Enhanced Drug Delivery into Cell Cytosol via Glycoprotein H-Derived Peptide Conjugated Nanoemulsions

Abstract

The key role of nanocarriers in improving the pharmacological properties of commonly used drugs is recognized worldwide. It is also known that in the development of new effective nanocarriers the use of targeting moieties integrated on their surface is essential. Herein, we propose a nanocarrier based on an oil in water nanoemulsion coated with a membranotropic peptide derived from the glycoprotein H of Herpes simplex virus 1, known as gH625, in order to reduce endolysosomal accumulation and to enhance cytosolic localization. In addition, we show an enhanced anti-inflammatory activity of curcumin, a bioactive compound isolated from the Curcuma longa plant, when loaded into our engineered nanocarriers. This effect is a consequence of a higher uptake combined with a high curcumin preservation exerted by the active nanocapsules compared to control ones. When loaded into our nanocapsules, indeed, curcumin molecules are directly internalized into the cytosol rather than into lysosomes. Further, in order to extend the in vitro experimental setting with a more complex model and to explore the possibility to use our nanocarriers for further biological applications, we tested their performance in a 3D sprouting angiogenesis model. Finally, we show promising preliminary in vivo results by assessing the anti-inflammatory properties of the proposed nanocarrier.

<p>Nano-Encapsulation of Coenzyme Q10 in Secondary and Tertiary Nano-Emulsions for Enhanced Cardioprotection and Hepatoprotection in Human Cardiomyocytes and Hepatocytes During Exposure to Anthracyclines and Trastuzumab</p>

“…It is evident from the morphological analysis, the level of monodispersion of the basic carrier, and the size distributions are corroborated by DLS analysis. Based on the dimensional results of the simple system, a first layer of CT and a second one of HA were deposited above the template of O/W NEs via layer-by-layer technique (LbL) 27 , 39 to obtain secondary and tertiary NEs. Indeed, polymers of opposite charge like CT and HA were held together thanks to electrostatic interactions.…”

Design, Synthesis and Characterization of Novel Co-Polymers Decorated with Peptides for the Selective Nanoparticle Transport across the Cerebral Endothelium

“…Therefore, only a small quantity of drugs are able to cross the cell and reach the brain. In this context, in order to overcome the limitation of TAT in the involvement of the endocytic pathway, we chose gH as CPP, which was widely characterized in previous works [ 11 , 12 , 13 , 14 , 15 ]. gH facilitates NP delivering across the BBB, which leads to a significant higher cellular uptake and crossing.…”

“…Moreover, in the case of metallic platinum ultrasmall NPs, gH partially increases their cytosolic delivery and anti-oxidant properties in Hela cells [ 14 ]. Furthermore, we showed that the peculiar mechanism of the entrance of NPs into the cells can easily be translated to soft matter nano-carriers such as oil/water nano-emulsions to enhance the cytosolic delivery of curcumin [ 15 ].…”

Tunable Release of Curcumin with an In Silico-Supported Approach from Mixtures of Highly Porous PLGA Microparticles

“…The CUR-NE was prepared as previously reported [33,37]. Briefly, 1.2 mg of egg-lecithin (surfactant) was dissolved in 5 mL of soybean oil (oil phase).…”

“…We decided to use curcumin since it is a powerful active substance by itself (ex. anti-inflammatory [33,34], anticancer [33]) and a hydrophobic molecule with a logP value of~3.0, which allows it to be dissolvable in common organic solvents and partially soluble in polar solvents including water [35]. These characteristics are common to many hydrophobic drugs (prostaglandin, doxorubicin) making curcumin an ideal model drug.…”