Encapsulation of paclitaxel into date palm lipid droplets for enhanced brain cancer therapy.

in Scientific reports by Amal Yousfan, Nour Moursel, Abdulsamie Hanano

TLDR

  • Researchers developed a novel delivery method using lipid droplets from palm seeds and mouse liver to improve the delivery of paclitaxel to brain tumors, enhancing its anticancer efficacy and overcoming solubility and toxicity limitations.

Abstract

Paclitaxel, a powerful anticancer drug, is limited by its poor water solubility and systemic toxicity, which hinder its effectiveness against aggressive brain tumors. This study aims to overcome these challenges by exploring novel intranasal delivery methods using lipid droplets (LDs) derived from date palm seeds (DPLDs) and mouse liver (MLLDs). The anticancer efficacy of PTX was evaluated using a comparative intranasal delivery approach. The lipid droplets were fractionated, and their physicochemical and biochemical properties were assessed. Our results showed that both DPLDs and MLLDs were spherical, with average diameters of 257 ± 36 nm and 416 ± 83 nm, respectively, and contained oil-rich cores of 392.5 and 612.4 mg mL. The MLLDs displayed a distinct lipid profile with low triglyceride content and high monoglyceride and diglyceride content. Conversely, the DPLDs primarily consisted of triglycerides, with stable granularity at around 83% and 79% for MLLDs and DPLDs, respectively. Both lipid droplets showed high encapsulation efficiencies, reaching 48.6 ± 3.2% and 45.4 ± 2.4% for MLLDs and DPLDs, respectively, after 4 h of incubation. The bio-distribution kinetics of paclitaxel post-intranasal administration demonstrated lower plasma paclitaxel levels in formulations compared to free paclitaxel. Notably, the accumulation of paclitaxel in the brain was significantly higher for paclitaxel-DPLD at early time points, with 1.527 ± 0.1% ID gand 2.4 ± 0.16% ID gat 5 and 30 min, respectively, compared to paclitaxel-MLLD and free paclitaxel. In Conclusion, the study highlights the potential of intranasal DPLD and MLLD formulations for enhanced brain targeting in brain tumor therapy, offering improved paclitaxel delivery and overcoming solubility and toxicity challenges.

Overview

  • The study explores novel intranasal delivery methods using lipid droplets derived from date palm seeds (DPLDs) and mouse liver (MLLDs) to overcome the challenges of paclitaxel's poor water solubility and systemic toxicity.
  • The study aims to evaluate the anticancer efficacy of paclitaxel using a comparative intranasal delivery approach and assess the physicochemical and biochemical properties of the lipid droplets.
  • The study primarily focuses on determining the potential of intranasal DPLD and MLLD formulations for enhanced brain targeting in brain tumor therapy, improving paclitaxel delivery and overcoming its limitations.

Comparative Analysis & Findings

  • Both DPLDs and MLLDs showed spherical shapes with average diameters of 257 ± 36 nm and 416 ± 83 nm, respectively.
  • The MLLDs displayed a distinct lipid profile with low triglyceride content and high monoglyceride and diglyceride content, whereas DPLDs primarily consisted of triglycerides.
  • The bio-distribution kinetics of paclitaxel post-intranasal administration demonstrated lower plasma paclitaxel levels in formulations compared to free paclitaxel, with a significantly higher accumulation of paclitaxel in the brain for paclitaxel-DPLD at early time points.

Implications and Future Directions

  • The study highlights the potential of intranasal DPLD and MLLD formulations for enhanced brain targeting in brain tumor therapy, offering improved paclitaxel delivery and overcoming solubility and toxicity challenges.
  • Future studies can explore the potential of these formulations in combination with other therapeutic agents or strategies to further enhance their efficacy in brain tumor therapy.
  • The study can also investigate the potential of DPLDs and MLLDs in delivering other hydrophobic drugs, expanding their therapeutic applications.
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