Introduction

Paclitaxel is a widely used chemotherapeutic agent indicated in multiple malignancies, including breast, ovarian, lung, and pancreatic cancers. It exerts its anticancer effects by stabilising microtubules, thereby disrupting mitosis and inhibiting cancer cell proliferation.

Despite its clinical utility, paclitaxel is associated with pharmacological limitations, particularly related to its solubility, biodistribution, and toxicity profile. These challenges have driven ongoing research into more effective drug delivery strategies.

Limitations of Conventional Paclitaxel Formulations

Paclitaxel is highly hydrophobic, resulting in poor aqueous solubility. Conventional formulations often require solvents such as Cremophor EL, which are associated with hypersensitivity reactions and other adverse effects (Weiss et al., 1990).

Additionally, non-specific distribution of paclitaxel may lead to:

• Suboptimal accumulation at tumour sites
• Increased exposure to healthy tissues
• Dose-limiting toxicities, including neuropathy and myelosuppression

These limitations highlight the importance of improving drug delivery systems to enhance therapeutic outcomes.

Novel Drug Delivery System: L-PGDS-Based Carrier

Recent research from Osaka Metropolitan University has introduced a novel drug delivery system utilising lipocalin-type prostaglandin D synthase (L-PGDS) as a carrier for paclitaxel (Furuta et al., 2026).

L-PGDS is an endogenous protein known for its ligand-binding capacity, making it a potential candidate for transporting hydrophobic compounds such as paclitaxel.

Key Innovations

1. Enhanced Solubility
   The L-PGDS-based system significantly improved the solubility of paclitaxel (reported up to approximately 3,600-fold), potentially facilitating more efficient systemic delivery.
2. Tumour-Targeting Capability
   The addition of a targeting peptide (CRGDK) enables interaction with neuropilin-1 (NRP-1), a receptor commonly overexpressed in tumour vasculature. This may enhance selective accumulation in tumour tissues.
3. Sustained Pharmacological Activity
   The delivery system demonstrated prolonged drug retention and activity, suggesting potential for improved therapeutic durability.

Preclinical Findings

In breast cancer models, the study reported:

• Conventional paclitaxel reduced tumour growth during active treatment but showed diminished effects after cessation
• The L-PGDS-based delivery system maintained sustained antitumour activity beyond the treatment period
• The targeted formulation (with CRGDK peptide) demonstrated enhanced tumour suppression compared to non-targeted formulations

These findings suggest that improved delivery mechanisms may influence not only drug distribution but also treatment persistence.