Abstract
Background: Irinotecan, a topoisomerase I inhibitor, is widely employed in the management of colorectal, pancreatic, and lung malignancies. Its clinical utility is, however, constrained by rapid plasma clearance, conversion to an inactive carboxylate species at physiological pH, and dose-limiting gastrointestinal toxicity. Liposomal encapsulation offers a rational strategy to address these limitations by prolonging systemic circulation, protecting the drug from hydrolytic degradation, and exploiting passive tumor targeting via the enhanced permeability and retention (EPR) effect.
Objective: The present study aimed to fabricate irinotecan-loaded liposomes using the thin-film hydration method, optimize lipid composition with respect to the phosphatidylcholine-to-cholesterol ratio, and comprehensively characterize the resulting nanocarriers for physicochemical attributes, in vitro drug release behavior, release kinetics, and short-term storage stability.
Methods: Eight formulations (F1–F8) were prepared by systematically varying the cholesterol content from 100 to 450 mg while keeping the phosphatidylcholine concentration constant at 200 mg. Vesicles were characterized for particle size, polydispersity index (PDI), zeta potential, and percentage entrapment efficiency (%EE). In vitro drug release was assessed over eight hours using Franz diffusion cells with a cellulose acetate membrane. Release kinetics were modeled using zero-order, first-order, Higuchi, and Korsmeyer–Peppas equations. Formulation morphology was examined by scanning electron microscopy, and drug–excipient compatibility was confirmed by Fourier-transform infrared spectroscopy. Accelerated stability was evaluated at 25°C/60% RH, 30°C/75% RH, and 40°C/75% RH over three months.
Results: The optimized formulation F5 (PC: cholesterol = 200:300 mg) achieved the smallest mean particle size (118 ± 4 nm), a narrow size distribution (PDI = 0.12), a highly negative zeta potential (−48.6 ± 1.3 mV), and the highest encapsulation efficiency (92.1 ± 1.5%). Cumulative drug release over eight hours reached 98.42% with a sustained profile devoid of an initial burst. Release followed first-order kinetics with a Korsmeyer–Peppas exponent of 0.60, indicative of non-Fickian diffusion. SEM confirmed a spherical vesicle morphology. FTIR analysis revealed no new or missing peaks, confirming physicochemical compatibility. The formulation remained stable across all storage conditions, retaining more than 95% release capacity after three months.
Conclusion: The thin-film hydration method yielded stable irinotecan-loaded liposomes with favorable physicochemical properties and a controlled release profile. These nanocarriers hold significant promise for targeted oncological therapy, with the potential to reduce dosing frequency and systemic adverse effects. Further in vivo pharmacokinetic and efficacy studies are warranted to advance the formulation toward clinical evaluation.