Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery

Abstract

Background:The synthetic potential chemotherapeutic agent 3-Chloro-4- [(4-methoxyphenyl) amino]furo [2,3-b]quinoline (PK-L4) is an analog of amsacrine. The half-life of PK-L4 is longer than that of amsacrine; however, PK-L4 is difficult to dissolve in aqueous media, which is problematic for administration by intravenous injection. Aims: To utilize solid lipid nanoparticles (SLNs) modified with polyethylene glycol (PEG) to improve the delivery of PK-L4 and investigate its biodistribution behavior after intravenous administration. Results:The particle size of the PK-L4-loaded SLNs was 47.3 nm and the size of the PEGylated form was smaller, at 28 nm. The entrapment efficiency (EE%) of PK-L4 in SLNs with and without PEG showed a high capacity of approximately 100% encapsulation. Results also showed that the amount of PK-L4 released over a prolonged period from SLNs both with and without PEG was comparable to the non-formulated group, with 16.48% and 30.04%, respectively, of the drug being released, which fit a zero-order equation. The half-maximal inhibitory concentration values of PK-L4-loaded SLNs with and those without PEG were significantly reduced by 45%-64% in the human lung carcinoma cell line (A549), 99% in the human breast adenocarcinoma cell line with estrogen receptor (MCF7), and 95% in the human breast adenocarcinoma cell line (MDA-MB-231). The amount of PK-L4 released by SLNs with PEG was significantly higher than that from the PK-L4 solution (P , 0.05). After intravenous bolus of the PK-L4-loaded SLNs with PEG, there was a marked significant difference in half-life alpha (0.136 ± 0.046 hours) when compared with the PK-L4 solution (0.078 ± 0.023 hours); also the area under the curve from zero to infinity did not change in plasma when compared to the PK-L4 solution. This demonstrated that PK-L4-loaded SLNs were rapidly distributed from central areas to tissues and exhibited higher accumulation in specific organs. The highest deposition of PK-L4-loaded SLNs with PEG was found in the lung and spine. Conclusion: Sufficient amounts of PK-L4 were entrapped in the SLNs, and the pharmacokinetic behavior of PK-L4-loaded SLNs was established. This formulation successfully resolved the delivery problem, and the drug was localized in particular organs.

Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol

“…In this work the overall immune-compatibility of PEG NCs was highlighted, proving the absence of toxicity and activation stimuli. Our data may give new insights into the use of PEG coating for NCs and other nanomaterials to be used as highly safe and inert molecule 15 16 68 69 . A contribution was given to improve the knowledge on the absence of immune impact and toxicity of PEG in monocytes, as already reported in literature 18 19 and also in primary human immune cells, total PBMCs and specifically in T cell populations.…”

“…Pluro, Chito and PEG coatings have been successfully used for NC functionalization for many applications 12 13 . PEG has been significantly employed to functionalize several nanomaterials to better deliver different genes and drugs such as camptothecin for the cancer treatment 14 15 16 17 . Controversial studies have been published in literature on the ability of PEG coating to be internalized into cells.…”

EphA2 Targeting Pegylated Nanocarrier Drug Delivery System for Treatment of Lung Cancer

“…ENDDs prolonged the half-life of DIM-P, as shown by pharmacokinetic analysis which was substantiated by imaging of ENDDs in vivo . The PEGylation of ENDDs is most likely responsible for this, since its hydrophilicity, flexibility, and neutral charge in biological fluids helps in their dispersion and increases their blood circulation times (37–40). There is no statistically significant difference between NDDs and ENDDs in term of pharmacokinetic half-life (circulation of drug in blood).…”

Theranostic tumor homing nanocarriers for the treatment of lung cancer

“…PCNCs-D prolonged the half-life of DIM-P compared to NCs-D, as shown by pharmacokinetic analysis which was substantiated by imaging of PCNCs-Di in vivo. The PEGylation of PCNCs is most likely responsible for this, since its hydrophilicity, flexibility, and neutral charge in biological fluids helps in their dispersion and increases their blood circulation times 38–40 . PCNCs primarily localized in tumor blood vessels (distinct tumor blood vessel structure is seen in tumor micro-environment, Figure 6).…”