Oral delivery of camptothecin using cyclodextrin/poly(anhydride) nanoparticles

Area of Science:

• Nanotechnology
• Drug Delivery
• Oncology

Background:

• Camptothecin (CPT) exhibits potent anticancer activity but faces clinical limitations due to poor solubility and stability.
• Developing effective delivery systems is crucial for CPT's therapeutic potential.

Purpose of the Study:

• To overcome CPT's limitations by formulating it into poly(anhydride) nanoparticles combined with cyclodextrins.
• To evaluate the physicochemical properties, drug release, and pharmacokinetic profile of these novel nanoparticles.

Main Methods:

• Preparation of CPT-loaded nanoparticles (HPCD-NP) using poly(anhydride) and 2-hydroxypropyl-β-cyclodextrin.
• Assessment of nanoparticle size, drug payload, and in vitro drug release under simulated gastric and intestinal conditions.
• Pharmacokinetic studies in animals to determine CPT plasma levels, bioavailability, and clearance after oral administration.

Main Results:

• HPCD-NP showed a high drug payload (50μg/mg) and appropriate size (~170nm).
• Drug release was minimal in gastric conditions but exhibited a burst release followed by zero-order kinetics in intestinal conditions.
• Oral administration of HPCD-NP resulted in significantly higher and sustained CPT plasma levels up to 48 hours, with a 7-fold increase in oral bioavailability and reduced clearance.

Conclusions:

• The developed HPCD-NP system effectively addresses CPT's hydrophobicity and stability issues.
• The enhanced oral bioavailability is attributed to prolonged intestinal residence time, cyclodextrin's stabilizing effect, and an acidic microenvironment promoting the active lactone form.
• This nanoparticle formulation holds promise for improving oral delivery and clinical application of camptothecin.