Albumin-based nanoparticles encapsulating SN-38 demonstrate superior antitumor efficacy compared to irinotecan

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery

Background:

• SN-38, an active metabolite of irinotecan, has limited solubility, hindering effective chemotherapy formulation.
• Current polymer-SN-38 drug conjugates face challenges with complex synthesis and low drug loading (1-5% w/w).
• These limitations impede large-scale production and clinical translation of SN-38-based therapies.

Purpose of the Study:

• To develop an efficient SN-38 formulation strategy overcoming solubility and loading challenges.
• To utilize the reversible lactone-carboxylate equilibrium of SN-38 for simplified encapsulation.
• To enhance the therapeutic potential of SN-38 for broad-spectrum chemotherapy.

Main Methods:

• SN-38 was converted to its carboxylate form using sodium hydroxide (NaOH) to improve solubility.
• Human serum albumin-polylactic acid (HSA-PLA) nanoparticles were formulated encapsulating SN-38 carboxylate.
• The encapsulated SN-38 was converted back to its lactone form using hydrochloric acid (HCl).
• Drug loading capacity, in vitro cytotoxicity, and in vivo efficacy in tumor-bearing mice were evaluated.

Main Results:

• The encapsulation strategy achieved a significantly higher drug loading capacity of 19% w/w.
• HSA-PLA (SN-38) nanoparticles demonstrated superior in vitro potency with lower IC50 values compared to irinotecan.
• In vivo studies in mice showed enhanced therapeutic efficacy of the HSA-PLA (SN-38) formulation.

Conclusions:

• Encapsulation of SN-38 in HSA-PLA nanoparticles offers a simplified and effective alternative to polymer-drug conjugation.
• This approach significantly enhances drug loading and therapeutic efficacy, improving translational potential.
• The developed formulation presents a promising strategy for SN-38 delivery in broad chemotherapeutic applications.