Cholesterol-based anionic long-circulating cisplatin liposomes with reduced renal toxicity

Area of Science:

• Nanomedicine
• Drug Delivery Systems
• Liposome Technology

Background:

• Cisplatin (CDDP) is a widely used chemotherapy drug, but its clinical application is limited by severe side effects, particularly nephrotoxicity.
• Developing effective drug delivery systems is crucial to enhance CDDP efficacy and minimize toxicity.
• Cholesterol derivatives, such as cholesterol hemisuccinate (CHO-HS) and cholesterol-polyethylene glycol succinate (CHO-PEG), offer potential for modifying liposome properties.

Purpose of the Study:

• To synthesize and characterize cholesterol-anchored derivatives (CHO-HS and CHO-PEG).
• To prepare anionic long-circulating nanoliposomes using these derivatives for cisplatin (CDDP) delivery.
• To evaluate the physicochemical properties, drug loading, in vitro, and in vivo performance of CDDP-loaded nanoliposomes.

Main Methods:

• Synthesis of CHO-HS and CHO-PEG via esterification.
• Preparation of nanoliposomes by incorporating CHO-HS and CHO-PEG with DSPC at various ratios.
• Characterization using FTIR, (1)H NMR, Dynamic Light Scattering (DLS), and Transmission Electron Microscopy (TEM).
• Evaluation of CDDP encapsulation efficiency, loading efficiency, in vitro drug release, in vitro cytotoxicity, and in vivo distribution.

Main Results:

• Synthesized CHO-HS and CHO-PEG were successfully characterized.
• Nanoliposomes exhibited nanosizes around 100 nm, appropriate zeta potentials (-39.7 mV to -3.18 mV), and good physical stability over 28 days.
• CDDP encapsulation percentage ranged from 43-94% and loading efficiency from 7.5-29.3%.
• In vitro and in vivo studies demonstrated the potential of these nanoliposomes as effective CDDP carriers.

Conclusions:

• CHO-HS/CHO-PEG nanoliposomes are a viable system for long-circulating cisplatin delivery.
• This formulation shows potential for reducing acute renal toxicity associated with cisplatin.
• These nanoliposomes represent a promising strategy for enhancing cisplatin-based cancer therapy.