cytotoxicity assay, which showed that they were hemocompatible and safe for human use. A histopathology study on rats suggested no severe toxicity of prepared liposomal formulations. Thus, RUT encapsulated nontargeted and targeted liposomes exhibited superior antithrombotic potential over RUT and could be used as a promising carrier for future use.

Nattokinase Encapsulated Nanomedicine for Targeted Thrombolysis: Development, Improved in Vivo Thrombolytic Effects, and Ultrasound/Photoacoustic Imaging

“…The in vitro efficiency of clot targeting was assessed by using ImageJ software to quantify the percentage of green channels in the resulting CLSM images of interacted platelets. ImageJ was used to convert the pictures to white and black binary pictures, and the dark areas were quantified to represent the intensity of the green channel in CLSM images, which measures the affinities of C6-LS, C6-RGD-LS, and C6-AM-LS toward activated platelets. , …”

“…ImageJ was used to convert the pictures to white and black binary pictures, and the dark areas were quantified to represent the intensity of the green channel in CLSM images, which measures the affinities of C6-LS, C6-RGD-LS, and C6-AM-LS toward activated platelets. 48,49 2.4.7. In Vitro Fibrinolysis by Confocal Microscopy.…”

Modulation of redox-sensitive transcription factors with polyphenols as pathogenetically grounded approach in therapy of systemic inflammatory response

“…This technique enables polyphenolic compounds to easily pass through the intestinal barrier and enter the bloodstream [ 155 ]. The creation of liposomes loaded with polyphenols and their conjugation with specific proteins can further increase the bioavailability and selectivity of polyphenolic compounds [ 156 ]. In addition, the formation of phospholipid-polyphenol complexes can significantly enhance the solubility of polyphenols in water.…”