Biodegradable nanoparticles mimicking platelet binding as a targeted and controlled drug delivery system

Abstract

This research aims to develop targeted nanoparticles as drug carriers to the injured arterial wall under fluid shear stress by mimicking the natural binding ability of platelets via interactions of glycoprotein Ib-alpha (GP Ibα) of platelets with P-selectin of damaged endothelial cells (ECs) and/or with von Willebrand factor (vWF) of the subendothelium. Drug-loaded poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles were formulated using a standard emulsion method and conjugated with glycocalicin, the external fraction of platelet GPIbα, via carbodiimide chemistry. Surface-coated and cellular uptake studies in ECs showed that conjugation of PLGA nanoparticles with GPIb significantly increased nanoparticle adhesion to P-selectin- and vWF-coated surfaces as well as nanoparticle uptake by activated ECs under fluid shear stresses. In addition, effects of nanoparticle size and shear stress on adhesion efficiency were characterized through parallel flow chamber studies. The observed decrease in bound nanoparticle density with increased particle sizes and shear stresses is also explained through a computational model. Our results demonstrate that the GPIb-conjugated PLGA nanoparticles can be used as a targeted and controlled drug delivery system under flow conditions at the site of vascular injury.

Effects of Biomimetic Shear Stress by Self-Assembled Gelatin Oleic Nanoparticles Containing Paclitaxel on the Behavior of Cancer Cell Lines in a Microfluidic System

“…Considering that nanoparticles are biodegradable, poly(lactic-co-glycolic acid) nanoparticles decreased targeting to epithelial or endothelial cells under shear stress [9,10]. Biodegradable liposomal nanoparticles showed different delivery efficiencies depending on their charges.…”

“…Few studies have evaluated the interactions between nanoparticles and cells within a biomimetic dynamic environment. Previous studies have shown decreased targeting of poly(lactic-co-glycolic acid)-based nanoparticles [9,10] and increased delivery efficiency of liposome and polystyrene nanoparticles with increasing shear stress [11][12][13]. Other studies determined the charges of nanoparticles and found that the interaction of positively charged nanoparticles with myoblast cells was enhanced in the presence of shear stress, whereas negatively charged nanoparticles showed decreased interactions [14].…”

Encapsulation of human serum albumin in submicrometer magnetic poly(lactide-co-glycolide) particles as a model system for targeted drug delivery

“…The mole ratio of Fe(II) to Fe(III) had to be close to 1/2. On addition of NH 4 OH, the initially clear yellow solution immediately turned black, indicating the precipitation of Fe 3 O 4 nanoparticles. To ensure oxidation stability of the nanoparticles, Fe 3 O 4 was oxidized with NaClO solution to γ-Fe 2 O 3 that is more stable against oxidation than Fe 3 O 4 .…”

“…Poly(D,L-lactic-co-glycolide) (PLGA) is a biocompatible (non-toxic) and biodegradable material that is FDA approved and often used for preparation of nanoand microparticles (Kona et al [4], Galeska et al [5]). Moreover, it has excellent drug-loading capacity.…”

Interaction between drug delivery vehicles and cells under the effect of shear stress

“…61 Upon injury or under conditions like thrombosis, inflammation, and restenosis, the endothelium is activated and shows an increased expression of EC adhesion molecules such as P-selectin and E-selectin as compared to normal healthy cells. [62][63][64][65] The authors mimicked the natural binding ability of platelets to damaged ECs and functionalized PLGA NPs of several sizes with glycocalicin, the external fraction of glycoprotein Ib-a (GPIba) of platelets, which has high affinity with P-selectin of damaged ECs as well as with the von Willebrand factor of the subendothelium.…”