Tailoring the supramolecular structure of amphiphilic glycopolypeptide analogue toward liver targeted drug delivery systems

Abstract

Amphiphilic glycopolypeptide analogues have harboured great importance in the development of targeted drug delivery systems. In this study, lactosylated pullulan-graft-arginine dendrons (LP-g-G3P) was synthesized using Huisgen azide-alkyne 1,3-dipolar cycloaddition between lactosylated pullulan and generation 3 arginine dendrons bearing Pbf and Boc groups on the periphery. Hydrophilic lactosylated pullulan was selected for amphiphilic modification, aiming at specific lectin recognition. Macromolecular structure of LP-g-G3P combined alkyl, aromatic, and peptide dendritic hydrophobic moieties and was able to self-assemble spontaneously into core-shell nanoarchitectures with small particle sizes and low polydispersity in the aqueous media, which was confirmed by CAC, DLS and TEM. Furthermore, the polyaromatic anticancer drug (doxorubicin, DOX) was selectively encapsulated in the hydrophobic core through multiple interactions with the dendrons, including π-π interactions, hydrogen bonding and hydrophobic interactions. Such multiple interactions had the merits of enhanced drug loading capacity (16.89±2.41%), good stability against dilution, and excellent sustained release property. The cell viability assay presented that LP-g-G3P nanoparticles had an excellent biocompatibility both in the normal and tumor cells. Moreover, LP-g-G3P/DOX nanoparticles could be effectively internalized into the hepatoma carcinoma cells and dramatically inhibited cell proliferation. Thus, this approach paves the way to develop amphiphilic and biofunctional glycopolypeptide-based drug delivery systems.

Therapeutics Potential of Polysaccharide Based Nanocarriers: A Review

“…Chronic effects refer to the long-term pathological effects of PNPs that develop over time (Debasish Saha, Sugam Kumar et al, 2020). These can include accumulation of PNPs in vital organs, Geno toxicity, and carcinogenicity (Aisha Roshan Mohamed Wali et al, 2017).…”

“…The specific pathological effects of PNPs depend on several factors such as their size, surface charge, surface chemistry, and mode of administration (Debasish Saha, Sugam Kumar et al, 2020). For instance, positively charged PNPs tend to induce higher levels of inflammation and oxidative stress compared to negatively charged or neutral PNPs (Aisha Roshan Mohamed Wali et al, 2017). Similarly, larger PNPs tend to accumulate in the liver and spleen, while smaller PNPs tend to accumulate in the kidneys (Rohollah Sadeghi, Laleh Mehryar et al, 2017).…”

“…To mitigate the potential pathological effects of PNPs, researchers are exploring various strategies such as surface modification, co-administration of antioxidants, and use of biodegradable polymers (Aisha Roshan Mohamed Wali et al, 2017). These strategies aim to improve the biocompatibility and safety profile of PNPs for drug delivery applications (Debasish Saha, Sugam Kumar et al, 2017).…”

Targeting Groups Employed in Selective Dendrons and Dendrimers

“…DOX was encapsulated in LP-g-G3P through multiple interactions, was internalized into the hepatoma carcinoma cells, inhibiting cell proliferation. This type of targeted dendrimer showed to be a promising directed drug delivery system [68].…”