Design and biological activity of novel stealth polymeric lipid nanoparticles for enhanced delivery of hydrophobic photodynamic therapy drugs

Abstract

Advances in in vivo stability and preferential tumor uptake of cancer nanomedicine are warranted for effective chemotherapy. Here, we describe a novel nanoformulation using an unconventional polymeric tubule-forming phospholipid, DCPC. We report that DCPC transitions to stable vesicles (LNPs) in the presence of PEGylated lipid (DSPE-PEG2000); the resulting DCPC:DSPE-PEG2000 LNPs efficiently included a hydrophobic PDT drug, HPPH. Remarkably, these LNPs incorporated unusually high DSPE-PEG2000 concentrations; LNP-HPPH and LNP-HPPH (10 & 20 mol% PEGylated lipid, respectively) exhibited >90% serum stability at 37 °C. Increased PEGylation in the LNPs correlated with enhanced tumor accumulation in intravenously injected HT29 tumor mouse xenographs. Colon-26 bearing BALB/c mice, intravenously injected with LNP-HPPH showed superior PDT efficacy and animal survival (no tumor recurrence up to 100 days) as compared to a formulation currently used in clinical trials. Taken together, we present a simple stealth binary lipid nanosystem with enhanced efficiency of tumor accumulation and superior therapeutic efficacy.

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

“…Although PEG has been considered for many years as the gold standard of stealth-inducing materials and is still used for the production of stealth drug delivery systems (Pasut et al, 2015;Chen et al, 2018;Cui et al, 2018;Viard et al, 2018;Zhong et al, 2019), many of its limitation have recently been evidenced. First, PEG does not only hinder the interactions of NPs with phagocytic cells responsible for their quick clearance, but also reduce the efficiency of uptake by the target cells NPs are directed against (Zhang et al, 2015).…”

Poly(3-hydroxybutyrate-CO-3-hydroxyvalerate) PHBHV biocompatible nanocarriers for 5-FU delivery targeting colorectal cancer

“…Characterized by nanosized dimensions and engineered specificity, nanomedicines can be tailored to include multiple component drugs per se combined in customized drug delivery systems addressing the complicated needs of chemotherapy. Development of colloidal nanoparticles consisting of polymers, dendrimers, lipids, as well as organometallic and carbon-based materials, with sizes less than a micron for anticancer drug targeting contemplates using carriers able to both bind and easily release their load in a controlled manner (Torchilin, 2010; Bartoş et al., 2016; Quinn et al., 2017; Hunter & Moghimi, 2017; Kuskov et al., 2017; Viard et al., 2018; Zhao & Stenzel, 2018; Taghizadehghalehjoughi et al., 2018; Luss et al., 2018). Polymer nanocarriers, in particular, have been at the focal point of targeted and controlled drug delivery studies since their tunable chemistry allows to adjust biocompatibility, toxicity, size, surface chemistry, and stability in biological systems with the aim to improve the efficacy of drugs with physicochemical (e.g.…”

Thermotropic effects of PEGylated lipids on the stability of HPPH-encapsulated lipid nanoparticles (LNP)

“…The diacetylene bonds present in the tail chains of the vesicles or liposomes upon photoactivation changes conformation (from cis to trans) to release the encapsulated content to the target location [ 29 , 43 – 46 ]. Our recent work involving PEGylated-DSPE lipids along with DC 8,9 PC, resulted in formation of stable vesicular lipid nanoparticles (LNP’s) in the nanometer size range of 99–110 nm [ 47 ]. This unique lipid packing was found to be dependent on the mole ratios of the pegylated lipids (DSPE-PEG), with optimal concentrations of up to 20 mol%.…”

“…These liposomal carriers and HPPH demonstrated faster skin clearance and deeper tumor penetration at lower dosage rates as opposed to various other FDA approved photosensitizers [ 48 – 50 ] in addition to their stability at room temperatures. The HPPH-loaded LNPs exhibited remarkable PDT efficiency and animal survival rates during the clinical trials [ 47 ], with potential biomedical applications in enhanced drug delivery [ 47 , 51 ].…”