Oral self-emulsifying nanoemulsion systems for enhancing dissolution, bioavailability and anticancer effects of camptothecin
This research aimed to prepare a camptothecin (CPT) loaded self nano emulsifying drug delivery system (SNEDDS) that would improve the oral therapeutic efficacy of CPT. 32 full factorial design was employed, and the effect of the amount of oil (X1) and surfactant mixture (X2) was systematically investigated on percentage transmittance (Y1), self-emulsification time (Y2), and percentage cumulative drug release (Y1). Pseudo-ternary phase diagrams were constructed at different km values (1, 2, and 3). In total, 13 experimental runs (LF–1 to LF–13) were prepared at km = 3, evaluated, and converted to solid free-flowing granules (S–SNEDDS) using neusilin® US2. LF–10 comprising 12.5% omega oil and 40% cremophor-RH40 and labrafil-M2125 had nanosizing (<200 nm), high % transmittance (98.42 ± 1.82%), and lower self-emulsification time (21 ± 0.38 Sec). Nano-sized droplets were spherical, as revealed by the TEM study.
Highlights
• Camptothecin (CPT) loaded self nanoemulsifying drug delivery system was prepared.
• Formulation optimization was done by 32 factorial design.
• Amorphous state and molecular dispersion of CPT in SNEDDS was observed.
• CPT-SNEDDS significantly inhibited the proliferation of BEWO placental cancer cells.
• 17-folds increase in bioavailability compared to plain CPT was achieved.
FT-IR spectra showed no incompatibilities, whereas DSC and XRD results confirmed CPT’s amorphous state and molecular dispersion in SNEDDS. In-vitro dissolution studies demonstrated significant (P < 0.05) improvement in CPT release characteristics from S–SNEDDS (SF–10). in-silico studies confirmed hydrogen bond interaction between an amino group of CPT and neusilin oxygen. S-CPT-10 significantly (P < 0.05) inhibited the proliferation of BEWO placental cancer cells more than CPT. It induced apoptosis in cancerous cells, revealed by DAPI, Annexin-V/PI staining, and mitochondrial potential measurement. Remarkably, oral administration of CPT–SNEDDS resulted in a 17-fold increase in bioavailability compared to plain CPT. Thus, SNEDDS could be utilized as a potential carrier for CPT delivery.
Sunil T. Galatage, Rahul Trivedi, Durgacharan A. Bhagwat, Oral self-emulsifying nanoemulsion systems for enhancing dissolution, bioavailability and anticancer effects of camptothecin, Journal of Drug Delivery Science and Technology,
2022, 103929, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2022.103929.